Dissertations / Theses: 'Modern paint'

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Austin, Travis R. "Laminated PAINT." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5462.

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Though we may not perceive it, we are surrounded by material-in-flux. Inert materials degrade and the events that comprise our natural and social environments causally thread into a duration that unifies us in our incomprehension. Sounds reveal ever-present vibrations of the landscape: expressions of the flexuous ground on which we stand.

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Murphy, Gavin. "'The Tropes Out Movement?' : an examination of the work of three English artists dealing with the political conflict in Northern Ireland through the medium of paint." Thesis, University of Ulster, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245807.

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Roche, Linda. "Theatre of painting a structural exploration of the forming of an image through paint : an exegesis submitted to Auckland University of Technology in partial fulfilment of the degree of Master of Arts (Art and Design), 2008 /." Click here to access this resource online, 2008. http://hdl.handle.net/10292/469.

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This studio-based project explores a method of working that assigns agency to paint and process within the medium of painting. Underpinning this exploration is the notion that process driven making could potentially pose as a per formative event. Choreographed yet contingent, the practice investigates the relationship between the potentiality inherent within media and the extent to which this is affected by temporal/ external factors in the determining of outcome. A dialogue between the intentional and the contingent is initiated through a systematic approach that involves manipulation of the constituent elements of paint and the implementation of procedure and protocols as a means to activate conditions of possibility. Central to the research concerns are issues surrounding the ability of media to articulate itself, determine its own temporality and of process and content to operate conterminously. The images produced evidence this investigation as both enquiry and consequence.

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Izzo, Francesca Caterina <1982&gt. "20th century artists' oil paints : a chemical-physical survey." Doctoral thesis, Università Ca' Foscari Venezia, 2011. http://hdl.handle.net/10579/1100.

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Il progetto sviluppato in questa tesi di Dottorato in Scienze chimiche riguarda lo studio di opere di arte moderna e contemporanea con particolare riferimento alle indagini sui materiali e tecnologie usate dagli artisti. Per tale ricerca sono state sviluppate delle tecniche di indagine innovative, specifiche in grado di rilevare non solamente la natura dei materiali utilizzati ma anche il loro comportamento nel tempo. Questa ricerca si è inserita in un progetto internazionale riguardante appunto la conservazione dell’arte contemporanea (20th Century Oil Paint Project, promosso dall'ICN The Netherlands Institute for Cultural Heritage, Amsterdam in collaborazione con il Courtauld Institute of Art, London, ilTate, London e il Getty Conservation Institute, Los Angeles). Il lavoro di tesi ha portato in particolare alla messa a punto di metodologie di studio dei oleosi attraverso l’impiego di tecniche cromatografiche (GC-MS, Py-GC-MS) che hanno consentito di individuare la presenza e il ruolo di alcuni additivi industriali (come gli stearati di alluminio e zinco e l'olio di ricino idrogenato) che fino ad ora non erano stati rilevati in maniera significativa,ma che rivestono un ruolo importante nella produzione industriale dei materiali dell’arte. La ricerca è stata condotta dapprima su campioni pittorici ad olio realizzati in laboratorio utilizzando leganti oleosi, pigmenti, siccativi e additivi impiegati nella moderna produzione industriale di colori ad olio. I film pittorici sono stati analizzati mediante l’uso di svariate tecniche analitiche, tra cui la spettrometria infrarosso in trasformata di Fourier (FT-IR), la spettrofotometria a raggi X (XRF), la Termogravimetria (TG), la Calorimetria Differenziale a Scansione (DSC) e la Gascromatografia abbinata alla Spettrometria di Massa (GC-MS). La parte sperimentale si è poi incentrata sullo studio di colori ad olio (a tubetto) provenienti da collezioni storiche di famose ditte produttrici di colori ad olio (come ad esempio Winsor&Newton, Talens, Old Holland, Maimeri). L’ultima parte della tesi è stata dedicata allo studio di significative opere moderne e contemporanee di artisti quali Lucio Fontana, Jasper Johns, Karel Appel, Willem de Kooning, Salvador Dalì, Henri Matisse, Isabel Lambert-Rawsthorne, Ethel Walker, etc. I risultati, oltre che a chiarire le situazioni sotto indagine, aprono una serie di nuove prospettive su settori finora poco approfonditi nella produzione artistica e tecnologica dell’arte moderna e contemporanea.
The research project developes in PhD research in Chemical Sciences deals with the study of modern and contemporary works of art, focusing on materials and production techniques employed by artists. In this study innovative and specific analytical techniques have been optimised: the survey has been successful not only in detecting the nature of artistic materials used in the 20th century, but also in studying their behaviours over time. Thid PhD researc has been part of an international project concerning the Conservation of Contemporary Art and has lead to the improvement of new methodologies to study proteinaceous and lipidic binding media by using chromatographic techniques (GC-MS, Py-GC-MS, HPLC). These methods have also allowed for the identification and the role of industrial additives (such as aluminium and zinc stearates and hydrogenated castor oil), which had been not fully studied previously. This part of the PhD research has been developed in the Netherlands, in the laboratories of the ICN (The Netherlands Institute for Cultural Heritage, Amsterdam), under the supervision of Dr. Klaas Jan van den Berg and Mr. Ing. Henk van Keulen. The research has been part of the international project called "20th Century Oil Paint Project", carried out at ICN in collaboration with Courtauld Institute of Art, London, Tate, London and Getty Conservation Institute, Los Angeles. The research was initially focused on the study of laboratory-reconstructed oil films, which were prepared with lipidic binders, additives, pigments and driers used by modern oil manufacturers. The films were studied by using several analytical techniques: FT-IR, XRF, TG-DSC and GC-MS. This study has lead to an improvement of analytical methodologies for the study of manufactured oil samples. Furthermore, the research focused on real samples taken from important modern paintings by Lucio Fontana, Jasper Johns, Karel Appel, Willem de Kooning, Salvador Dalì, Henri Matisse, Isabel Lambert-Rawsthorne, Ethel Walker, etc. The obtained results are a further step in the knowledge of materials used in artistic and technological production in Contemporary Art.

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Bezy, Renaud. "Paint out ! : la peinture dans le champ élargi." Thesis, Aix-Marseille, 2020. http://www.theses.fr/2020AIXM0012.

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PAINT OUT ! La peinture dans le champ élargi Cette recherche artistique et théorique procède de l'expérimentation au sens de John Dewey. Elle porte sur les conditions et la possibilité d’une pratique picturale qui excède, déborde le cadre généralement assigné à la peinture : l’exposition mais aussi ses caractéristiques physiques (toile, châssis, pigment). Mon hypothèse est que ce dépassement ne passe pas nécessairement par l’épuisement des formes artistiques dans une logique réductionniste et moderniste de disparition. Bien au contraire, Il s’agit d’envisager la peinture comme une adresse qui fasse saillie dans un champ élargi ouvert à l’installation, à la performance, au film, voire à la relecture plus distanciée d’œuvres picturales. Nourri des réflexions d’auteurs théoriques et convoquant les œuvres d’autres artistes (mais aussi d’architectes, de designers, de cinéastes), la thèse s’articule autour de trois grands groupes de productions personnelles : des peintures installées et performées ; un cycle de films figurant un personnage de peintre intitulé « Les Ballets Barbares » ; et enfin un projet (« La Datcha 2 ») qui fonctionne comme la relecture d'une toile collective peinte en 1969. Le mode d’écriture et d’analyse adopté ici procède de l’exploration, une déambulation au milieu d’éléments hétérogènes : concepts, œuvres, lieux, personnages. Pourtant ce procédé ne saurait s’ériger en système tant il engage intuitions, expérimentations et tâtonnements comme autant de tentatives. Dès lors embarqué sur ce radeau, je pourrais faire mienne cette phrase de Fernand Deligny : « Il ne s’agit pas de méthode, je n’en n’ai jamais eu »
This artistic and theoretical research proceeds from experimentations as developed by John Dewey. It adresses the conditions and the possibilities of a pictorial practice which would exceed, go beyond the framework generally assigned to painting: the exhibition but also its physical characteristics (canvas, stretcher, pigment). My hypothesis is that challenging some of the conventions attached to painting does not necessarily go through the exhaustion of artistic forms in a reductionist and modernist logic of disappearance. On the contrary, the issue here is to consider a practice of painting that would manifest itself in an expanded field, open to installations, performances, films, and even to the practice of distanciation, a rereading of historical pictorial works.Fuelled by the reflections of theoretical authors and addressing the works of other artists (but also architects, designers, filmmakers), the thesis revolves around three major groups of personal artistic productions : installed and performed paintings; a cycle of films depicting a painter character entitled "Les Ballets Barbares"; and finally a project ("La Datcha 2") which functions like the rereading of a collective canvas painted in 1969. The writing process adopted here proceed by exploration, a wandering in the midst of heterogeneous elements: concepts, works, places, characters. However, this process cannot be set up as a system as it involves intuitions, experiments and trial and error as many attempts. Therefore embarked on this raft, I could make mine this sentence of Fernand Deligny: "It is not about method, I never had one"

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Moore, Grace. "Paine, Blake and Hegemony." W&M ScholarWorks, 1996. https://scholarworks.wm.edu/etd/1539626059.

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Thrush, Elizabeth Neely. "Explanatory models of chronic pain." Morgantown, W. Va. : [West Virginia University Libraries], 1999. http://etd.wvu.edu/templates/showETD.cfm?recnum=1030.

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Cascarilla, Elizabeth A. "Chronic Pain-Related Distress & Disability: An Empirical Investigation of a Modern Behavioral Theory of Acceptance of Chronic Pain." University of Akron / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=akron1257472306.

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Natale, Claudia. "Spinal glycinergic neurotransmission in neuropathic pain models." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/25376.

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Disruption to inhibitory neurotransmission is commonly associated with the development of chronic neuropathic pain. However, exactly which aspect of inhibition is affected varies between studies with little consensus on the major contributors. I hypothesised that the different neuropathic pain models used in each study contribute to these discrepancies. Thus, the first part of this thesis focused on the following question: Do different neuropathic pain models produce different physiological changes in the spinal cord dorsal horn? Neuropathic pain is poorly treated with existing analgesics, making the need for novel therapeutics paramount. The glycine transporter 2 (GlyT2) is expressed at inhibitory glycinergic synapses in the spinal cord and novel analgesic compounds targeting it have been developed. The second part of this thesis investigated the cellular actions of one of these novel compounds and asked; How does the novel GlyT2 inhibitor, Oleoyl-D-Lysine, effect glycinergic neurotransmission in the spinal cord dorsal horn? Patch-clamp electrophysiology was used in both projects. In project 1, changes to glycinergic neurotransmission were investigated in chronic constriction injury (CCI) or partial nerve ligation (PNL) models. Both produced similar behavioural outcomes, but vastly different physiological changes. Reduced glycinergic neurotransmission was observed in the PNL model, but not the CCI model. In project 2, Oleoyl-D-Lysine displayed a minor effect on synaptic glycinergic currents, but its predominant effect was on tonic glycinergic currents and produced no detrimental effects on presynaptic glycine supply. Overall, these results suggest that each neuropathic pain model should be considered unique and more research should look into the distinct nociceptive circuits involved for a better understanding of neuropathic pain physiology, as well as to identify more novel therapeutic targets. In addition, the findings suggest that despite Oleoyl-D-Lysine’s glycinergic specific mechanism, it may be effective in treating neuropathic pain caused by different injuries because its main effect is to reduce the excitability of the system not just to enhance glycinergic neurotransmission as was previously hypothesised.

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Lariviere, William R. "The bee venom test : a new tonic-pain test." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=23405.

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The present study describes a new test of tonic pain in rats which can be used as an animal model of persistent pain. In the first experiment, the response to subcutaneous injection of various doses of bee venom into the hind paw of the rat was quantified. The second experiment investigated the effect of morphine and aspirin on the response to an intermediate dose of bee venom. Finally, the third experiment examined the response to concurrent injections of bee venom and formalin. Subcutaneous injection of bee venom produced local inflammation, marked edema, and tonic pain responses. Increasing doses of bee venom produced higher mean pain scores and increased durations of responding. Pain responses lasted up to approximately one hour and the inflammation and edema were virtually gone by 8 hours with the lower doses of bee venom tested and by 2 days with the two highest doses tested. Analgesia was produced by morphine and aspirin, indicating that the bee venom test can be used to test analgesic drugs. Concurrent administration of bee venom and formalin produced responses similar to formalin alone, with an increased duration of responding at higher intensities. The data suggest that the bee venom test is a valid animal model of experimental tonic pain.

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Dehghani, Mohsen. "Cognitive behavioural models of chronic pain & the role of selective attention." Connect to full text, 2003. http://hdl.handle.net/2123/584.

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Thesis (Ph. D.)--University of Sydney, 2004.
Title from title screen (viewed 6 May 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Dept. of Psychology. Degree awarded 2004; thesis submitted 2003. Includes bibliographical references. Also available in print form.

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Schulte, Helène. "Human experimental pain models : methodological & analgesic studies /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-336-1/.

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Abdul, Aziz Che Badariah. "Thalamic nociceptiive processing in rat models of acute inflammatory pain and chronic neuropathic pain." Thesis, University of Nottingham, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410465.

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Nwosu, Lilian Ngozi. "Structural and pain modifications in models of osteoarthritis." Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/30670/.

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Background: Despite the extensive research into the pathophysiology of osteoarthritis (OA), pain still represents a significant unmet clinical need. This thesis explores the effects of a tropomyosin related kinase A receptor (TrkA) inhibitor and an anti-nerve growth factor (NGF) antibody as interventions to modify inflammation, structural pathology and pain behaviour in rat models of OA. Methods: Rat models of OA (monosodium iodoacetate - MIA and medial meniscal transection – MNX) were assessed for pain behaviour and pathology. Effect of interventions on pain behaviour (weight bearing asymmetry and paw withdrawal thresholds) and structural pathology (macroscopic and microscopic scoring of articular surfaces) to include inflammation were assessed using inhibitors of the NGF-TrkA pathway. Pain Data were analysed longitudinally using area under the curve or independently with Kruskal Wallis test followed by Dunns post hoc. Other data were analysed with Kruskal Wallis test followed by Dunns post hoc. Results: The MIA and MNX models all exhibited inflammation and pain behaviour. The MIA and MNX models displayed both macroscopic and microscopic pathology. Following preventive or therapeutic treatment with the tropomyosin receptor kinase (Trk) A inhibitor AR786, pain behaviour was inhibited in both MIA and MNX models. Synovitis was attenuated only in the MIA model. Analgesia was sustained for up to 10 days in the MNX model following AR786 treatment discontinuation. Preventive and therapeutic treatment with the anti–NGF monoclonal antibody M911 did not alter changes to cartilage pathology. Conclusions: Manifestation of pain, inflammation and alterations in knee joint structure are characteristic features of OA models. NGF might contribute to OA pain through the NGF-TrkA pathway. This contribution might be as a result of facilitating nociception, and inflammation. Further investigation into the mechanisms by which NGF contributes to OA pain through the TrkA receptor might increase therapeutic potential for OA chronic pain relief.

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Williams, Amanda Clare de Coetlogon. "Cognitive-behavioural management of chronic pain : models and outcomes." Thesis, King's College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406221.

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Emraja, Ahmed M. M. "Animal models of neuropathic pain after spinal cord injury." Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/4176/.

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Approximately 70% of spinal cord injured patients suffer from pain and it is estimated that in 40-50% of these, the pain is of central neuropathic origin. This pain can be perceived to originate at, or below the level of injury and both evoked and spontaneous pain can occur. Neuropathic pain after spinal cord injury (SCI) is difficult to treat and often poorly controlled by the currently available analgesics so that development of better treatments is an important need. Current ideas about the treatment of SCI pain are that different approaches may be needed to treat the different types of pain (e.g. evoked and spontaneous, at level and below level) as they may have different mechanisms. However, this mechanistic approach to treatment is hampered by a poor understanding of the underlying mechanisms. This in turn depends on development of animal models and pain assessment techniques suitable for mechanistic studies. In this thesis, several rodent SCI models have been investigated using a range of assessment techniques some of which were developed in the course of the study. Contusion injuries at a low thoracic level are currently the most popular model used to investigate central neuropathic pain in rodents. However this model and the assessments used with it are subject to a number of limitations. We therefore began by re-evaluating this model using a relatively severe (200 kdyn) injury since this is indicated in the literature as being necessary for the development of robust signs of neuropathic pain. We found that this model showed robust signs of tactile allodynia and thermal hyperalgesia of the forepaws and in addition by developing new tests, were able to demonstrate cold allodynia and hyperalgesia. Although the hindpaws also showed responses that would normally be interpreted as mechanical allodynia and thermal hyperalgesia, the absence of accompanying supraspinally mediated behaviours (including licking following heat stimuli) indicated that the enhanced responsiveness to these stimuli might not give rise to pain. Further investigation using operant testing supported this idea and tract tracing suggested that this may be due to substantial interruption of ascending nociceptive pathways. Testing over the back at locations confirmed electrophysiologically to involve sensory processing at, above and below the injury level supported the idea that increased sensitivity in this model developed at and above, but not below level. In addition, observations on the forepaws suggested evidence of spontaneous pain which has never been described in SCI models previously and provides an important opportunity for studying the underlying mechanisms. Because the 200 kdyn low thoracic model proved unsuitable for the study of below level pain we next investigated whether a less severe injury at this level would provide a better model. Injuries of 150 kdyn were found to result in most of the same indicators of pain following forelimb testing as were seen following 200 kdyn injuries but all signs were less pronounced, in particular, indicators of evoked pain. Testing over the back led to increased sensitivity below level which had not been evident in the 200 kdyn model, providing an opportunity for below level testing. However, interpretation of hindpaw tests remained equivocal. Because the low thoracic model showed features that suggested forelimb assessments were particularly useful for the assessment of above level pain of different modalities as well as spontaneous pain, we investigated the effect of moving the injury closer to the segments assessed by such tests. Injuries at the T3/T4 level were found to lead to enhancement of all of the behavioural signs seen in the 200 kdyn low thoracic injury animals, especially signs of spontaneous pain. This model may therefore be optimum for the assessment of above/at level pain. The work presented in this thesis provides the clearest and most comprehensive data yet on the utility of models of SCI for the investigation of central neuropathic pain and represents a significant advance in the field. The finding that injuries at low thoracic levels may (depending on injury severity) be unsuitable for assessment of below level pain has implications for previous studies of the mechanisms of post SCI pain, many of which have used exclusively hindlimb assessments in these models. The hope is that an improved understanding of the models used here and an improved ability to investigate different modalities of evoked pain, and in addition spontaneous pain, will enhance the quality of future research in this area and lead to both a better understanding of central neuropathic pain mechanisms and the development of more effective analgesics for this type of pain.

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Huang, Junting. "Investigation of inflammatory mechanisms in models of osteoarthritic pain." Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/28970/.

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Background: Osteoarthritis (OA) is a highly prevalent joint degenerative disorder among the older population. The main symptoms of OA are chronic pain, swelling and stiffness of joint. OA histopathology is characterized by cartilage damage, synovial inflammation and remodelling of subchondral bone. Resolvins are endogenous lipid mediators produced from Ω-3 poly-unsaturated fatty acids (PUFAs) during resolution of inflammation. The main biological functions of resolvins include anti-inflammation and resolution of inflammation. Currently, the emerging anti-nociceptive roles of some resolvins have been reported in various models of pain. However, roles of resolvins and the resolvin receptor system on osteoarthritic pain are unknown. Objectives: This thesis assesses the therapeutic potential of a resolvin precursor on OA pain and investigates the underlying mechanisms of action and resolvin receptor system in OA. Methods: Monosodium iodoacetate (MIA) and medial meniscus transection (MNX) -induced joint damage was used as models of OA pain. 17(R)-HDoHE (300ng/300μl) or vehicle (1% ethanol in saline, 300μl) was acutely or chronically administered at day 14 post model induction and pain behaviour was measured to determine the analgesic effects of the drug in these models. Haematoxylin and eosin (H&E) staining was used to assess joint histopathology. Gene expression of resolvin receptors, inflammatory cytokines and metabolic enzymes were measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in associated tissues from the models and human OA samples. Results: Pain behaviour and joint histopathology were established in both the MIA and MNX models. Expression of chemokine-like receptor 1(ChemR23) was lower in the synovia and higher in the spinal cord in the MIA model. 15-lipoxygenase (15-LOX) was expressed at a lower level in both synovia and spinal cord in the MIA model. Negative correlations were revealed between synovial ChemR23 expression and pain behaviour at both day 14 and 35 in the MIA model. ChemR23 expression in the spinal cord was positively correlated with pain behaviour at day 35 in the MIA model. Expression of formyl peptide receptor 2 (ALX), some inflammatory cytokines and metabolic enzymes was lower in the synovia in the MNX model but expression of 5-lipoxygenase-activating protein (FLAP) was higher. Expression of ALX in the synovia was positively correlated with tumor necrosis factor alfa (TNFα), interleukin 1 beta (IL1β) and cyclooxygenase 2(COX2) but negatively correlated with 5-LOX expression in the MIA model. Expression of ALX in the spinal cord was positively correlated with pain behaviour at day 14 but then the converse was true at day 35. Expression of ALX in the spinal cord was negatively correlated with IL6 in the MIA model. 17(R)HDoHE attenuated pain behaviour in both the MIA and MNX models following acute, chronic and discontinuous administration. Effects of acute administration of 17(R)HDoHE on pain behaviour were associated with an up-regulation in the expression of IL6 and decreased 5-LOX expression in the synovia of MIA model. A trend towards down-regulation of pro-inflammatory cytokines and associated enzymes by 17(R)HDoHE was observed in the acute study in the MIA model. Repeated administration of 17(R)HDoHE produced robust and sustained inhibitory effects on pain behaviour, but no change in joint histopathology. Pain behaviour was attenuated when 17(R)HDoHE was administered but returned to levels seen in vehicle treated rats after 7 days after drug cessation. In human OA samples, expression of ChemR23 was significantly higher than expression of ALX in both synovia and medial tibial plateau. ChemR23 expression was positively correlated with expression of 5-LOX in both synovia and medial tibial plateau and negatively correlated with 15-LOX2 expression in the medial tibial plateau from OA patients. There was a significantly positive correlation between ChemR23 expression and IL6 and 15-LOX1 expression in the medial tibial plateau. In addition, there was a significantly positive correlation between ALX and IL6 and 15-LOX1 expression in both synovia and medial tibial plateau. Expression of ALX, TNFα, IL6, COX2 and 5-LOX in the medial tibial plateau from OA patients was lower, compared to expression in bone from femoral heads obtained from trauma patients. Conclusions: These findings support anti-nociceptive and anti-inflammatory roles of resolvins and provide evidence that resolvins may be potential novel drugs to treat OA pain.

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Legg, Ewen. "Behavioural co-morbidities in rat models of neuropathic pain." Thesis, Imperial College London, 2011. http://hdl.handle.net/10044/1/9070.

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Pain is a complex experience involving both sensory and emotional aspects. Neuropathic pain syndromes, which remain a major area of unmet clinical need, are often associated with behavioural co-morbidities such as anxiety and depression. Recent studies have demonstrated changes in a number of affect-related outcome measures in rodent models of neuropathic pain. The expansion of such outcome measures offers one possible route for the improvement of studies aimed at creating novel therapies for neuropathic pain. Bias reduction through randomisation requires mixed housing of animals with peripheral nerve injuries with non-injured conspecifics. Such mixed housing was shown to alter behaviour in the open field. Therefore, in the following studies treatments were allocated to cage groups as a whole. Anxiety-like behaviour was demonstrated in L5 spinal nerve transected (L5 SNT) rats in a novel dark/light preference test and the utility of this test in detecting efficacious analgesics was investigated. The possible presence of neuropathy-induced depression-like behaviour following L5 SNT was then investigated using the forced swim test. However, animals showed no increase in depression-like behaviour, as measured by time spent immobile in the forced swim test, at either two or three weeks post-neuropathy. Assessment of burrowing behaviour, a novel behavioural outcome measure thought to reflect over all well being in rodents, was then carried out in rats following L5 SNT and partial sciatic nerve ligation. A reduction in burrowing behaviour was demonstrated in both models of neuropathic pain compared to naive animals. The use of novel outcome measures, such as those detailed above, both as outcome measures in drug development and in studies into pathophysiology will improve the quality of studies aimed at creating novel therapies for neuropathic pain.

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Harrison, Dana M. "Realism in Pain: Literary and Social Constructions of Victorian Pain in the Age of Anaesthesia, 1846-1870." Thesis, Temple University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3564812.

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In 1846 and 1847, ether and chloroform were used and celebrated for the first time in Britain and the United States as effective surgical anaesthetics capable of rendering individuals insensible to physical pain. During the same decade, British novels of realism were enjoying increasing cultural authority, dominating readers' attention, and evoking readers' sympathy for numerous social justice issues. This dissertation investigates a previously unanswered question in studies of literature and medicine: how did writers of social realism incorporate realistic descriptions of physical pain, a notoriously difficult sensation to describe, in an era when the very idea of pain's inevitability was challenged by medical developments and when, concurrently, novelists, journalists, and politicians were concerned with humanitarian reforms to recognize traditionally ignored and disadvantaged individuals and groups in pain? By contextualizing the emergence of specific realist novels including works by Elizabeth Gaskell, Charles Reade, William Howard Russell, and Charles Dickens, within larger nonfiction discourses regarding factory reform, prison reform, and war, this dissertation identifies and clarifies how realist authors, who aim to demonstrate general truths about "real life," employed various descriptions of physical pain during this watershed moment in medicine and pain theory, to convince readers of their validity as well as to awaken sympathetic politics among readers.

This study analyzes Gaskell's first industrial novel, Mary Barton (1848), Reade's prison-scandal novel, It is Never Too Late to Mend (1856), Russell's Crimean War correspondence (1850s) and only novel, The Adventures of Doctor Brady (1868), and Dickens's second Bildungsroman, Great Expectations (1861), thereby revealing different strategies utilized by each author representing pain - ranging from subtle to graphic, collective to individualized, urgent to remembered, and destructive to productive. This study shows how audience expectations, political timing, authorial authority, and medical theory influence and are influenced by realist authors writing pain, as they contribute to a cultural consensus that the pain of others is unacceptable and requires attention. These realist authors must, in the end, provide fictionalized accounts of pain, asking readers to act as witnesses and to use their imaginations, in order to inspire sympathy.

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Liman, Suryamin, and 陳明正. "Ketamine on chronic post-ischemia pain (CPIP) model of complex regional pain syndrome (CRPS) type I in Sprague-Dawley (SD) rats." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B45989448.

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Gowler, Peter. "Investigating the role of neurotrophins in the development of pain responses in animal models of joint pain." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/50660/.

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Background: The chronic joint disease osteoarthritis (OA) represents a significant global problem, not only at the present time, but also for the future. Characterised by articular cartilage degeneration, inflammation of the synovium, and subchondral bone changes, it is the chronic pain associated with OA which presents the most serious consequences. There is a clear need to understand the mechanisms under lying chronic joint pain, and to identify novel therapeutic targets. Two targets which may have therapeutic potential are BDNF and cordycepin. Objectives: The objectives of this thesis are two-fold; firstly to establish a slow progressing murine model of OA that is representative of post-traumatic OA, and secondly to investigate peripheral targets which may modulate chronic OA pain. Methods: Surgical destabilisation of the medial meniscus (DMM) was carried out in adult C57BL/6 mice. Weight bearing asymmetry and hindpaw withdrawal threshold were measured up to 16 weeks post-surgery. Joint pathology was then assessed post-mortem at 16 weeks post-surgery. Another cohort of adult C57BL/6 mice underwent a modified surgical destabilization of the medial meniscus. Pain behaviour and joint pathology outcomes were measured 16 weeks and 20 weeks post-surgery. Osteoarthritis was induced in adult male Sprague Dawley rats via intra-articular injection of monosodium iodoacetate (MIA) or vehicle (50ul 0.9 % saline. A second cohort of male Sprague Dawley rats underwent either meniscal transection (MNX) or sham surgery. Rats then received intra-articular injections of either trkB-fc or human IgG. Pain behaviour was tested up to 3 hours post injection. Adult C57BL/6 mice underwent DMM or sham surgery. Pain behaviour was measured up to 16 weeks post-surgery. From 14 weeks post-surgery mice were orally dosed with either cordycepin or vehicle every two days for two weeks. Joint pathology was then assessed post-mortem at 16 weeks post-surgery. Results:There was a significant increase in weight bearing asymmetry from 13 weeks post DMM surgery in C57BL/6 mice, but no changes in hindpaw withdrawal thresholds. There were also significant increases in chondropathy and synovitis at 16 weeks post-surgery. When the surgical induction of the DMM model was modified there were still significant changes in joint pathology, but no significant changes in pain behaviour. Intra-articular injection of TrkB/fc chimera in rats with established MIA induced joint pain was found to acutely reduce weight bearing asymmetry and increase ipsilateral hindpaw withdrawal thresholds. There was also a significant reduction in pain behaviour in rats with MNX established joint pain when TrkB/fc chimera was injected into the knee joint. Following systemic administration of cordycepin in mice with DMM induced joint pain there was a significant reduction in weightbearing asymmetry when compared to vehicle treated mice. There was also a significant reduction in DMM induced chondropathy, subchondral bone thickening, and osteophytosis in mice treated with cordycepin compared to vehicle treated mice. Conclusions: The changes in pain behaviour outcomes between the traditional and modified DMM, despite similar joint pathology outcomes, suggests a role for meniscal damage as a peripheral driver of OA pain. Localised injection of TrkB/fc chimera into the knee joint of rats with both MIA and MNX induced joint pain was found to acutely reverse joint pain. This implies that peripheral BDNF may be involved in mediating OA joint pain. Oral administration of cordycepin was found to reduce both pain behaviour and joint pathology changes in the DMM model in mice. These results suggest a role for local protein translation underlying both OA chronic pain and joint damage.

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Nabar, Sean J. "Modern Techniques of Adjunctive Pain Control Lower Opioid Use, Pain Scores, and Length-of-Stay in Patients Undergoing Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis." Thesis, The University of Arizona, 2013. http://hdl.handle.net/10150/281776.

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A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.
Study Design. Retrospective analysis. Objective. To determine if the use of adjunctive pain medications (subcutaneous bupivacaine, dexmedetomidine infusion, and intravenous ketorolac) will reduce the need for opioids, reduce postoperative pain, and shorten length of hospital stay in patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion. Methods. Retrospective review of children 10 to 18 years with adolescent idiopathic scoliosis receiving posterior spinal fusion surgery over the past 10 years at Phoenix Children’s Hospital. Physicians managed the patients’ pain postoperatively with adjunctive medications in addition to intravenous and oral opioids. Variables of interest were local anesthetic bupivacaine delivered subcutaneously via elastomeric pain pump, sedative/analgesic dexmedetomidine infused for up to 24 hours postoperatively, and the NSAID ketorolac delivered intravenously. These three medications were used either alone or in some combination determined by the physician’s clinical judgment. Primary outcomes analyzed were normalized opioid requirement after surgery, VAS pain scores, and length of stay in the hospital. Results. One hundred and ninety-six children were analyzed with no significant differences in demographics. Univariate analysis showed that all three adjunct medications improved outcomes. A multivariate regression model of the outcomes with respect to the three medication variables of interest was developed to analyze the effects of the three medications simultaneously. The regression analysis showed that subcutaneous bupivacaine significantly reduced normalized opioid requirement by 0.98 mg/kg (P = 0.001) and reduced VAS pain scores by 0.67 points (P = 0.004). Dexmedetomidine significantly reduced the average VAS pain scores in the first 24 hours by 0.62 points (P = 0.005). Ketorolac had no effect in the multiple regression analysis. Conclusion. The use of subcutaneous bupivacaine provides good analgesia with low pain scores. A reduction in opioid requirement is beneficial and may be directly related to presence of the bupivacaine pump, although this may be limited by potential treatment bias. The three adjunct medications improve our outcomes favorably and should be studied prospectively.

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Strassels, Scott A. "The association of demographic and clinical characteristics with pain in persons who received hospice care in the United States /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/7953.

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Grimes, Jeffrey Scott. "The impact of a noise stressor on capsaicin-induced primary and secondary hyperalgesia." Thesis, Texas A&M University, 2003. http://hdl.handle.net/1969.1/249.

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In searching for new human pain models that more closely resemble clinical pain states, the capsaicin pain model has emerged as a viable model for both inflammatory and neuropathic pain states. A principal benefit of the capsaicin model is that it allows study of two different pain processes, primary and secondary hyperalgesia. Primary hyperalgesia is characterized by spontaneous pain and both heat and mechanical hyperalgesia. In addition, it is likely the result of activation and sensitization of both peripheral and central nociceptors. In contrast, secondary hyperalgesia is characterized by only mechanical hyperalgesia and is caused by the sensitization of central nociceptive neurons. Previous research utilizing the capsaicin pain model has primarily focused on the neural properties with little focus on the impact of affective states on capsaicin-related pain processes. The present study examined the impact of a noise stressor on both primary and secondary hyperalgesia. Results indicated that the effects of the noise stressor impacted secondary hyperalgesia, but not primary hyperalgesia.

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Dehghani, Mohsen. "Cognitive behavioural models of chronic pain and the role of selective attention." University of Sydney. Psychology, 2003. http://hdl.handle.net/2123/584.

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Cognitive-behavioural based models of chronic pain contend that appraisals of harm affect the individual�s response to pain. It has been suggested that fear of pain and/or anxiety sensitivity predispose individuals to chronicity. However, other factors such as pain self-efficacy are believed to mediate between experience of pain and disability. According to this view, pain is maintained through hypervigilance towards painful sensations and subsequent avoidance. Four studies were conducted in order to evaluate the structure of fear-avoidance models of chronic pain, and also, to examine the role of hypervigilance as an underlying mechanism in maintenance of pain. In study one, using a sample of 207 consecutive patients, two models were tested. First, fear of movement model as proposed by Vlaeyen et al. (1995a) was examined. It was found that negative affectivity has direct effects on the fear and avoidance of pain, which in turn, contributes to disability. In total, fear/avoidance accounted for a significant amount of the variance of disability. In addition, severity of pain was found to increase pain disability, while itself is influenced still by negative affectivity. These findings supported the model of fear of pain as described by Vlaeyen et al. (1995a). Further, we found that self-efficacy may mediate the impact of fear of pain on disability and reduces the perceived physical disability. At the same time, self-efficacy was shown to have direct reductive impact on disability. However, both studies indicated that people who are fearful in response to pain are more likely to develop disability, although self-efficacy may play a moderating role. In the studies one, two, and three, the role of hypervigilance in over attending to pain was investigated. In study one a large sample of 168 chronic pain patients were studied. Questionnaires measuring different aspects of pain and a computerised version of the Dot-Probe Task were administered. Four types of words related to different dimensions of pain and matched neutral words were used as stimuli. Reaction times in response to the stimuli were recorded. A factorial design 3x4x2x2 and ANOVAs were employed to analyse the data. Chronic pain patients showed a cognitive bias to sensory pain words relative to affective, disability, and threat-related words. However, contrary to expectations, those high in fear of pain responded more slowly to stimuli than those less fearful of pain. These results suggest that patients with chronic pain problems selectively attend to sensory aspects of pain. However, selective attention appears to depend upon the nature of pain stimuli. For those who are highly fearful of pain they may not only selectively attend to pain-related information but also have difficulty disengaging from those stimuli. In study two, 35 chronic pain patients were compared with the same number matched healthy subjects. Both groups completed measures of fear of pain, anxiety sensitivity, depression and anxiety, in addition to dot probe task. Results indicated that both groups show similar attentional bias to sensory words in comparison with other word types. However, the level of this biasness was higher for chronic pain patients. Lack of significant differences between patients and controls is discussed in the context of possible evolutionary value of sensitivity to pain as an adaptive reaction in healthy controls, and contrary, as a maladaptive response to pain in chronic pain patients. The results of the previous research suggest that chronic pain patients demonstrate cognitive biases towards pain-related information and that such biases predict patient functioning. The forth study examined the degree to which a successful cognitive-behavioural program was able to modify the observed attentional bias towards sensory pain words. Forty-two patients with chronic pain conditions for more than three months were recruited prior to commencing a cognitive-behavioural pain management program. Participants were assessed before the program, after the program and at one-month follow-up. Results confirmed that chronic pain patients exhibited biased attention towards sensory pain-related words at pre-treatment. These biases were still evident at post-treatment, but were no longer statistically significant at follow up. Multiple regression analyses indicated that the changes in attentional bias towards sensory words between post-treatment and follow-up were predicted by pre- to post- treatment changes in fear of movement (Tampa Scale for Kinesiophobia) but not other relevant variables, such as fear of pain or anxiety sensitivity. These results demonstrate that successful cognitive-behavioural treatments can reduce selective attention, thought to be indicative of hypervigilance towards pain. Moreover, these biases appear to be changed by reducing the fear associated with movement. Theoretically, these results provide support for the fear of (re)injury model of pain. Clinically, this study supports the contention that fear of (re)injury and movement is an appropriate target of pain management and that reducing these fears causes patients to attend less to pain-related stimuli.

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Erichsen, Helle Kirstein. "Characterisation of the spared nerve injury model of neuropathic pain /." Cph. : The Danish University of Pharmaceutical Scienes, Department of Pharmacology, NeuroSearch, Kongl. Carolinska Medico Chirurgiska Institutet, 2003. http://www.dfh.dk/phd/defences/Hellekirsteinerichsen.htm.

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Dableh, Liliane J. "Cannabinoid receptors in animal models of acute, tonic and chronic pain." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=29428.

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The aim of the work presented here is to evaluate the effects of cannabinoids in three animal models of pain: acute, tonic and chronic. The tail flick test (acute pain) was used to test the effect of the cannabinoid agonist, WIN 55,212--2, on tail withdrawal latency from a noxious radiant heat source. It was also tested on the allodynia induced by either endogenous release or exogenous administration of substance P. WIN 55,212--2 was antinociceptive in this test, and blocked the substance P-induced allodynia, suggesting a post-synaptic site of action. The formalin test (tonic pain) was used to test the effects of the endogenous cannabinoid agonist, anandamide and the cannabinoid receptor antagonist AM 281. Anandamide was antinociceptive (with a short duration of action), and AM 281 was pronociceptive. When administered concomitantly, AM 281 blocked the effects of anandamide. When given alone and in the absence of a noxious stimulus, AM 281 was without effect. (Abstract shortened by UMI.)

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28

Peleshok, Jennifer. "Skin innervation patterns and neurotrophic factor expression in neuropathic pain models." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106359.

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Neuropathic pain presents itself with many faces. It can be devastatingly painful leading to a person's inability to lead a productive life or it can be mild. In this thesis I discuss one of the countless possible mechanisms which could underlie the development and maintenance of this disorder; namely the involvement of peripheral changes in innervation. The approach taken in this thesis was mainly based on protein analyses, based on the assumption that protein expression (or lack thereof) is indicative of changes in the physiological properties of structures that either express or secrete proteins. I also address the models which are commonly used by researchers to elucidate the mechanisms underlying chronic neuropathic pain in hopes of developing viable treatments. The focus of this work is on the periphery, more specifically involving the glabrous skin of the rat hind paw. This skin is innervated by branches of the sciatic nerve which are comprised of, in part, sensory fibres. These are sub-classified into the thickly and thinly myelinated A-beta and A-delta afferents, respectively, as well as unmyelinated C-fibres. The latter population can be divided into two subgroups based on their peptide content where the peptide rich are termed peptidergic and the peptide-poor, non-peptidergic. This area also receives innervation from post-ganglionic sympathetic efferents. This thesis comprises three experimental chapters of my independent work into further exploring the models and mechanisms underlying the maintenance and generation of neuropathic pain. The first experimental chapter addresses the long term changes of skin innervation which occur following the application of a commonly used model of neuropathic pain, namely the chronic constriction injury (CCI) of the sciatic nerve model. I examined the myelinated afferent population as a whole, the unmyelinated peptidergic afferents as well as the non-peptidergic C-fibres from three days through 1.5 years following the application of the nerve injury. There was a persistent loss of myelinated afferents, loss and delayed sprouting of non-peptidergic C-fibres as well as a brief loss and permanent sprouting of peptidergic afferents within the upper dermis. The second study is a comparative examination of the morphological and behavioural changes following application of two very similar models of neuropathic pain. The CCI model is based on the application of loose chromic gut ligatures and the variation of this is the cuff model in which the chromic gut ligatures are replaced by a fixed diameter polyethylene cuff. The application of the cuff model resulted in a persistent mechanical hypersensitivity in contrast to the CCI in which the mechanical hypersensitivity resolved within about a month. However, the application of either model resulted in a transient thermal hypersensitivity. Innervation changes following application of the cuff model included a reduction in myelinated afferent density within the upper dermis in both models, the unmyelinated, non-peptidergic afferents declined in fibre density followed by a delayed recovery in the cuff model and the peptidergic afferents gradually declined and remained so following application of the cuff in contrast to the application of the CCI. The third chapter addresses the changes in the expression of nerve growth factor (NGF) and its receptors following CCI. The precursor form of NGF, proNGF was localized to mast cells, vascular endothelium and keratinocytes in the epidermis in naïve skin. Following injury, proNGF increased. After lesion, Schwann cells expressed high levels of the NGF receptor p75. The two receptors for NGF, TrkA and p75, were differentially regulated during the progression of the nerve injury. The work of this thesis has provided new findings documenting the morphological changes underlying the generation and maintenance of neuropathic pain as well as the molecular generators of these changes.
La douleur neuropathique peut se présenter sous plusieurs formes. Dans cette thèse, j'analyse les mécanismes périphériques pouvant déclencher et maintenir la douleur neuropathique. L'approche adoptée dans cette thèse est surtout basée sur une analyse de la concentration et distribution anatomique de protéines, avec l'idée sous-jacente que son niveau d'expression (ou absence d'expression) est révélatrice de changements physiologiques dans les structures qui produisent ou sécrètent ces protéines. Le focus de ce travail se déroule dans la périphérie, en particulier la peau non couverte de poils de la surface plantaire du membre postérieur du rat. Cette peau est innervée par des fibres nerveuses sensorielles provenant du nerf sciatique. Ces fibres sont normalement classées comme afférences myélinisées épaisses et finement myélinisées (A-bêta et A-delta respectivement), ainsi que comme fibres amyéliniques (C). La dernière population peut être divisée en deux sous-groupes en fonction de présence ou absence de neuropeptides en peptidergiques et non-peptidergiques. Cette région reçoit également une innervation par des fibres post-ganglionnaires sympathiques. Cette thèse est composée de trois chapitres expérimentaux. Le premier chapitre se penche sur les changements à long terme de l'innervation cutanée qui se produisent après l'application d'un modèle de douleur neuropathique couramment utilisé, à savoir la blessure par constriction chronique du nerf sciatique (CCI). J'ai examiné les changements des fibres myélinisées, des fibres amyéliniques peptidergiques, ainsi que des fibres non-peptidergiques dès trois jours après l'application de la lésion jusqu'à un an et demi après la lésion. Il y avait une perte persistante des afférences myélinisées, une perte suivie d'une récupération tardive des fibres C non-peptidergiques ainsi qu'une brève perte suivie de récupération permanente des afférences peptidergiques dans la partie supérieure du derme. Le second chapitre expérimental est un examen comparatif des changements morphologiques après l'application de deux modèles très similaires de douleur neuropathique. Le premier est la constriction chronique du nerf sciatique (CCI) suivant l'application de 4 ligatures; dans le deuxième la constriction du nerf sciatique est obtenue par l'application autour du nerf d'un segment de tube polyéthylène (cuff). L'application du « cuff » résultait en une hypersensibilité mécanique persistante, contrairement au CCI dans lequel l'hypersensibilité mécanique disparaissait dans un mois environ. Toutefois, les résultats de l'application des deux modèles sur la sensibilité thermique étaient similaires, avec une hyper-sensitivité à la chaleur qui durait environ un mois. Les afférences myélinisées étaient réduites en densité dans la partie supérieure du derme dans les deux modèles et cette baisse était permanente. Cependant, les afférences non-peptidergiques ont souffert une baisse de densité suivie d'un retour retardé à des valeurs des contrôles dans le modèle « cuff ». Dans ce dernier modèle, les afférences peptidergiques ont diminué progressivement en densité et n'ont pas récupéré, à la différence de l'application de la CCI. Le troisième chapitre expérimental concerne les changements dans l'expression du facteur de croissance nerveuse (NGF) et de ses récepteurs dans des animaux avec une lésion CCI. Le précurseur du NGF, proNGF a été localisé dans l'épiderme de la peau naïve. À la suite de la lésion CCI, nous avons détecté une augmentation du proNGF. Après la lésion, les cellules de Schwann avaient une expression très augmentée du récepteur du NGF p75. Les récepteurs au NGF, TrkA et p75 sont différentiellement régulés dans la période après la lésion du nerf. Le travail de cette thèse a eu comme objectif de clarifier les changements morphologiques contribuant au déclanchement et la manutention de la douleur neuropathique, ainsi que les mécanismes moléculaires de ces changements.

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29

Davies, Emily. "Development and evaluation of translational pain models using objective neurophysiological markers." Thesis, University of Bristol, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559475.

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Acute pain plays a fundamental role in survival, providing protection from potentially damaging stimuli. However, chronic pain is much less useful and is hugely detrimental to quality of life. An inadequately low number of chronic pain patients get meaningful analgesic treatment benefit, and very few novel analgesics have become available in recent years. This is due in part to a high failure rate of new analgesics in early clinical trials. with a significant number of these failures being due to lack of efficacy, thus questioning whether current animal models, and/or how pain is assessed in these models, sufficiently predict clinical efficacy. Development of translational pain models will bridge this gap between preclinical animal and human clinical research by providing experimental models that have similar underlying mechanisms. Additionally. use of translational objective measures of pain as pharmocodynamic endpoints will aid drug development. The work described in this thesis aimed to address these two critical issues, namely that animal and human pain models are often mechanistically different and are quantified using different outcome measures. The main focus of this project was translational inflammatory pain models with a central sensitisation component, a cardinal clinical feature or chronic pain. As secondary mechanical hyperalgesia results from central sensitisation. the work focused on development of models ill which secondary mechanical hyperalgesia is exhibited, combined with objective assessment of this mechanical hyperalgesia. The key findings of this project were two-fold. Firstly, a novel objective neurophysiological measure of mechanical pain was developed and validated in healthy human volunteers. Secondly, the occurrence of secondary mechanical hyperalgesia was investigated in an established translational inflammatory pain model in the rat (the ultraviolet-B (UV -13) model). and in a novel model which combines UV-B with heat rekindling to prolong central sensitisation. Finally. to bring the two aspects of the project together. the objective measure of mechanical pain in humans was used to investigate secondary mechanical hyperalgesia in a translational experimental inflammatory pain model in healthy human volunteers. The development of translational experimental models of inflammatory pain. with emphasis on the clinically relevant phenomenon of central sensitisation, will improve transition of novel analgesics into the clinic. The objective measure of mechanical pain in humans described here is a neurophysiological technique that will aid future pain research when used alongside subjective measures of pain, creating a multidimensional approach to pain assessment. It also has the potential to be back-translated to the laboratory rat for future quantification of secondary mechanical hyperalgesia and central sensitisation ill translational models such as the UV-B model.

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Rode, Frederik. "Pharmacological testing in the spared nerve injury model of neuropathic pain /." Cph. : The Danish University of Pharmaceutical Sciences, Department of Pharmacology, 2005. http://www.dfuni.dk/index.php/Frederik_Rode/1938/0/.

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31

Gomes, KÃtia do Nascimento. "Modelo experimental de disfunÃÃo temporomandibular em ratos." Universidade Federal do CearÃ, 2005. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=287.

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Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
Estudos de comportamentos espontÃneos, atividade farmacolÃgica sobre os comportamentos alterados, avaliaÃÃo histopatolÃgica e alteraÃÃo de peso corporal foram realizados em ratos (180-300g), atravÃs da administraÃÃo de Adjuvante completo de Freund (CFA) na regiÃo da articulaÃÃo temporomandibular de ratos, a fim de investigar se um estÃmulo inflamatÃrio crÃnico promove alteraÃÃo de comportamento espontÃneo comparado a estÃmulo agudo ou subagudo como a formalina 2,5%. Os animais apÃs a injeÃÃo de CFA, formalina 2,5% e soluÃÃo salina fisiolÃgica 0,9% foram observados diariamente durante 30 minutos por 7 dias onde foram sacrificados para a remoÃÃo da regiÃo articular e periarticular para avaliaÃÃo de alteraÃÃo de parÃmetros inflamatÃrios frente a um estÃmulo pelo CFA e pela formalina 2,5% comparando com o grupo controle. As principais alteraÃÃes promovidas pelo CFA ocorreram no tempo de execuÃÃo de alguns comportamentos como movimento de rotaÃÃo da mandÃbula ou mastigaÃÃo (chewing like), tempo de descanso e sono (rest/sleeping), aparente congelamento (freezing) e auto cuidado como coÃar a face se pata anterior (grooming ou rubbing), enquanto que no grupo de animais da formalina 2,5%, os comportamentos alterados formam grooming e scratching. Os estudos comportamentais demonstram que o CFA possui uma atividade tempo dependente sobre comportamentos, pois essas alteraÃÃes ocorreram a partir do 2Âdia e persistiu atÃ o 7Âdia apÃs a administraÃÃo do CFA, ao passo que a formalina apresentou uma atividade principal no 1Â dia de injeÃÃo. A administraÃÃo de drogas analgÃsicas (Morfina 4mg/Kg; Indometacina, 5mg/Kg e LidocaÃna com fenilefrina) demonstrou que o comportamento chewing like foi sensÃvel Ã aÃÃo da morfina e indometacina, o sleeping foi aumentado por administraÃÃo de lidocaÃna e indometacina, o tempo de execuÃÃo do comportamento grooming foi reduzido por atividade da morfina e lidocaÃna e o comportamento freezing nÃo foi alterado por aÃÃo de nenhuma das drogas administradas. Comparativamente, os comportamentos alterados pela atividade nociceptiva da formalina 2,5% na regiÃo orofacial dos animais foram grooming e scratching. A morfina e a lidocaÃna foram efetivas em reduzir o grooming e o scratching desenvolvidos pela formalina. A atividade de drogas classicamente analgÃsicas testadas sobre esses comportamentos pode caracterizÃ-los como nociceptivos. Foi observado tambÃm que o peso corporal dos animais nÃo foi alterado pela induÃÃo inflamatÃria do CFA. Comparando sessÃes histolÃgicas da regiÃo articular e periarticular da ATM dos ratos, observamos que no grupo do CFA hÃ presenÃa de infiltrado inflamatÃrio linfocitÃrio intenso comparado ao grupo da formalina, alÃm de alteraÃÃes degenerativas e pequeno infiltrado inflamatÃrio periarticular. NÃs sugerimos que o fenÃmeno da neuroplasticidade estÃ relacionado Ãs alteraÃÃes comportamentais desenvolvidas pelo CFA e a identificaÃÃo de comportamentos relacionados a sua atividade inflamatÃria pode fornecer subsÃdios para a avaliaÃÃo de novos e melhores agentes terapÃuticos para o tratamento da dor orofacial como tambÃm avaliaÃÃo dos benefÃcios dos tratamentos jÃ existentes, em consonÃncia com os avanÃos no estudo de dor experimental.
Studies on rats spontaneous behaviors and pharmacological effects of drugs on them, as well as their body weight and histopathological analysis of their joints were carried out to investigate the effect of chronic inflammation of the temporomandibular articulation induced by the administration of Complete Freund Adjuvant (CFA) compared with the acute and subacute stimulus of 2.5% formalin. After CFA, 2.5% formalin and 0.9% saline injection, the animals were daily observed during 30 minutes for 7 days; thereafter, they were killed for removal of the articular and periarticular region for evaluation of inflammatory changes induced by CFA and formalin compared with control rats. The main behavioral changes induced by CFA concerned chewing-like, rest/sleeping, freezing, grooming or rubbing whereas those induced by formalin were grooming and scratching. The CFA-induced behavioral changes were time-dependent from the 2nd up to the 7th day, while the formalin-induced changes occurred in the 1st day only. For pharmacological testing, morphine (4 mg/kg), indomethacin (5 mg/kg) and lidocaine with phenilephrine were used. In the CFA rats, morphine reduced significantly chewing-like and grooming, indomethacin decreased grooming and increased sleeping. Freezing was not changed by any drugs. In the formalin rats, grooming and scratching towards the orofacial region were increased and those behaviors were significantly decreased by morphine and formalin. The effects of the drugs on the different behaviors shown above show their nociceptive meaning. Moreover, the body weight of the animals was not changed. In both CFA and formalin groups, the histological analysis evidenced degenerative and small periarticular inflammatory infiltration. Neuroplasticity changes may be related to the CFA induction and the nociceptive meaning of the behaviors may be useful for experimental therapeutic studies.

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Farmer, Melissa. "Mouse models of urogenital pain: causes and consequences of infection and inflammation." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=104576.

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The goal of this thesis was to examine the utility of animal models of urogenital pain to explore the causes and consequences of acute and chronic genital and non-genital pain. In the first review chapter entitled "Animal Models of Dyspareunia," the validity and reliability of animal models associated with dyspareunia (painful intercourse) is examined in terms of how closely they parallel the clinical presentation of their respective pain conditions. The review reveals that many of these models are limited by the lack of specificity of their pain behaviours and/or poor correlations between pain and tissue pathology. The second chapter entitled "Repeated Vulvovaginal Fungal Infections Cause Persistent Pain in a Mouse Model of Vulvodynia," describes a mouse model of provoked vestibulodynia developed and used to examine the hypothesis that persistent vulvar pain may result from prolonged vulvovaginal inflammation due to Candida albicans infection. We found that a subset of mice exhibited vulvar mechanical hypersensitivity following three fully resolved Candida infections, as well as following a single, extended infection and repeated vulvar injections of the inflammatory compound zymosan. Following repeated Candida infections, allodynic mice showed significant increases in vulvar innervation, including peptidergic afferent and sympathetic efferent nerve fibers. This model provides evidence for biological mechanisms underlying chronic vulvar pain and sheds doubt on previous assumptions that vulvar pain is merely a consequence of impaired sexual response. In the final empirical investigation, the hypothesis that sexual motivation can be directly modulated by genital versus non-genital pain was evaluated. Whereas genital and non-genital tonic inflammatory pain did not impact the sexual behaviour of male mice, both types of pain resulted in reduced female sexual motivation and behaviour. Together, this body of work demonstrates the potential utility of novel animal models of urogenital pain to study the etiology and impact of pelvic pain in humans.
L'objectif de cette thèse était par conséquent d'examiner l'utilité des modèles animaux de douleur urogénitale afin d'explorer les causes et les conséquences de la douleur aiguë et chronique au niveau des organes génitaux et non-génitaux. Le premier chapitre intitulé "Des modèles animaux de la dyspareunie," examine la validité et la fiabilité des modèles animaux de la dyspareunie en ce qui concerne le degré de parallèle de la présentation clinique avec leurs conditions de douleur respectives. La revue de littérature démontre que plusieurs de ces modèles sont limités par le manque de spécificité des comportements de douleur et/ou par de faibles corrélations entre la douleur et la pathologie des tissus. Le deuxième chapitre intitulé "Les infections fongiques repetées de la partie vulvo-vaginale causent une douleur persistante dans un modèle murin de la vulvodynie," décrit un modèle murin de vestibulodynie provoquée développé et utilisé dans le but d'examiner l'hypothèse que la douleur vulvaire persistante peut résulter d'une inflammation prolongée vulvo-vaginale secondaire à une infection à Candida albicans. Nous avons constaté qu'un sous-ensemble de souris a démontré une hypersensibilité mécanique au niveau de la vulve après trois résolutions complètes d'infections à Candida ainsi qu'après une seule infection prolongée incluant des injections vulvaires répétées de zymosan, soit un composé inflammatoire. Suite à des infections répétées à Candida, les souris présentant une allodynie vulvaire démontraient une augmentation significative de l'innervation de la vulve ainsi que des fibres afférentes peptidergiques et des fibres nerveuses efférentes sympathiques. Ce modèle fournit des preuves pour les mécanismes biologiques causantes des douleurs vulvaires chroniques prouvant les hypothèses précédentes que la douleur vulvaire est simplement une conséquence de la reponse sexuelle réduite. La dernière étude empirique, intitulé "Pas ce soir chéri, j'ai un mal de tête: Les différences entre les sexes dans l'effet de la douleur sur la motivation sexuelle," a évalué l'hypothèse que la présence de douleur génitale contrairement à la douleur non-génitale peut directement influencée la motivation sexuelle. Bien que la douleur inflammatoire tonique au niveau de la région génitale et des régions non génitales n'aient pas eu d'impact sur le comportement sexuel des souris mâles, les deux types de douleur ont entraîné une réduction significative de la motivation sexuelle ainsi que des comportements sexuels chez la souris femelle. L'ensemble de ces travaux démontrent l'utilité potentielle de nouveaux modèles animaux de douleur urogénitale pour étudier l'étiologie et l'impact de la douleur pelvienne chez l'humain.

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Laycock, Helen Catherine. "Sensory, cytokine and metabolic profiling of human experimental burn injury pain models." Thesis, Imperial College London, 2017. http://hdl.handle.net/10044/1/61633.

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Burn injury-associated pain represents a considerable burden to patients and is inadequately managed in the clinical setting. It is thought to be a consequence of the “burn-injury inflammatory soup” produced in the wound that activates and sensitises peripheral nociceptors. However the composition of this fluid and its interaction with peripheral nociceptors in incompletely defined, limiting the application of a mechanistic-based approach to burn injury-associated pain management. Two human experimental burn injury pain models (thermal injury and UVB injury) represent a potential opportunity to further elucidate these complex peripheral processes. Nonetheless controversy exists regarding their respective somatosensory phenotypes and the associated peripheral inflammatory protein and metabolic profiles remain uncharacterised. This thesis aimed to elucidate a more comprehensive understanding of the somatosensory changes and components of the “burn-injury inflammatory soup” with respect to inflammatory proteins and the metabolome. Forty-five healthy subjects had an experimental pain model imparted on their forearm (thermal injury, capsaicin injury or UVB injury models). Somatosensory testing and dermal microdialysis were performed. A multiplex microbead assay array was used to analyse dermal microdialysates to compare temporal within and between injury model inflammatory protein concentrations. Untargeted ultra performance liquid chromatography-mass spectrometry was used for global profiling of dermal microdialysates with the aim of determining significant compounds that separated injury models. Although some similarities were apparent in the three injury models with respect to secondary somatosensory changes and concentrations of the inflammatory proteins IL6, IL8 and CCL2, overall the three experimental pain models displayed distinct somatosensory, inflammatory protein and metabolic profiles. The UVB injury model appears to represent a less acute inflammatory reaction than is seen in the thermal injury model. Together these results support the use of the thermal injury experimental pain model to further investigate peripheral processes involved in acute burn injury-associated pain.

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Patel, S. "Neuronal mechanisms in rodent models of osteoarthritic and cancer-induced bone pain." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1348543/.

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Whilst pain serves a physiological function, chronic diseases such as osteoarthritis and cancer of the bone involve central neurones and peripheral nociceptors becoming sensitised to heighten or extend the pain experience temporally, which is detrimental to the quality of life. Mechanisms underlying central sensitization of neurones are examined in this thesis in two rodent models of pain: osteoarthritis (OA) and cancer-induced bone pain (CIBP) using pharmacology, mapping of receptive field size for lamina I neurones in OA animals and TENS. Pharmacological studies focused on NMDA and P2X3 and P2X2/3 receptors using ketamine, ifenprodil and a novel agent: AF-353. Ketamine reduced the neuronal responses to noxious stimuli in OA animals to levels observed in naïve animals. However effects were significantly stronger in CIBP animals where doses 10-fold lower produced the same effect suggesting post-synaptic NMDA receptors have a significant role in the maintenance of CIBP. Ifenprodil, which acts at NR2B subunit containing receptors, which are presynaptically located and may thus control release of neurotransmitters from the afferent terminal, more strongly inhibited electrical stimuli evoked responses in OA animals. Inhibition of natural stimuli evoked neuronal responses were similar in both models suggesting the importance of primary afferent drive in maintenance of central sensitization in OA and CIBP. AF-353 which inhibits the actions of ATP on pre-synaptically located P2X3 and P2X2/3 receptors was found to profoundly inhibit neuronal responses to noxious thermal stimuli in CIBP suggesting that thermal-stimuli induced hyperalgesia has a central component driven by the purinergic system. Finally, TENS a nonpharmacological intervention was found to have no significant effect on evoked responses of lamina V neurones in CIBP animals questioning its suitability in managing chronic pain. Differing pharmacology appears to contribute to the maintenance of central sensitization in OA and CIBP suggesting that more targeted therapy may be more clinically appropriate.

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Boorman, Damien. "Developing Preclinical Models of Conditioned Placebo Analgesia in Rats with Neuropathic Pain." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29581.

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Chronic pain remains an insidious, debilitating and intractable condition. Its worldwide prevalence is estimated to be up to 27.5%, with the majority of these people undertreated, largely due to the failures of pharmacotherapies. Placebo analgesia – the phenomenon of experiencing pain relief from pharmacologically inert treatments – has enormous therapeutic potential to help ease the suffering of chronic pain patients, and thus ease the economic, social and psychological burden of this condition. Human neuroimaging studies have identified many brain regions involved in the generation of placebo analgesia, but only animal models can investigate its neurobiological mechanisms at cellular and subcellular levels. To date, only a handful of these models have been developed, and only 5 prior studies have attempted to do so in the context of chronic pain. Therefore, the overarching aim of this thesis was to develop new preclinical models of placebo analgesia in rats with chronic pain and investigate the neural mechanisms that underpin this response. Chapter 2 presents the first of these models, which used pharmacological conditioning techniques to successfully elicit placebo analgesia from 36% of male rats and 25% of females. Furthermore, along with Chapter 3, I began investigation into the cellular mechanisms of placebo analgesia by comparing the neuronal and glial activity between rats that demonstrated placebo and those that did not. Chapter 4 documents my attempt to improve the model presented in Chapter 2. In Chapter 5, I take a different experimental approach and use response-conditioning techniques to elicit both placebo analgesia and nocebo hyperalgesia in nerve-injured rats. Finally, in Chapter 6, I propose a new theoretical model of the essential neural circuitry that underlies opioid-conditioned placebo analgesia. I conclude by outlining how these new preclinical models of placebo analgesia can be used to interrogate this circuity and assist in the development of new treatments for chronic pain that harness or exploit the neural mechanisms of placebo analgesia.

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Neddenriep, Bradley. "The Analgesic-Like Properties of Alcohol in Animal Models of Chronic Pain." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5923.

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Chronic pain and excessive alcohol consumption are individually problems in our society today. Alcohol Use Disorder (AUD) affects 15.1 million adult Americans each year. Chronic pain affects over 100 million people annually in the United States. However, there is growing evidence suggesting that these two conditions can often be interrelated with chronic pain increasing consumption of alcohol, and excessive alcohol consumption increasing pain that leaves a feedback cycle trapping millions of patients in an ever worsening spiral. Large population-based studies show an association between pain and alcohol abuse, suggesting a link between increased alcohol use and reduced pain. While rodent studies consistently demonstrate antinociception following acute ethanol administration in hot-plate and tail-flick tests. However, little is currently known about the effects of alcohol in chronic pain models. We hypothesize that acute ethanol administration will possess analgesic-like properties in models of chronic pain by engaging opioid receptors in addition to its more commonly studied action at the GABA receptor. The first aim of this study was to characterize the antinociceptive effects of alcohol in Complete Freund’s Adjuvant (CFA) and Chronic Constriction Injury (CCI) mouse models of chronic inflammatory and neuropathic pain models, respectively. The second aim of this study is to investigate the mechanisms behind ethanol's analgesic like effects including tolerance, receptor activation and correlates with blood alcohol content. Lastly, we investigated whether alcohol maintains its analgesic-like effects in non-reflexive assays in addition to effects in reflexive assays.

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DONVITO, GIULIA. "PHARMACOLOGICAL EFFECTS OF PALMITOYLETHANOLAMIDE (PEA) IN DIFFERENT ANIMAL MODELS OF NEUROPATHIC PAIN." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2016. http://hdl.handle.net/10281/101790.

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Neuropathic pain is defined by the International Association for the Study of Pain (IASP) as pain that arises as a direct consequence of a lesion or disease affecting the somatosensory system. Neuropathic pain is often poorly alleviated by first-, and second-line medications recommended by IASP due to lack of efficacy and/or dose-limiting side-effects. Hence, there is an urgent need to develop novel mechanism-based therapeutic agents that are highly efficacious and well tolerated to improve relief of neuropathic pain. Palmitoylethanolamide (PEA) is the parent molecule of ALIAmides (Autacoid Local Injury Antagonism Amides), a group of endogenous fatty acid derivatives sharing anti-inflammatory and antinociceptive effects with the endocannabinoid family mainly through the down-modulation of local mast cell degranulation. Several evidences in literature show the antinociceptive effect of PEA in different animal models of pain, such as spinal cord injury, chronic constriction injury of the sciatic nerve, carrageenan-induced acute inflammation, and complete Freund’s adjuvant-induced chronic inflammation. Based on these fundings, the aim of this study is to further explore the therapeutic potentiality of PEA in resolving painful states in three very common forms of neuropathic pain in human associated to osteoarthritis, diabetes, and chemotherapy. Osteoarthritis (OA) is the most common chronic joint disease characterized by a progressive destruction of cartilage, resulting in pain, and loss of articular function. The monosodium iodoacetate (MIA) rat model of OA was used to investigate the effects of PEA. Under a chronic treatment regiment, PEA was able to completely abolish knee swelling and thermal hyperalgesia, as index of inflammation. Moreover, treatment with PEA resulted in a significant relief of mechanical allodynia, as index of neuropathic pain. Futhermore, PEA treatment completely restored locomotor functionality, and is also able to preserve cartilage from damage. Diabetes mellitus is a metabolic syndrome today affecting 382 million people. One of the most disabling long-term complications of diabetes is diabetic neuropathy. The well established streptozotocin (STZ)-induced mice model of type 1 diabetes was emploied to explore the antinociceptive effect of PEA in diabetic neurophaty. PEA relieved mechanical allodynia, counteracted nerve growth factor deficit, improved insulin level, preserved Langherans islet morphology reducing the development of insulitis in diabetic mice. Chemotherapy-induced neuropathic pain (CINP) is another common form of neurophatic pain, affecting up to 90% of patients. The effect of PEA in paclitaxel model of CINP, one of the most common used antineoplastic drugs in clinic, was investigated. Preliminary results show that PEA is able to evoke a total antiallodynic effect in CINP model, after acute administration. The results of this thesis show the pharmacological effect of PEA to relieve neuropathic pain associated to osteoarthritis, diabetes, and chemotherapy, three very common diseases in human, that lack a resolutive, and effective treatment. These findings allow us to suggest a therapeutic use of PEA in clinic.

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COMI, ELEONORA. "Chronic pain evaluation in animal models of osteoarthritis: behavioural and pharmacological considerations." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2017. http://hdl.handle.net/10281/158318.

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L'osteoartrite (OA) è una patologia degenerativa cronica molto comune negli anziani. Il dolore rappresenta il sintomo di OA più invalidante e precoce per il paziente. Ad oggi non esistono terapie curative per questa patologia. Inoltre, i farmaci più comunemente usati per contrastare il dolore OA sono spesso associati ad effetti collaterali. CR4056, ligando dei recettori imidazolinici-2, è un nuovo farmaco analgesico dimostratosi efficace in diversi modelli animali di dolore. Gli scopi di questo progetto sono stati analizzare la progressione del dolore OA e valutare l'efficacia di CR4056, comparato ad un FANS standard (naproxene), in due modelli di OA in ratto, in grado di replicare le componenti dolorose e strutturali della patologia umana. L’OA è stata indotta mediante singola iniezione intra-articolare di 1 mg/50 μl di monosodio iodoacetato (MIA) o mediante rottura del menisco mediale (MMT) nel ginocchio destro di ratti maschi. L’iniezione di MIA causa la degenerazione della cartilagine, mediante inibizione locale della glicolisi, mentre la resezione del legamento collaterale mediale e del menisco mediale destabilizza l’articolazione, inducendo degradazione della cartilagine e alterazioni dell’osso subcondrale. Nei modelli MIA e MMT la soglia algogena meccanica è stata valutata come allodinia e rispettivamente iperalgesia primaria o secondaria. Sono stati poi determinati l’asimmetria statica o dinamica del peso supportato delle zampe posteriori ipsilaterale e contralaterale (HPWD), la funzionalità motoria e l’attività locomotoria. L’espressione di proteine correlate al dolore (GFAP, pp38, pERKs e Iba-1) è stata valutata nel midollo spinale lombare ipsilaterale e contralaterale o nei DRG L4 e L5 ipsilaterali. CR4056 (2, 6 e 20 mg/kg) e naproxene (10 mg/kg) sono stati somministrati come trattamenti acuti e subacuti in entrambi i modelli. L’iniezione di MIA ha indotto uno sviluppo significativo di iperalgesia meccanica primaria, allodinia meccanica e asimmetria statica e dinamica di HPWD; nessun cambiamento si è verificato nell’attività locomotoria. CR4056 (6 e 20 mg/kg) ha ridotto significativamente l’allodinia e l’iperalgesia, dopo trattamento acuto (7 e 14 giorni post MIA) e soprattutto subacuto (da 14 a 21 giorni post MIA), mentre il naproxene è stato efficace solo dopo trattamento subacuto. Entrambi i composti sono risultati privi di effetto sull’asimmetria statica e dinamica di HPWD. L’espressione di pp38 e pERKs nel midollo spinale lombare ipsilaterale non si è dimostrata differente tra sham e MIA. L’iniezione di MIA ha invece indotto un aumento significativo delle cellule microgliali attivate (Iba1+) nella corna dorsale ipsilaterale del midollo spinale L4. Il trattamento subacuto con entrambi i composti ha ridotto significativamente tale attivazione della microglia. L’operazione MMT ha indotto uno sviluppo significativo di una progressiva asimmetria statica di HPWD e di una stabile iperalgesia meccanica secondaria. Non sono stati invece evidenziati allodinia, asimmetria dinamica di HPWD e cambiamenti nell’attività locomotoria e funzionalità motoria. CR4056 (20 mg/kg) e naproxene hanno dimostrato un significativo effetto anti-iperalgesico solo dopo trattamento acuto (28 giorni post MMT). Invece, il trattamento subacuto (da 28 a 42 giorni post MMT) con CR4056 (6 mg/kg) ha ridotto significativamente l’asimmetria statica di HPWD, mentre il naproxene è risultato privo di effetti. Non si sono verificate variazioni nell’espressione di GFAP e Iba-1, rispettivamente nei DRG L4 e L5 ipsilaterali e nella corna dorsale ipsilaterale del midollo spinale L4, tra sham e MMT. Entrambi i modelli MIA e MMT sono caratterizzati da una componente di dolore OA comparabile a quella umana, con tuttavia un differente contributo dei meccanismi dolorosi periferici e centrali. Inoltre, i dati ottenuti dimostrano che CR4056 potrebbe costituire un nuovo efficace trattamento per il dolore OA.
Aim: Osteoarthritis (OA) is a disabling and painful condition very common in the elderly. Pain is the earliest symptom of OA. To date there are still no curative drugs for this condition. Moreover, the chronic use of first-line pharmacological treatments to handle OA pain is frequently associated with side effects. CR4056, an imidazoline-2 receptor ligand, is a promising analgesic drug that has been reported to be effective in several animal models of pain. The aims of my project were to analyze and compare the time-related progression of OA pain and to evaluate the efficacy of CR4056, in comparison with a standard NSAID (naproxen), in two well-established rat models of OA, able to mimic the painful and structural components of the human pathology. Methods: Knee OA was induced either by single intra-articular injection of 1 mg/50 μl monosodium iodoacetate (MIA) or by medial meniscal tear (MMT) in the right knee of male rats. The local injection of MIA produces cartilage degeneration, through the local inhibition of glycolisis, while the transection of both the medial collateral ligament and the medial meniscus leads to joint destabilization, resulting in cartilage degeneration and subchondral bone alterations. The withdrawal threshold to mechanical stimulation was assessed both as allodynia and either as primary or secondary hyperalgesia, in MIA and MMT model, respectively. Pain behaviour was further evaluated as static and dynamic hind paw weight bearing (HPWD) asymmetry between the ipsilateral and the contralateral limb, and as changes in motor function and/or locomotor activity. Pain-related proteins (GFAP, pp38, pERKs and Iba-1) expression was assessed in either ipsilateral and contralateral lumbar spinal cord or ipsilateral L4 and L5 dorsal root ganglions (DRGs), in either MIA or MMT model. CR4056 (2, 6 and 20 mg/kg) and 10 mg/kg naproxen were administered as acute and sub-acute treatments in both models. Results: MIA model was characterized by the significant development of primary mechanical hyperalgesia, mechanical allodynia and asymmetry in both static and dynamic HPWD. No changes were detected in locomotor activity after MIA injection. 6 and 20 mg/kg CR4056 significantly and dose-dependently reduced both allodynia and hyperalgesia, after acute (7 and 14 days after MIA) and especially after repeated treatment (from 14 to 21 days post-MIA), whereas naproxen was effective after sub-acute treatment only. Both compounds had no significant effect on static and dynamic HPWD changes. No difference was detected in pp38 and pERKs expression in ipsilateral lumbar spinal cord, between MIA and sham group. On the other hand, a significant increase in the number of Iba-1 positive, morphologically identified, activated microglia in ipsilateral L4 spinal cord dorsal horn occurred, 21 days after MIA injection. Sub-acute treatment with 6 mg/kg CR4056 and naproxen reversed MIA-induced microglia activation. MMT surgery induced the significant development of a progressive asymmetry in static HPWD and a long-lasting secondary mechanical hyperalgesia. No mechanical allodynia nor changes in dynamic HPWD, motor function and locomotor activity were detected after MMT surgery. 20 mg/kg CR4056 and naproxen promoted a mild but significant anti-hyperalgesic effect, after acute treatment (28 days post-surgery) only. Conversely, repeated treatment (from 28 to 42 days post-surgery) with 6 mg/kg CR4056 significantly reduced the progression of static HPWD asymmetry, whereas naproxen had no effects. No difference in GFAP or Iba-1 expression were detected, in either ipsilateral L4 and L5 DRGs or ipsilateral L4 spinal cord dorsal horn, between MMT and sham group. Conclusions: Both MIA and MMT OA models display a pain behaviour comparable to human OA, with however different relative contribution of peripheral and central pain mechanisms. Moreover, the data obtained showed that CR4056 may represent a new effective treatment option for OA pain.

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Gorgon, Edward James. "Improving back pain care in the hospital setting." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29414.

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Redesigning how care is structured and delivered has been identified as a potential solution to enable implementation of best practice care for back pain. Redesigning care requires a deep understanding of local needs and context, and participation of stakeholders in the process to promote relevance, acceptance, and uptake. This thesis includes studies that have contributed toward defining the problem, identifying potential solutions, and proposing a new service to improve care for people with chronic back pain. The aim of the thesis was to complete the design phase of a new service for chronic back pain in a hospital setting. This thesis used different methods of research to conduct needs assessment and service design guided by an intervention mapping approach. Needs assessment was conducted through quantitative and qualitative evaluations of current care (Chapter 2 and Chapter 3). Service design was undertaken by creating a logic model of the health problem and a logic model of change, and identifying key components of a new service using information from the needs assessment and stakeholder feedback (Chapter 4, Chapter 5, and Chapter 6). As part of service design, a feasibility study protocol was designed to test key components of a new service for chronic back pain (Chapter 7). The needs assessment studies demonstrated that current service delivery is largely not structured to provide patients with timely and coordinated, long-term management. Whilst the clinical record review showed that existing practice involved good uptake of guideline recommendations, the focus groups and interviews suggested that many patients might be disengaging due to misaligned care expectations and a pathoanatomical focus. The service design process with stakeholder participation showed overall agreement with the needs assessment findings and proposed key components of a new service. This participatory process also revealed potential barriers related to clinician sensitivities and challenges with reimagining traditional roles which could adversely impact progress in the next steps of the service development process. This thesis has contributed to achieving the aim of completing the design phase of a new service for chronic back pain in a hospital setting. Moreover, this thesis provided new insights into the structures and processes that would need to be created to enable and support best practice care for chronic back pain.

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Bura, S. Andreea. "New animals models to evaluate therapeutic targets for pain, cognitive and eating disorders." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/31821.

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Animal models are crucial to improve the knowledge of the mechanisms underlying the different pathological processes. These models are also excellent tools to facilitate the research of new targets for the treatment of different diseases and to evaluate the benefit/risk ratio of the potential new treatments. We have focussed this research work in the study of a new potential targets for pain, cognitive and eating disorders using new animal models developed in our laboratory. We first investigated the effects of the interaction between cannabinoids and nicotine on cognitive processes and metabolism using different behavioural models and new experimental devices. In a second part of this work, we investigated new therapeutic targets for neuropathic pain and for this purpose we developed a new behavioural model to improve the study of the therapeutic potential and possible side-effects of novel compounds.
Los modelos animales son cruciales para mejorar el conocimiento sobre los mecanismos que constituyen la base de los diversos procesos patológicos. Estos modelos representan también excelentes herramientas para facilitar la investigación de nuevas dianas para el tratamiento de estas enfermedades y para evaluar el cociente beneficio/riesgo de los nuevos tratamientos potenciales. Este trabajo de investigación se encuentra centrado en el estudio de nuevos dianas terapéuticas para el dolor, los procesos cognitivos y los desórdenes alimentarios utilizando nuevos modelos animales desarrollados en nuestro laboratorio. En primer lugar, hemos investigado los efectos de la interacción entre los cannabinoinoides y la nicotina a nivel los procesos cognitivos y del metabolismo usando diversos modelos comportamentales y nuevos dispositivos experimentales. En una segunda parte de este trabajo, hemos estudiado nuevas dianas terapéuticas para el dolor neuropático y hemos desarrollado para este propósito un nuevo modelo comportamental que permite evaluar el potencial terapéutico y los posibles efectos secundarios de nuevos compuestos.

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Fisher, Kim Noël. "The contribution of metabotropic glutamate receptors to models of persistent and chronic pain." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0022/NQ50160.pdf.

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Fisher, Kim Nüel. "The contribution of metabotropic glutamate receptors to models of persistent and chronic pain /." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=35699.

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The possible involvement of spinal metabotropic glutamate receptors (mGluRs) were examined in animal models of persistent and chronic pain. In Study 1, it was shown that spinal administration of relatively selective group I mGluR antagonists, or a selective group III mGluR agonist, but not a non-selective mGluR antagonist, slightly, but significantly reduced nociceptive scores in the rat formalin test Also, spinal administration of a non-selective mGluR agonist, or a selective group I mGluR agonist, but not a relatively selective group II agonist, enhanced formalin-induced nociception. The pro-nociceptive effects of these agents were reversed by a non-selective mGluR antagonist or by an N-methyl-D-aspartate receptor (NMDAR) antagonist. In Study 2, it was shown that intrathecal administration of two non-selective mGluR agonists or a selective group I mGluR agonist, but not a selective group II or group III mGluR agonist, produced spontaneous nociceptive behaviours, (SNBs) in rats. Also, the SNBs induced by these agents were reduced by a non-selective mGluR antagonist or by an NMDAR antagonist. In Study 3, it was shown that intrathecal administration of a selective group I mGluR agonist produced persistent mechanical allodynia, mechanical hyperalgesia and heat hyperalgesia in rats. In Study 4, it was shown that early, but not late intrathecal administration of a relatively selective group I mGluR antagonist reduced nociceptive behaviours, in a model of neuropathic pain. In Study 5, it was shown that intrathecal administration of a selective group I mGluR antagonist reduced mechanical allodynia and cold hyperalgesia, while a selective group II mGluR agonist and a selective group III mGluR agonist only reduced mechanical allodynia and cold hyperalgesia, respectively, in the neuropathic pain model. Results from these studies first suggest that spinal group I mGluRs may be more critically involved in the development of chronic nociceptive behaviours, compared to persis

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Ambrosini, Snijezana Sue Snez. "Intracellular messengers involved in nociceptive behaviours induced by intrathecal (R,S)-3,5-dihydroxyphenylglycine." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80165.

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We investigated the role of two intracellular second messengers, extracellular signal-regulated protein kinase (ERK), and protein kinase C (PKC) in a model of persistent pain, using intrathecal (i.t) (R,S )-DHPG to induce spontaneous nociceptive behaviours (SNBs). SNBs were measured in animals that were treated with an ERK inhibitor (PD 98059), and a PKC inhibitor (GF 109203X) compared with controls. Mechanical allodynia, was measured using paw withdrawal thresholds in the von Frey test, and thermal hyperalgesia was measured using response latencies in the plantar test. In study 1, it was shown that spinal administration of PD 98059, dose-dependently decreased SNBs, and reduced mechanical allodynia and thermal hyperalgesia. In study 2, it was shown that i.t. pretreatment with the GF 109203X, reduced SNBs and thermal hyperalgesia, but not mechanical allodynia. These results suggest that both ERK and PKC are involved in SNBs and the concomitant and thermal hyperalgesia and possibly mechanical allodynia.

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De, Sousa Ramos Félix Silva Miguel. "Analytical study of accelerated light ageing and cleaning effects on acrylic and PVAc dispersion paints used in Modern and Contemporary Art." Doctoral thesis, Universitat Politècnica de València, 2011. http://hdl.handle.net/10251/13829.

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En el trabajo con el título "Analytical study of accelerated light ageing and cleaning effects on acrylic and PVAc dispersion paints used in Modern and Contemporary Art" se han empleado diferentes técncias analíticas con el fin de optimizar protocolos experimentales para la caracterización de la estabilidad de acrílicos y acetatos de polivinilo (PVAc) frente a ensayos de envejecimeinto acelerado y tratamientos de limpieza. El estudio de los procesos de degradación causados por la exposición a la luz se ha desarrollado sobre una amplia seria de muestras acrílicas y vinílicas expuestas a dos tipos de envejecimiento acelerado con condiciones de envejecimiento artificail representativas de un envejecimiento natural. La información química y mecánica obtenida por ambos ensayos de envejecimiento acelerado permitió identificar procesos de degradación específicos tales como entrecruzamiento o escisión de cadenas. Las conclusiones obtenidas de forma general apuntan que los acrílicos son materiales más estables que los vinílicos y los estireno-acrílicos. Asimsismo, en este estudio se han aborado los efectos de los tratamientos de limpieza bien de base acuosa, bien con disolventes orgánicos, en las propiedades físico-qúimicas en muestras acrílicas y vinílicas. También se han evaluado otros métodos de limpieza tales como geles o emulsiones. Los resultados indican que los tratamientos acuosos extraen aditivos, afectan la morfología e inducen cambios en las propiedades mecánicas de las muestras. Estos efectos pueden ser reducidos con el uso de sistemas alternativos de limpieza.
De Sousa Ramos Félix Silva, M. (2011). Analytical study of accelerated light ageing and cleaning effects on acrylic and PVAc dispersion paints used in Modern and Contemporary Art [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/13829
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45

Junior, José Oswaldo de Oliveira. "Efeito analgésico periférico do tramadol em modelo de dor pós-operatória em ratos." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5152/tde-02052016-091403/.

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INTRODUÇÃO: Tramadol é conhecido como um fármaco analgésico de ação central utilizado no tratamento de dores de intensidades moderada a forte. Efeito analgésico local já foi demonstrado. É, em parte, semelhante ao efeito anestésico local, mas outros mecanismos permanecem desconhecidos. O papel de receptores opioides periféricos na analgesia do tramadol na dor pós-operatória não é conhecido. Neste estudo, foi estudado o papel dos receptores opioides no efeito analgésico local do tramadol em modelo de dor por incisão plantar. MÉTODOS: Ratos machos jovens foram submetidos à incisão plantar e no primeiro dia pós-incisão foram divididos em quatro grupos: Grupo IP I-SF/SF - 50 uL de solução de NaCl 0,9% foram injetados na região plantar da pata posterior homolateral à incisão e, 15 minutos depois, novamente injetada a mesma quantidade de solução; Grupo IP II-SF/T_homo - 50 uL de NaCl 0,9% foram injetados na região plantar da pata homolateral e, 15 minutos depois, injetados 50 µL solução contendo 5 mg tramadol; Grupo IP III-SF/T_contra -50 uL de NaCl 0,9% foram injetados na região plantar da pata contralateral e, 15 minutos depois, 50 uL de solução contendo 5 mg de tramadol; Grupo IP IV-Nal/T_homo - 50 uL de solução contendo 200 ug de naloxona foram injetados na pata homolateral e, 15 minutos depois, 50 uL de solução contendo 5mg de tramadol foi injetada. Antes de receberem as injeções, os limiares de retirada da pata por estímulo mecânico produzido por analgesímetro eletrônico de von Frey foram medidos, e, depois da administração dos fármacos, os limiares de retirada foram avaliados nos tempos 15, 30, 45 e 60 minutos após a administração dos fármacos. O mesmo procedimento foi utilizado no segundo dia pós-incisão. As expressões proteicas dos receptores opioide ? (DOR) e µ (MOR) foram avaliadas usando técnica de immunoblotting de gânglios de raízes dorsais homolaterais (L3, L4, L5 e L6) de grupos de animais sem incisão e após 1, 2, 3 e 7 dias de animais submetidos à incisão plantar. RESULTADOS: A incisão plantar gerou marcada hiperalgesia mecânica que foi revertida por tramadol intraplantar nos dois dias. O tramadol intraplantar em pata contralateral não antagonizou a hiperalgesia mecânica, a naloxona antagonizou parcialmente o efeito analgésico do tramadol no primeiro dia pós-incisão, e antagonizou completamente no segundo dia pós-incisão. A expressão proteica de DOR aumentou no 2º, 3º e 7º dias pós-incisão, a expressão de MOR não se modificou. CONCLUSÕES: O tramadol apresentou efeito analgésico local após estímulo mecânico e esse efeito foi antagonizado por naloxona no segundo dia pós-incisão. A expressão de DOR aumentou após a incisão plantar
BACKGROUND: Tramadol is known as a central acting analgesic drugused for the treatment of moderate to severe pain. Local analgesic effect was already demonstrated. It is in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect in postoperative pain is not known. In this study, we examined the role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision pain model. METHODS: Young male Wistar rats were submitted to plantar incision and in the first postoperative day (POD1) were divided into four groups:IP I-SF/SF,50 uL of 0.9% NaCl solution were injected in the plantar aspect of the homolateral hindpaw and again after 15 minutes; IP II-SF/T_homo, 50 uL of 0.9% NaCl solution were injected in the plantar aspect of the homolateral hindpaw and, 15 minutes later, 50 µL of solution containing 5 mg tramadol were injected in the same hindpaw; IP III-SF/T_contra, 50 uL of 0.9% NaCl were injected in the plantar aspect of the contralateral hindpaw and, 15 minutes later, 50 uL of solution containing 5 mg tramadol were injected in the same hindpaw; IP IVNal/T_homo, 50 uL of naloxone (200 ug) solution were injected in the homolateral hindpaw and 15 minutes later 50 µL of solution containing 5 mg tramadol were injected. Before receiving the assigned drugs, baseline withdrawal thresholds for mechanical hyperalgesia using electronic von Frey were measured, then, after receiving the assigned drugs, withdrawal thresholds were measured at 15, 30, 45 and 60 min after drug injection. The same procedure was repeated in POD2. u opioid receptor (MOR) and opioid receptor (DOR) protein expressions were evaluated using immunoblotting after removal of ipsilateral dorsal root ganglia (L3, L4, L5 and L6) in groups of rats non submitted to plantar incision and 1, 2, 3 and 7 days after incision. RESULTS: Plantar incision led to marked mechanical hyperalgesia that was reversed with intraplantar tramadol in both days. Contralateral tramadol did not affect mechanical hyperalgesia and naloxone antagonized partially intraplantar tramadol in POD1, and antagonized completely in POD2. DOR expression in DRGs increased in POD2, POD3 and POD7, MOR expression did not change. CONCLUSIONS: Tramadol presented local analgesic effect after mechanical stimuli and this effect was antagonized by naloxone in the second post incision day. DOR increased expression after plantar incision

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46

Quinn, Francis. "On integrating biomedical and behavioural approaches to activity limitation with chronic pain : testing integrated models between and within persons." Thesis, University of Aberdeen, 2010. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=136667.

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Johnston (1996) proposed that disability can be predicted by a model integrating biomedical and psychological variables; Johnston’s model has mainly been tested in chronic pain and most studies have found it to predict disability better than impairment alone. The first study replicated Dixon’s (2006) structural equation modelling study, which tested an updated variant of Johnston’s model with ICF constructs in orthopaedic patients on a waiting list for joint replacement surgery. The present study also extended these tests to post-surgery. Supportive results were found before surgery, as Dixon had also found, but also after surgery. However, few tests of the model at the within-person level had been conducted. Methodology of published experimental single-case studies targeting behaviour change was investigated in a large systematic review. Studies varied in quality and robustness of design, and few used statistical analyses. Johnston’s model was tested at the within-person level in a series of five correlational single-case studies; whether mood was predictive was also tested. Community participants with arthritis, chronic pain and activity limitations completed a daily dietary using a PDA of pain, activity level, mood and Johnston’s proposed variables, and wore an accelerometer to collect activity data. Differing from previous findings, pain (impairment) was not predictive, nor was self-efficiency, but motivational constructs (intention and goal-setting) did predict activity (limitations) in several cases. PBC predicted in the direction contrary to theory in two cases and was not predictive in the others. Mood was not predictive. Differences from previous findings suggest that the model may not predict the same way within individuals as between them, requiring further investigation.

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47

Herman, David S. "Cholecystokinin in the Rostral Ventromedial Medulla in Models of Neuropathic Pain and Morphine Administration." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/196041.

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States of abnormal pain induced by injuries to peripheral nerves share common features with opioid antinociceptive tolerance including mechanical and thermal hypersensitivity. Sustained administration of morphine in humans and in animals induces a state of abnormal pain (i.e., hyperalgesia) and may be associated with the development opioid antinociceptive tolerance. Persistent neuropathic pain states and opioid induced abnormal pain require descending facilitation arising from the rostral ventromedial medulla (RVM). Cholecystokinin (CCK), a pronociceptive peptide, may be up-regulated following opioid treatment and nerve injury in the brain and spinal cord. Therefore, it is hypothesized that CCK in the RVM may be up-regulated by sustained opioid administration and my consequently drive descending pain facilitatory mechanisms to produce hypersensitivity and antinociceptive tolerance.Acute systemic morphine administration produced a potentiation of CCK release in the RVM as measured using microdialysis techniques. Sustained systemic morphine administration sufficient to produce thermal and tactile hypersensitivity resulted in a significant increase in basal CCK release in the RVM. Spinal nerve ligation (SNL) produces similar behavioral hypersensitivity. CCK levels in the RVM also increased following SNL. These findings suggest that endogenous CCK released in the RVM drives descending facilitatory pathways to produce hypersensitivity following sustained morphine administration and neuropathic pain.Disease states such as neuropathic pain offer special challenges in drug design due to system changes that accompany these diseases. Here, novel peptides with agonist binding affinity and bioactivity at δ and μ opioid receptors and simultaneous antagonist activity at CCK receptors have been developed. Using in vivo behavioral measures, it was shown that intrathecal (i.th.) administration of these compounds suppresses the thermal and tactile hypersensitivity caused by spinal nerve ligation (SNL).These studies support the hypothesis that endogenous CCK drives descending pain facilitatory pathways and that bi-functional compounds that act as opioid agonists and CCK antagonists are effective for the treatment of neuropathic pain.

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48

Bishop, James Hart. "Imaging Pain And Brain Plasticity: A Longitudinal Structural Imaging Study." ScholarWorks @ UVM, 2017. http://scholarworks.uvm.edu/graddis/786.

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Chronic musculoskeletal pain is a leading cause of disability worldwide yet the mechanisms of chronification and neural responses to effective treatment remain elusive. Non-invasive imaging techniques are useful for investigating brain alterations associated with health and disease. Thus the overall goal of this dissertation was to investigate the white (WM) and grey matter (GM) structural differences in patients with musculoskeletal pain before and after psychotherapeutic intervention: cognitive behavioral therapy (CBT). To aid in the interpretation of clinical findings, we used a novel porcine model of low back pain-like pathophysiology and developed a post-mortem, in situ, neuroimaging approach to facilitate translational investigation. The first objective of this dissertation (Chapter 2) was to identify structural brain alterations in chronic pain patients compared to healthy controls. To achieve this, we examined GM volume and diffusivity as well as WM metrics of complexity, density, and connectivity. Consistent with the literature, we observed robust differences in GM volume across a number of brain regions in chronic pain patients, however, findings of increased GM volume in several regions are in contrast to previous reports. We also identified WM changes, with pain patients exhibiting reduced WM density in tracts that project to descending pain modulatory regions as well as increased connectivity to default mode network structures, and bidirectional alterations in complexity. These findings may reflect network level dysfunction in patients with chronic pain. The second aim (Chapter 3) was to investigate reversibility or neuroplasticity of structural alterations in the chronic pain brain following CBT compared to an active control group. Longitudinal evaluation was carried out at baseline, following 11-week intervention, and a four-month follow-up. Similarly, we conducted structural brain assessments including GM morphometry and WM complexity and connectivity. We did not observe GM volumetric or WM connectivity changes, but we did discover differences in WM complexity after therapy and at follow-up visits. To facilitate mechanistic investigation of pain related brain changes, we used a novel porcine model of low back pain-like pathophysiology (Chapter 6). This model replicates hallmarks of chronic pain, such as soft tissue injury and movement alteration. We also developed a novel protocol to perform translational post-mortem, in situ, neuroimaging in our porcine model to reproduce WM and GM findings observed in humans, followed by a unique perfusion and immersion fixation protocol to enable histological assessment (Chapter 4). In conclusion, our clinical data suggest robust structural brain alterations in patients with chronic pain as compared to healthy individuals and in response to therapeutic intervention. However, the mechanism of these brain changes remains unknown. Therefore, we propose to use a porcine model of musculoskeletal pain with a novel neuroimaging protocol to promote mechanistic investigation and expand our interpretation of clinical findings.

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DEMARTINI, CHIARA. "The role of TRPA1 and TRPV1 channels in trigeminal pain: data from animal models." Doctoral thesis, Università degli studi di Pavia, 2018. http://hdl.handle.net/11571/1214824.

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Experimental and clinical observations pointed out a critical involvement of transient receptor potential (TRP) channels, particularly TRPA1 and TRPV1, in trigeminal pain and associated symptoms, including hyperalgesia and allodynia. In this study the role of TRP channels was investigate in two animal models of diseases related to the trigeminal system: migraine and trigeminal neuropathic pain (TNP). TRPA1 and TRPV1 antagonists (ADM_12 and AMG9810 respectively) were used in the nitroglycerin (NTG)-induced hyperalgesia at the trigeminal level induced by means of the orofacial formalin test, a well validated animal model of migraine. The behavioral effects of AMG9810 gave inconclusive results, probably because its effect was confounded by the vehicle used. Nonetheless, it appears that TRPV1 channels are somehow involved in NTG-induced trigeminal hyperalgesia, since the TRPV1 mRNA levels were found to be strongly increased after NTG injection in medulla, cervical spinal cord and trigeminal ganglia (TG). NTG also up-regulated the mRNA levels of TRPA1, c-fos, calcitonin gene-related peptide (CGRP) and Substance P (SP) in the same areas. Those transcripts, but TRPV1, were reduced after ADM_12 treatment, which abolished the NTG-induced trigeminal hyperalgesia. The increased availability of nitric oxide after NTG promotes the formation of pro-inflammatory agents which can activate and/or sensitize nociceptors by means of TRPA1 and TRPV1 channels, causing the release of CGRP and SP. Although no differences in CGRP and SP protein expression were found at nucleus trigeminalis caudalis (NTC) level, the increased transcripts may reflect compensatory mechanisms aimed at reintegrating CGRP and SP stores depleted after NTG administration. It is possible that ADM_12 caused a reduction of Ca2+ influx through TRPA1 channels, which in turn interfered with the cascade of second-messenger molecules and with the Ca2+-interacting proteins, ultimately preventing NTG-induced inflammatory pathways. For TNP, the role of TRPA1 channels (by means of ADM_12) was investigated by evaluating mechanical allodynia in a model of chronic constriction injury of the infraorbital nerve (IoN-CCI). The IoN-CCI rats showed a hyperresponsiveness (4 weeks after surgery) at the ipsilateral side that reflects a condition of mechanical allodynia, and a significant increase in TRPA1, TRPV1, CGRP and SP mRNA expression levels. Although a tendency towards a decrease was seen in the ipsilateral compared to the contralateral side in the IoN-CCI rats, no significant differences in CGRP and SP protein expression at the NTC level were seen. However, their transcripts were highly increased in the central areas containing the NTC, as well as the TG ipsilateral to the IoN ligation. Both the allodynic response and the increased mRNA levels of operated rats were abolished after ADM_12 treatment. Probably, the blockade of TRPA1 channels located on the trigeminal afferents prevented neuropeptides release thus resulting in a reduced neurogenic inflammation and the nociceptors sensitization. Contrary to the migraine model, ADM_12 reduced transcript levels of both TRPs in IoN-CCI rats. Thus, ADM_12 appears to be a specific antagonist for TRPA1 in migraine pain, but in TNP it seems to act also on TRPV1. Probably, the damage induced by the nerve injury lead to a re-organization in expression and nature of the channels that made ADM_12 able to block TRPV1 channels. Since TRPA1 and TRPV1 are functionally linked, ADM_12 could have a direct effect on TRPA1 and an indirect effect on TRPV1 channels. In conclusion, TRPA1 blockade might be useful in the treatment of these trigeminal pain disorders. Moreover, our data suggest an important role also for TRPV1 channels, which could be differently involved depending on the type of pain. Further exploration on the mechanisms underlying the antinociceptive effects of these TRPs should improve our understanding of trigeminal pain processing.
Experimental and clinical observations pointed out a critical involvement of transient receptor potential (TRP) channels, particularly TRPA1 and TRPV1, in trigeminal pain and associated symptoms, including hyperalgesia and allodynia. In this study the role of TRP channels was investigate in two animal models of diseases related to the trigeminal system: migraine and trigeminal neuropathic pain (TNP). TRPA1 and TRPV1 antagonists (ADM_12 and AMG9810 respectively) were used in the nitroglycerin (NTG)-induced hyperalgesia at the trigeminal level induced by means of the orofacial formalin test, a well validated animal model of migraine. The behavioral effects of AMG9810 gave inconclusive results, probably because its effect was confounded by the vehicle used. Nonetheless, it appears that TRPV1 channels are somehow involved in NTG-induced trigeminal hyperalgesia, since the TRPV1 mRNA levels were found to be strongly increased after NTG injection in medulla, cervical spinal cord and trigeminal ganglia (TG). NTG also up-regulated the mRNA levels of TRPA1, c-fos, calcitonin gene-related peptide (CGRP) and Substance P (SP) in the same areas. Those transcripts, but TRPV1, were reduced after ADM_12 treatment, which abolished the NTG-induced trigeminal hyperalgesia. The increased availability of nitric oxide after NTG promotes the formation of pro-inflammatory agents which can activate and/or sensitize nociceptors by means of TRPA1 and TRPV1 channels, causing the release of CGRP and SP. Although no differences in CGRP and SP protein expression were found at nucleus trigeminalis caudalis (NTC) level, the increased transcripts may reflect compensatory mechanisms aimed at reintegrating CGRP and SP stores depleted after NTG administration. It is possible that ADM_12 caused a reduction of Ca2+ influx through TRPA1 channels, which in turn interfered with the cascade of second-messenger molecules and with the Ca2+-interacting proteins, ultimately preventing NTG-induced inflammatory pathways. For TNP, the role of TRPA1 channels (by means of ADM_12) was investigated by evaluating mechanical allodynia in a model of chronic constriction injury of the infraorbital nerve (IoN-CCI). The IoN-CCI rats showed a hyperresponsiveness (4 weeks after surgery) at the ipsilateral side that reflects a condition of mechanical allodynia, and a significant increase in TRPA1, TRPV1, CGRP and SP mRNA expression levels. Although a tendency towards a decrease was seen in the ipsilateral compared to the contralateral side in the IoN-CCI rats, no significant differences in CGRP and SP protein expression at the NTC level were seen. However, their transcripts were highly increased in the central areas containing the NTC, as well as the TG ipsilateral to the IoN ligation. Both the allodynic response and the increased mRNA levels of operated rats were abolished after ADM_12 treatment. Probably, the blockade of TRPA1 channels located on the trigeminal afferents prevented neuropeptides release thus resulting in a reduced neurogenic inflammation and the nociceptors sensitization. Contrary to the migraine model, ADM_12 reduced transcript levels of both TRPs in IoN-CCI rats. Thus, ADM_12 appears to be a specific antagonist for TRPA1 in migraine pain, but in TNP it seems to act also on TRPV1. Probably, the damage induced by the nerve injury lead to a re-organization in expression and nature of the channels that made ADM_12 able to block TRPV1 channels. Since TRPA1 and TRPV1 are functionally linked, ADM_12 could have a direct effect on TRPA1 and an indirect effect on TRPV1 channels. In conclusion, TRPA1 blockade might be useful in the treatment of these trigeminal pain disorders. Moreover, our data suggest an important role also for TRPV1 channels, which could be differently involved depending on the type of pain. Further exploration on the mechanisms underlying the antinociceptive effects of these TRPs should improve our understanding of trigeminal pain processing.

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50

Siedlecki, Sandra. "The effect of music on power, pain, depression, and disability a clinical trial /." Connect to text online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1093526080.

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Dissertations / Theses on the topic 'Modern paint'

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