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1

Holaday, John W. Endogenous opioids and their receptors. Kalamazoo, Mich: Upjohn, 1985.

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2

Marcello, Negri, Lotti G, and Grossman Ashley, eds. Clinical perspectives of endogenous opioids production. Chichester: J. Wiley, 1992.

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3

Browning, Andrew J. F. Endogenous opioid peptides and human reproduction. Birmingham: University of Birmingham, 1985.

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4

Salansky, Norman. Endogenous opioid peptide level changes under electrostimulation and their assessment by the EEG. Downsview, Ontario: [s.n.], 1994.

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5

Sommer, Claudia. Endogenous opioids mediate stress-induced analgesia. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0031.

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This chapter reviews the landmark paper published in 1990 by Stein et al. and entitled ‘Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation’. Opioids, besides acting centrally as analgesics, may act peripherally upon opioid receptors located on axons and on immune cells. In the publication by Stein et al., it was shown for the first time that endogenous opioid peptides released from immune cells mediate stress-induced analgesia, potentially through opioid receptors on peripheral nerve endings. This finding has led to numerous follow-up studies on endogenous analgesia, including work showing that cannabinoid analgesia is mediated via the peripheral release of opioids, and to the concept of topical opioid analgesia, which may be a good way of using the potent analgesia that opioids can convey, without their CNS-associated side effects.
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6

Dickenson, Tony. Endogenous opioids in the CNS. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0019.

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This short and concise paper was the first to unequivocally reveal that there were endogenous opioids in the central nervous system (CNS), identify their peptide nature and sequence, and show that they exerted physiological inhibitory effects. The idea that there were natural opioids fitted with concurrent reports of opiate-binding sites, and this led to the description of multiple receptors with their own families of peptide transmitters. No truly novel opioid drugs have emerged since, and attempts to protect and manipulate the enkephalins for pain control have yet to be successful. This does not detract from this key study, which made us think about pain modulation in a different way, and subsequent work has clearly shown how endogenous opioid signalling is critical in CNS function, perhaps most importantly in endogenous pain control, such as that harnessed by placebo analgesia.
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7

Taylor, Véronique A., and Pierre Rainville. Endogenous opioids in placebo-induced analgesia. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0011.

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Placebos achieve scientifically proven pain-relieving effects yet are inactive substances for the treatment of pain. Levine, Gordon, and Fields were the first to demonstrate the role of endogenous opioids in placebo-induced analgesia during dental post-operative pain. Several studies using pharmacological manipulations and/or neuroimaging techniques confirmed their findings that placebo analgesia is reversible by naloxone, and also identified brain pathways involved in opioidergic neurotransmission during placebo analgesia (prefrontal regions rich in opioid receptors such as the anterior cingulate cortex, presumably initiating descending pain modulation through downstream projections to the brainstem). Fifty years of research in pharmacology and neurobiology have contributed to the identification of physical as well as psychological determinants of placebo analgesia. Expectations of pain relief are maintained by conditioned learning and reward-related processes, reflected by interactions between different neurotransmitters (opioids, dopamine, endocannabinoids) in a variety of brain circuits related to executive/cognitive processes as well as affect and reward.
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8

Bird, Mark F., and David G. Lambert. Deorphanization of ORL-1/LC132 by reverse pharmacology in two landmark studies. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0026.

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Deorphanization of ORL-1/LC132 in 1995 by reverse pharmacology in two simultaneously published landmark studies added a new member to the opioid family of G-protein coupled receptors. Meunier and Reinscheid used cells expressing recombinant ORL-1 (human) or LC132 (rat) and the presumed intracellular inhibition of cyclic AMP formation to ‘fish’ for endogenous peptide ligands in rat whole-brain and pig hypothalamic extracts. Both studies reported the isolation of a 17-amino-acid peptide, which was named nociceptin and orphanin FQ by the two authors, respectively. The behaviour of the isolated peptide was a complete surprise, as a general hyperalgesia was observed when the peptide was administered at supraspinal sites. We now know that this peptide has, in fact, anti-opioid action, particularly in the medulla. The endogenous peptide exerts a multitude of effects both in the nervous system and, unlike classical opioids, has efficacy in neuropathic pain.
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9

Bromley, Lesley. The molecular basis for the placebo effect. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0041.

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The landmark paper discussed in this chapter is ‘The neurobiology of placebo analgesia: From endogenous opioids to cholecystokinin’, published by Benedetti and Amanzio in 1997. This major review considered the placebo and nocebo effect in a more scientific framework compared to previous treatise of a nebulous concept whose only role is to act as a comparator for controlled trials. By expounding robust evidence, Benedetti and Amanzio added credence to the placebo effect, with not just psychological but also physiological data, acknowledging it as an effective therapeutic action. Furthermore, the importance of endogenous opioids and cholecystokinin in the mechanism of placebo were put into sharp relief, giving an intuitive basis and scientific validation to this effect.
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10

Simon, Eric J., and Hiroshi Takagi. Advances in Endogenous and Exogenous Opioids: Proceedings of the International Narcotic Research Conference Held in Kyoto, Japan on July 26-30 1981. Elsevier, 2013.

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11

Negri, Marcello, and Gaetano Lotti. Clinical Perspectives of Endogenous Opioid Peptides. John Wiley & Sons, 1992.

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12

Ashley, Grossman, Lotti G, and Negri Marcello, eds. Clinical perspectives in endogenous opioid peptides. Chichester: J. Wiley, 1992.

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13

Laycock, Helen. Nocebo and its importance in clinical practice. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0045.

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The landmark paper discussed in this chapter is ‘When words are painful: unravelling the mechanism of the nocebo effect’, published in 2007 by Benedetti et al. This major review considered the placebo and nocebo effect in a more scientific framework compared to the previous nebulous concept of a placebo as an agent whose only role is was to act as a comparator for controlled trials. By expounding robust evidence, Benedetti added credence to the placebo effect with not just psychological but physiological data acknowledging it as an effective therapeutic action. Furthermore the importance of endogenous opioids and cholecystokinin in the mechanism underlying the relief of pain by placebos was put into sharp relief, giving an intuitive basis and scientific validation to this effect.
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14

El-Tayeb, Kamal Mohammed Ahmed. The role of the endogenous opioid peptides in glucoregulation. 1985.

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15

Patel, Dinesh. Structural and pharmacological studies of synthetic and endogenous opioid receptor ligands. 1992.

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16

Bell, Katrina Margaret. A biochemical and pharmacological characterisation of some endogenous and exogenous k opioid ligands. 1994.

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17

Carpenter, Gregory, and Meenal Patil. Gender Differences in Pain. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190217518.003.0005.

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Epidemiologic and clinical findings demonstrate that women are at increased risk for chronic pain, experience greater pain-related distress, and show heightened sensitivity for pain compared to men. There are differences in analgesic responses to pain and to both opioid and non-opioid medications as well as for endogenous analgesic processes. Many stress-related disorders, such as fibromyalgia and chronic pain, are more prevalent in women. Studies of experimentally induced pain show that women exhibit greater pain sensitivity, enhanced pain facilitation, and reduced pain inhibition compared to men. Mechanisms that implicated in the underlying sex differences include biological involvement of estrogen and progesterone versus testosterone. Sex-related differences in pain may also reflect differences in the endogenous opioid system. Other mechanisms include steroid action differences in adulthood, modulation of various biological systems such as the cardiovascular and inflammatory pathways, and sociocultural differences
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18

Tsagareli, Merab G. Antinociceptive Tolerance to NSAIDs in Brain Limbic Areas: Role of Endogenous Opioid and Cannabinoid Systems. Nova Science Publishers, Incorporated, 2021.

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19

Tsagareli, Merab G. Antinociceptive Tolerance to NSAIDs in Brain Limbic Areas: Role of Endogenous Opioid and Cannabinoid Systems. Nova Science Publishers, Incorporated, 2021.

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20

Velasco, Ana Isabel Martín. Respuesta de Las Gonadotropinas Al Estrés: Papel de Las Catecolamina la Crh y Los Opioides Endogenos. Universidad Complutense de Madrid, Servicio de Publicaciones, 2006.

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21

Gerhard, Gwenyth Gravlin. THE RELATIONSHIPS AMONG HABITUAL PHYSICAL ACTIVITY, ENDOGENOUS OPIOID LEVELS, AND SUBSEQUENT ACUTE SURGICAL PAIN EXPERIENCES (ENDORPHIN, VISUAL ANALOG SCALING). 1985.

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22

Soloff, Paul, and Christian Schmahl. Suicide and Nonsuicidal Self-Injury. Edited by Christian Schmahl, K. Luan Phan, Robert O. Friedel, and Larry J. Siever. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199362318.003.0011.

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This chapter reviews current data on the prevalence of suicidal behavior and non-suicidal self-injury (NSSI) in patients with PDs; the characteristics of attempters versus completers; and the epidemiology of NSSI in borderline personality disorder (BPD). In addition, it presents explanatory models for suicide and NSSI. Also, there are comprehensive discussions of the neurobiological mechanisms involved in both suicidality and NSSI focusing on the structural and functional neuroimaging of emotion dysregulation, impulsivity, executive cognitive deficits, affective interference and cognitive function, and the Endogenous Opioid System. The chapter concludes with a detailed description of pain processing as it interacts with NSSI.
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23

Carrión, Victor G., John A. Turner, and Carl F. Weems. Dissociation. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190201968.003.0004.

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Dissociation is a neurological state of acute disconnection with the reality of a situation or the self, and is often observed in PTSD. Because of its broad definition, diverse expression, and frequent comorbidity with other disorders, dissociation remains a challenging phenomenon to research and treat. The current chapter reviews the small amount of preclinical literature that has laid the groundwork of our understanding of the physiological underpinnings of dissociation, including theories of its mechanization of the endogenous opioid system. The challenges and importance of assessing dissociation are discussed, and the current instruments available for this assessment are reviewed. The experience of childhood sexual abuse has been specifically linked to the development of dissociative symptoms in PTSD. Future directions, including suggestions for categorical approaches to the identification and treatment of dissociative symptoms, are discussed.
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24

Randall, Jill I. Behavioural and neurochemical mechanisms of social conflict analgesia in mus musculus: Involvement of endogenous opioid and benzodiazepire substiates in two situation-dependent forms of social conflict analgesia in male laboratory mice. Bradford, 1988.

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