Academic literature on the topic 'Axon reflex response'

Physiology textbooks almost always include the axon reflex in the context of the triple response, often followed by the caveat that the evidence is either indirect or incomplete. Experimental work and ideas on the topic are reviewed, asking whether there now is a stronger case for axon reflex mechanisms.

The whole-body shortening reflex of the medicinal leech Hirudo medicinalis is a withdrawal response produced by anterior mechanical stimuli. The interneuronal pathways underlying this reflex consist of the S cell network (a chain of electrically coupled interneurons) and a set of other, parallel pathways. We used a variety of techniques to characterize these interneuronal pathways further, including intracellular stimulation of the S cell network, photoablation of the S cell axon, and selective lesions of particular connectives (the axon bundles that link adjacent ganglia in the leech nerve cord). These experiments demonstrated that the S cell network is neither sufficient nor necessary for the production of the shortening reflex. The axons of the parallel pathways were localized to the lateral connectives (whereas the S cell axon runs through the medial connective). We used physiological techniques to show that the axons of the parallel pathways have a larger diameter in the anterior connective and to demonstrate that the parallel pathways are activated selectively by anterior mechanosensory stimuli. We also presented correlative evidence that the parallel pathways, along with activating motor neurons during shortening, are responsible for inhibiting a higher-order “command-like” interneuron in the neuronal circuit for swimming, thus playing a role in the behavioral choice between swimming and shortening.

The mechanisms underlying the skin blood flow (SkBF) response to local heating are complex and poorly understood. Our goal was to examine the role of axon reflexes and nitric oxide (NO) in the SkBF response to a local heating protocol. We performed 40 experiments following a standardized heating protocol with different interventions, including blockade of the axon reflex (EMLA cream), antebrachial nerve blockade (0.5% bupivacaine injection), and NO synthase (NOS) inhibition (≥10 mM N G-nitro-l-arginine methyl ester; microdialysis). Appropriate controls were performed to verify the efficacy of the various blocks. Values are expressed as a percentage of maximal SkBF (SkBFmax; 50 mM sodium nitroprusside). At the initiation of local heating, SkBF rose to an initial peak, followed by a brief nadir, and a secondary, progressive rise to a plateau. Axon reflex block decreased the initial peak from 75+3 to 32 ± 2% SkBFmax ( P< 0.01 vs. control) but did not affect the plateau. NOS inhibition before and throughout local heating reduced the initial peak from 75 ± 3 to 56 ± 3% SkBFmax ( P< 0.01) and the plateau from 87 ± 4 to 40 ± 5%. NOS inhibition during axon reflex block did not further reduce the initial SkBF peak compared with axon reflex block alone. Antebrachial nerve block did not affect the local heating SkBF response. The primary finding of these studies is that there are at least two independent mechanisms contributing to the rise in SkBF during nonpainful local heating: a fast-responding vasodilator system mediated by the axon reflexes and a more slowly responding vasodilator system that relies on local production of NO.

Objectives The aim of the present study was to elucidate the mechanism of cutaneous vasodilation following acupuncture stimulation by investigating the roles of nitric oxide (NO) and axon reflex vasodilation. Methods The subjects were 17 healthy male volunteers. The role of NO was investigated by administering NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 20 mM), an NO synthase inhibitor or Ringer's solution (control site), via intradermal microdialysis (protocol 1; n=7). The role of axon reflex vasodilation by local sensory neurones was investigated by comparing vasodilation at sites treated with ‘eutectic mixture of local anaesthetics’ (EMLA) cream (2.5% lidocaine and 2.5% prilocaine) with untreated sites (control site) (protocol 2; n=10). After 5 min of baseline recording, acupuncture was applied to PC4 and a control site in proximity to PC4 for 10 min and scanning was performed for 60 min after acupuncture stimulation. Skin blood flow (SkBF) was evaluated by laser Doppler perfusion imaging. Cutaneous vascular conductance (CVC) was calculated from the ratio of SkBF to mean arterial blood pressure. Results In the first protocol, sites administered L-NAME showed significant reductions in CVC responses following acupuncture stimulation compared to control sites (administered Ringer's solution) (p<0.05). In the second protocol, changes in CVC responses after acupuncture stimulation did not differ significantly between treated sites with EMLA cream and untreated sites (p>0.05). Conclusions These data suggest that cutaneous vasodilation in response to acupuncture stimulation may not occur through an axon reflex as previously reported. Rather, NO mechanisms appear to contribute to the vasodilator response.

Cutaneous vasodilation is reduced in healthy older vs. young subjects; however, the mechanisms that underlie these age-related changes are unclear. Our goal in the present study was to determine the role of nitric oxide (NO) and the axon reflexes in the skin blood flow (SkBF) response to local heating with advanced age. We placed two microdialysis fibers in the forearm skin of 10 young (Y; 22 ± 2 yr) and 10 older (O; 77 ± 5 yr) men and women. SkBF over each site was measured by laser-Doppler flowmetry (LDF; Moor DRT4). Both sites were heated to 42°C for ∼60 min while 10 mM N G-nitro-l-arginine methyl ester (l-NAME) was infused throughout the protocol to inhibit NO synthase (NOS) in one site and 10 mM l-NAME was infused after 40 min of local heating in the second site. Data were expressed as a percentage of maximal vasodilation (%CVCmax; 28 mM nitroprusside infusion). Local heating beforel-NAME infusion resulted in a significantly reduced initial peak (Y: 61 ± 2%CVCmax vs. O: 46 ± 4%CVCmax) and plateau (Y: 93 ± 2%CVCmaxvs. O: 82 ± 5%CVCmax) CVC values in older subjects ( P < 0.05). When NOS was inhibited after 40 min of heating, CVC declined to the same value in the young and older groups. Thus the overall contribution of NO to the plateau phase of the SkBF response to local heating was less in the older subjects. The initial peak response was significantly lower in the older subjects in both microdialysis sites (Y: 52 ± 4%CVCmax vs. O: 38 ± 5%CVCmax; P < 0.05). These data suggest that age-related changes in both axon reflex-mediated and NO-mediated vasodilation contribute to attenuated cutaneous vasodilator responses in the elderly.

Abstract Background: Complex regional pain syndrome is multifactorial. Exaggerated inflammatory responses to limb injury may be involved. The authors hypothesized that capsaicin-induced pain and neurogenic inflammation (skin perfusion and flare area) are increased in patients with complex regional pain syndrome compared with that in controls. Methods: Twenty patients with unilateral upper-limb complex regional pain syndrome and 20 age-, sex-, and body mass index–matched controls participated. Topical capsaicin 5% was applied to the back of both hands for 30 min, and pain intensity was assessed on a visual analogue scale. A laser Doppler perfusion imager scanner estimated capsaicin-induced skin perfusion and flare area. Autonomic and small-fiber function was assessed by sensory testing, quantitative sudomotor axon reflex test, and vasoconstrictor responses. Results: The authors found bilateral hypersensitivity to capsaicin (P ≤ 0.02), skin fold (P = 0.001), joint pressure (P &lt; 0.0001), cold (P ≤ 0.01), and heat pain (P ≤ 0.04) in patients compared with that in controls and thermal and mechanical hyperalgesia in the complex regional pain syndrome–affected hand compared with that in the unaffected hand (P ≤ 0.001). The patients had normal capsaicin-induced flare areas, thermal detection thresholds, quantitative sudomotor axon reflex test, and vasoconstrictor responses. Conclusions: The main finding is bilaterally increased capsaicin-induced pain in patients compared with controls. The flare response to capsaicin was normal, suggesting that the increased pain response was not due to increased neurogenic inflammation. The bilateral hypersensitivity to painful chemical, thermal, and mechanical stimuli not confined to the innervation area of a peripheral nerve or root cannot be explained by a regional change and may partly be due to central sensitization.

Abstract The aim of the study was to evaluate the changes in skin blood flow as a result of local heating tests in migraine patients during the interictal period, measured by laser Doppler perfusion imaging (LDI). The aim of the study was also to estimate the correlations between the results of these tests and interleukin (IL)-8 levels. Twelve migraine patients during their interictal period were compared with twelve healthy control subjects. Only women were included in the study. Both groups were matched with regard of their age, body mass index and blood pressure. For the purpose of measuring cutaneous microvascular blood flow, heating (+44 °C) of the dorsal side of the palm as a response to the local LDI was used. IL-8 was measured in serum by ELISA method. The findings suggested that migraine patients have a cutaneous vasomotor dysfunction during the interictal period. The results showed a significant decrease in the initial peak of vasodilation and the second peak of vasodilation (plateau phase). Also there were significant changes observed in the length of the time interval required to reach the first and second vasodilation peak. It is known that migraine patients have a shorter time interval to reach the first perfusion peak (axonal reflex-mediated) and longer time interval to reach the second peak (endothelium-dependent). The results confirmed the correlation between proinflammatory chemokine IL-8 levels, and the time interval till the second peak of blood flow in all study subjects.

Rosacea is a chronic skin disorder, characterized by redness and flushing of the cheeks, nose, chin or forehead. It has been proposed that rosacea is a result of frequent blushing (Miller, 1921; Klaber & Whittkower, 1939). However, the relationship between rosacea and blushing is uncertain. The aim of the present research was to investigate the relationship between psychological stress and vascular disturbances in rosacea. Five studies were conducted. The first study explored the relationship between rosacea and mental health while the next two investigated vascular responses in rosacea sufferers and controls to acetylcholine (which induces endothelial vasodilatation and axon reflexes) and psychological stress (embarrassment). The fourth study aimed to examine the relationship between psychological indicators and rosacea symptoms on a daily basis. The fifth study consisted of three case studies looking at the use of Cognitive Behavioural Therapy (CBT) and Task Concentration Training (TCT) with rosacea sufferers presenting with social anxiety and fear of blushing symptoms. In study 1, sixty-two participants were asked to complete the Blushing Propensity Scale (BPS), Fear of Negative Evaluation (FNE), Depression, Anxiety and Stress Scale (DASS), Social Interaction Anxiety Scale (SIAS) and Social Phobia Scale (SPS). Outcomes from the first study indicated that Type 2 rosacea sufferers (n= 12) perceived themselves as blushing more frequently and intensely than Type 1 rosacea sufferers (n=19) or controls (n=31). This suggested that Type 2 rosacea sufferers experiencing frequent blushing may have a lower sensitivity threshold to blushing episodes. In addition, Type 2 rosacea sufferers perceived themselves as more stressed than Type 1 rosacea sufferers or controls, possibly indicating that managing the condition can be stressful. Contrary to previous reports (Gupta et al., 2006; National Rosacea Society, 2005) severity of rosacea was not associated with depression, social anxiety or fear of negative evaluation. However, a few participants who reported high social anxiety and stress scores were offered psychological intervention (Study 5). The aim of the second study was to investigate vascular responses in rosacea sufferers. Cutaneous endothelial and axon reflex function was assessed using an acetylcholine dose response curve. The axon reflex was assessed by inducing a flare with ACh iontophoresis. Outcomes from this study indicated that Type 2 rosacea sufferers had a greater axon reflex response than Type 1 rosacea sufferers. Thus over-reactivity of the axon reflex in Type 2 rosacea sufferers might contribute to prolonged vasodilatation. However, cutaneous endothelial responses to ACh were similar in rosacea and control groups. The results suggested that neural pathways mediated the flushing response rather than cutaneous endothelial function. The third study investigated facial blood flow while participants attempted laboratory induced embarrassment tasks. Type 2 rosacea sufferers were found to have a greater blood flow in the facial region than Type 1 rosacea sufferers during singing and speech tasks, suggesting that Type 2 rosacea sufferers blushed more than type 1 rosacea sufferers or controls. Furthermore, Type 2 rosacea sufferers reported higher embarrassment and blushing ratings than Type 1 rosacea sufferers. This indicated that Type 2 rosacea sufferers perceived themselves as emotionally more aroused than other participants. Taken together, it would appear that a combination of physiological and cognitive factors increased facial blood flow in Type 2 rosacea sufferers in laboratory induced embarrassment tasks. The fourth study explored the relationship between stress and symptoms of rosacea. Using a diary, 15 rosacea sufferers recorded their stress, anxiety and mood and their intensity of rosacea symptoms daily. Stress was associated with increased stinging/facial redness on the same day for 1 to 2 months. Furthermore, it was associated with increased stinging ratings the next day. However, feeling anxious or having low mood was not related to increase stinging the next day. The presence of increased stress found in rosacea participants on the day where stinging and redness occurred should be taken into consideration when formulating psychological interventions for rosacea sufferers. In study 5, individual psychological intervention was provided to three participants experiencing stress, fear of blushing and social anxiety symptoms. Cognitive Behavioural Therapy (CBT) and Task Concentration Training (TCT) were helpful in managing stress, anxiety and fear of blushing symptoms in individual rosacea sufferers. Encouragingly, all participants reported a gain in their repertoire of strategies and showed a decrease in anxiety symptoms on assessment questionnaires following their intervention. Replication of the intervention protocol and investigation of other psychological approaches are required to establish best practise outcome for rosacea sufferers who require psychological interventions. The present findings suggest that over-reactivity of axon reflexes contributes to facial flushing. In addition, emotional flushing in rosacea sufferers appears to be maintained by a combination of cognitive and physiological factors. On a clinical level, the study recommends that emotional stress associated with facial flushing in rosacea sufferers to be targeted for psychological intervention.

The motor unit represent the final output of the motor system. Each consists of a motoneuron, its axon, neuromuscular junctions, and muscle fibres innervated by that axon. The discharge of a motor unit can be followed by recording its electromyographic signature, the motor unit action potential. Motoneurons are not passive responders to the excitatory and inhibitory influences on them from descending and segmental sources. Their properties can change, e.g. due to descending monoaminergic pathways, which can alter their responses to other inputs (changing ‘reflex gain’). Contraction strength depends on the number of active motor units, their discharge rate, and whether the innervated muscle fibres are slow-twitch producing low force, but resistant to fatigue, fast-twitch producing more force, but susceptible to fatigue, or intermediate fast-twitch fatigue-resistant. These properties are imposed by the parent motoneurons, and the innervated muscle fibres have different histochemical profiles (oxidative, glycolytic, or oxidative-glycolytic, respectively).

The application of noninvasive, sensitive, quantitative, and dynamic tests of sudomotor function enhances significantly our ability to quantitate one aspect of the autonomic deficit. The QSART has an important role in clinical applications to better definition of the course of neuropathy, its response to treatment, and further exploration of sudomotor physiology.

Small distal nerve fibers are often selectively involved in some patients with axonal neuropathies (distal small-fiber neuropathy). One method of testing the integrity of these small nerve fibers is to study the postganglionic sympathetic sudomotor “C” fiber function. The application of noninvasive, sensitive, quantitative, and dynamic tests of sudomotor function significantly enhances the ability to quantitate one aspect of the autonomic deficit. The quantitative sudomotor axon reflex test (QSART) has an important role in clinical applications to better definition of the course of neuropathy, its response to treatment, and further exploration of sudomotor physiology. Simpler methods are available as screening tests. This chapter reviews the use of methods to measure sudomotor fiber function.

Late responses are a group of responses occurring after the compound muscle action potential (M-wave) in motor nerve conduction studies and include F-waves, H-reflexes, and axon reflexes. These responses can indirectly measure aspects of proximal conduction that are not obtained with routine motor nerve conduction studies and may be useful in assessing diseases that affect proximal nerves, such as polyradiculopathies. A thorough understanding of the physiological basis, sources of error, and clinical applications and limitations enhances the usefulness of F-waves and H-reflexes as one means to evaluate proximal functioning of the motor and sensory nerves. This chapter will discuss the study methods and applications of F-waves and H-reflexes.

The cornerstone of modern biophysics is the comprehensive analysis by Hodgkin and Huxley (1952a,b,c,d) of the generation and propagation of action potentials in the squid giant axon. The basis of their model is a fast sodium current INa and a delayed potassium current IK (which here we also refer to as IDR)- The last 40 years of research have shown that impulse conduction along axons can be successfully analyzed in terms of one or both of these currents. Nonetheless, their equations do not capture—nor were they intended to capture—a number of important biophysical phenomena, such as adaptation of the firing frequency to long-lasting stimuli or bursting, that is, the generation of two to five spikes within 5-20 msec. Moreover, the transmission of electrical signals within and between neurons involves more than the mere circulation of stereotyped pulses. These impulses must be set up and generated by subthreshold processes. The differences between the firing behavior of most neurons and the squid giant axon reflect the roles of other voltage-dependent ionic conductances than the two described by Hodgkin and Huxley. Over the last two decades, more than several dozen membrane conductances have been characterized (Hagiwara, 1983; Llinás, 1988; Hille, 1992). They differ in principal carrier, voltage, and time dependence, dependence on the presence of intracellular calcium and on their susceptibility to modulation by synaptic inputs and second messengers. Our knowledge of these conductances and the role they play in impulse formation has accelerated rapidly in recent years as a result of various technical innovations such as single-cell isolation, patch clamping, and molecular techniques. We will here describe the most important of these conductances and briefly characterize each one. In order to understand more completely the functional role of these conductances in determining the response of the cell to input, empirical equations that approximate their behavior under physiological conditions must be developed and compared against the physiological preparations. In a remarkable testimony to the power and the generality of the Hodgkin-Huxley approach, the majority of such phenomenological models has used their methodology of describing individual ionic conductances in terms of activating and inactivating particles with first-order kinetics (see Chap. 6).