Vasodilatation in human skin induced by low-amplitude high-frequency vibration

Summary. Vasomotor effects in human skin induced by vibration of low amplitude (10–25 μm) and high frequency (150–250 Hz) have been studied by using skin temperature changes as an approximative measure of variations in skin blood flow. In all tested areas of the body surface, including the face, low-amplitude high-frequency vibration regularly induces vasodilatation. The spatial distribution of the temperature changes induced from different sites of stimulation was studied by infrared thermography. The latencies of the temperature changes, determined by thermistor recordings, were found to vary with site of stimulation and stimulus parameters. The increase in temperature to a given stimulus is greater the lower the prevalent skin temperature, i.e. the increase in blood flow is larger the greater the initial vasomotor tone. The results are in accordance with the view that the vasodilatation is due to a reflex inhibition of pre-existent vasomotor tone in the skin by the afferent inflow from vibration-sensitive mechanoreceptors. High-amplitude vibration (100–200 μm), performed in a few comparative experiments, caused vasoconstriction.     

Sympathetic skin response following painful electrical stimulation is increased in major depression

Patients with major depressive disorder have repeatedly been described to exhibit increased thresholds upon experimentally applied pain stimuli to the skin as compared to respective controls. Since the sensory-discriminative component of stimulus perception, e.g. for warmth, cold and vibration, appears to be unaltered in depression, higher central nervous centres have been assumed to cause this phenomenon. To date, hardly any attention has been paid to the efferent components of the noxious reflex loop. Here, we aimed to assess the autonomic reaction upon a painful stimulus and to examine whether this is likewise reduced in major depression. For this purpose, sympathetic skin response was obtained from 22 patients with major depression and 20 matched controls. To induce sympathetic skin responses, we applied either noxious electrical stimuli (12 and 18 mA) or innocuous acoustic stimuli (85 dB SPL). Pain intensity was rated using a numeric analogue scale. In contrast to our a priori hypothesis patients showed shorter latencies and higher amplitudes of skin potentials upon noxious stimulation, i.e. a stronger sympathetic response. Intriguingly, the noxious stimuli were still perceived less painful in the patient group. Pain perception weakly correlated with disease severity. From these data, we conclude that despite the diminished pain perception, the autonomic reflex loop following noxious stimulation is not affected in patients with major depressive disorder, and that the increase in sympathetic outflow is not directly related to the perceived pain as in controls, but might rather be attributed to the autonomic dysfunction known for the disease.     

The influence of ulnar nerve blockade on skin microvascular blood flow*

Abstract. Microvascular research is seriously hampered by the great temporal and spatial variability of the measured skin blood flow and variation in sympathetic vasomotor reflexes within and between persons. Therefore skin vasomotor reflexes were studied before and after ulnar nerve blockade within the same person, resulting in a temporal complete denervation of the fifth finger and partial denervation of the fourth finger. Skin temperature and laser Doppler flux (LDF) were registrated to measure predominantly arteriove-nous shuntflow. Measurements were performed on the palmar tip of the second and fifth finger in nine healthy volunteers, at baseline, and during a sympathetic reflex test (i.e. inspiratory gasp) and postural response test. Beat-to-beat digital blood pressure was recorded from the third and fourth finger by a Finapres device. Baseline capillary blood cell velocity (CBV) was measured at the nailfold of the second and the fifth finger. After ulnar blockade baseline skin temperature, LDF and CBV increased significantly, with respectively (mean±SE) 3.2±0.9d?C, 20.9 ±5.9 relative perfusion units and 0.79 ±0.40 mm^-1 s. The percentage LDF decrease of the fifth finger during inspiratory gasp was 48.2 ±5.3% before and 31 ±0.9% after blockade. The postural response test showed a decrease in LDF of the fifth finger with no significant difference before and after blockade, respectively 12.3± 14.7% and 8.0±2.7%, while no difference was found in the increase in digital blood pressure in the denervated fourth finger compared to both the same finger before blockade and to the third non-blocked finger. It is concluded that ulnar nerve blockade enables the study of sympathetic skin vasomotor reflexes by comparison of a denervated and a non-denervated vascular bed within the same person. After ulnar blockade arteriovenous shunt flow as well as nutritional capillary blood flow increased significantly. Postural vasoconstrictor response is not abolished by ulnar blockade, suggesting that local regulatory mechanisms are more important.     

皮肤与内脏相关的神经基础研究

目的在皮内注药治疗遗尿症及内脏痛有效的基础上,研究皮肤与内脏相关的初级神经元和交感神经元分布规律。方法通过家兔静脉注射伊文氏蓝(EvansBlue),胃内注入甲醛致胃伤害性刺激,观察皮肤渗漏斑,找出皮肤牵涉区;在牵涉区皮肤和胃黏膜分别注射辣根过氧化物酶(HRP)和荧光素核黄(NY)用神经逆行追踪法分别观察初级神经元和交感神经元分布规律。结果家兔胃痛的皮肤牵涉区在肩及肩胛区,在牵涉区皮肤和胃黏膜分别注射HRP和NY在C8～T8脊神经节和交感神经节相互重叠。结论胃痛的皮肤牵涉区与胃黏膜初级神经元分布的特点是在脊神经节呈节段性分布且相互重叠,在交感神经节呈弥散性分布,无节段性分布,也相互重叠,这可能是皮内注药治疗内脏痛的神经基础。     

Computer-assisted infrared thermographic study of axon reflex induced by intradermal melittin

The aim of the present study was to investigate whether melittin, the principal toxin of the honeybee (Apis mellifera) venom, can be used as an algogenic agent in the study of pain in humans. Five micrograms of melittin in 0.5 ml of saline was intradermally injected into the volar aspect of the forearm. Resultant pain was scored by a visual analogue scale (VAS), and skin temperature change was analyzed by means of a computer-assisted infrared thermography. Intradermal melittin temporarily produced severe pain, followed by a sustained increase in skin temperature. The skin temperature increase peaked in about 10 min and outlasted 1 h. Topical application of 10% lidocaine gel did not significantly suppress the melittin-induced pain, but markedly suppressed both the increase in the peak temperature and the area of temperature increase. In conclusion, 5 microg of melittin is sufficient to produce pain in humans and 10% lidocaine gel differentially decreases the melittin-induced axon reflex without any significant analgesic effect.     

Laser Doppler measurements of skin blood flow before,during, and after lumbar sympathetic blockade in children and young adults with reflex sympathetic dystrophy syndrome

Changes in the skin capillary blood flow (SBF) and temperature before, during, and 1 hour after unilateral lumbar paravertebral sympathetic blockade (LSB) were studied simultaneously with laser Doppler flowmetry and thermometry in patients with reflex sympathetic dystrophy syndrome. The baseline flow measurements in the toes on the affected limb were significantly lower than in the contralateral limb (p<0.01). During LSB, a 10-fold increase in SBF was detected within 4 minutes after injection of a local anesthetic agent when the sympathetic blockade was effective; an increase of more than 1°C in the skin temperature occurred within 11 minutes. Measurements 1 hour after blockade showed an 18-fold (mean) increase in SBF in the toes (p<0.0001) and a 2-fold (mean) increase in SBF in the thighs (p<0.001). There was a significant decrease in the skin blood flow in the contralateral toes after the sympathetic blockade (p<0.01). We conclude that laser Doppler flow measurements can be used to detect immediate onset of sympathetic blockade in patients under general anesthetic or conscious sedation.     

Regional intravenous guanethidine vs. stellate ganglion block in reflex sympathetic dystrophies: a randomized trial

Regional intravenous guanethidine blocks and stellate ganglion blocks have been compared in a randomized trial. Nineteen patients, randomly allocated to two groups of therapy and exhibiting severe reflex sympathetic dystrophy following peripheral nerve lesions, have been treated. The performance of the intravenous guanethidine block is of longer duration and superior to stellate ganglion block, as regards some early pharmacological effects (skin temperatures and amplitude of plethysmographic waves recorded before blockade and 15 min, 60 min, 24 h, 48 h after institution of the block). In fact the intravenous guanethidine group shows a persistent and significant increase of the skin temperature and of the plethysmographic traces in the blocked side 24 h and 48 h after blockade in comparison with the patients treated with stellate ganglion block. Concerning the therapeutic effects (changes in pain scores and clinical signs--hyperpathia, allodynia, vasomotor disturbances, trophic changes, oedema and limited motion), recorded at the end of treatment and 1 month and 3 months follow-up, an intravenous guanethidine block carried out every 4 days up to a total of 4 blocks is comparable with a stellate ganglion block every day up to a total of 8 blocks. The results of this study show that regional sympathetic block with guanethidine is a good therapeutic tool in the treatment of reflex dystrophies, especially on account of its negligible risks and contraindications.     

An association between phantom limb sensations and stump skin conductance during transcutaneous electrical nerve stimulation (TENS) applied to the contralateral leg: a case study

This report describes a placebo-controlled study of transcutaneous electrical nerve stimulation (TENS) applied to the contralateral lower leg and outer ears of an amputee with non-painful phantom sensations. The subject received TENS or placebo stimulation on separate sessions in which baseline periods of no stimulation alternated with periods of TENS (or placebo). Throughout the two sessions, continuous measures of stump skin conductance, surface skin temperature and phantom intensity were obtained. The results showed that TENS applied to the contralateral leg was significantly more effective than a placebo in decreasing the intensity of phantom sensations, whereas stimulation of the outer ears led to a non-significant increase. The pattern of electrodermal activity on the TENS session was consistently linear during baseline periods, indicating a progressive increase in sympathetic sudomotor activity. In contrast, during periods of electrical stimulation the pattern of electrodermal activity was consistently curvilinear indicating an initial decrease followed by an increase in sudomotor responses. Changes in stump skin conductance correlated significantly with changes in phantom sensations both in TENS and placebo sessions suggesting a relationship between sympathetic activity at the stump and paresthesias referred to the phantom. Two hypotheses are presented to account for these findings.     

Sudomotor and vasomotor activity during the menstrual cycle with global heating

Many studies have reported that there are changes in sympathetic activity throughout the menstrual cycle as there are oestrogen receptor in the hypothalamus and all other parts of the sympathetic nervous system. The purpose of this study was to see whether there were variations in sympathetic activity, skin vasomotor and sweat gland sudomotor rhythms during the menstrual cycle. Eight young female subjects with a regular menstrual cycle participated in the study. Subjects were tested once during the follicular phase and once during the luteal phase. Skin blood flow and sweat rate were significantly higher in the luteal phase compared with the follicular phase (p < .05), but the frequency and magnitude of sudomotor and vasomotor rhythms were significantly greater in the follicular phase (p < .05). In contrast, spectral data showed less sympathetic activity in the luteal phase. A significant finding here is that the sudomotor rhythm of sweat glands is altered by the menstrual cycle.     

High prevalence of vasomotor reflex impairment in newly diagnosed leprosy patients

BACKGROUND: Initial nerve damage in leprosy occurs in small myelinated and unmyelinated nerve fibers. Early detection of leprosy in the peripheral nervous system is challenging as extensive nerve damage may take place before clinical signs of leprosy become apparent. PATIENTS AND METHODS: In order to determine the prevalence of, and factors associated with, peripheral autonomic nerve dysfunction in newly diagnosed leprosy patients, 76 Brazilian patients were evaluated prior to treatment. Skin vasomotor reflex was tested by means of laser Doppler velocimetry. Blood perfusion and reflex vasoconstriction following an inspiratory gasp were registered on the second and fifth fingers. RESULTS: Vasomotor reflex was impaired in at least one finger in 33/76 (43%) patients. The fifth fingers were more frequently impaired and suffered more frequent bilateral alterations than the second fingers. Multivariate regression analysis showed that leprosy reaction (adjusted odds ratio = 8.11, 95% confidence interval: 1.4-48.2) was associated with overall impaired vasomotor reflex (average of the four fingers). In addition, palmar erythrocyanosis and an abnormal upper limb sensory score were associated with vasomotor reflex impairment in the second fingers, whereas anti-phenolic glycolipid-I antibodies, ulnar somatic neuropathy and a low finger skin temperature were associated with impairment in the fifth fingers. CONCLUSIONS: A high prevalence of peripheral autonomic dysfunction as measured by laser Doppler velocimetry was observed in newly diagnosed leprosy patients, which is clinically evident late in the disease. Autonomic nerve lesion was more frequent than somatic lesions and was strongly related to the immune-inflammatory reaction against M. leprae.     

Effect of burst-mode transcutaneous electrical nerve stimulation on peripheral vascular resistance

BACKGROUND AND PURPOSE: Based on changes in skin temperature alone, some authors have proposed that postganglionic sympathetic vasoconstrictor fibers can be stimulated transcutaneously. Our goal was to determine the effects of low-frequency (2 bursts per second), burst-mode transcutaneous electrical nerve stimulation (TENS) on calf vascular resistance, a more direct marker of sympathetic vasoconstrictor outflow than skin temperature, in subjects with no known pathology. SUBJECTS: Fourteen women and 6 men (mean age=31 years, SD=13, range=18-58) participated in this study. METHODS: Calf blood flow, arterial pressure, and skin temperature were measured while TENS was applied over the common peroneal and tibial nerves. RESULTS: Blood flow immediately following stimulation was not affected by TENS applied just under or just above the threshold for muscle contraction. Transcutaneous electrical nerve stimulation applied at 25% above the motor threshold caused a transient increase in calf blood flow. Regardless of stimulation intensity, TENS had no effect on arterial pressure; therefore, calf vascular resistance decreased only during the trial that was 25% above the motor threshold. Regardless of stimulation intensity, TENS failed to alter dorsal or plantar skin temperature. DISCUSSION AND CONCLUSION: These results demonstrate that the effects of TENS on circulation depend on stimulation intensity. When the intensity was sufficient to cause a moderate muscle contraction, a transient, local increase in blood flow occurred. Cooling of the dorsal and plantar skin occurred in both the stimulated and control legs, most likely because skin temperature acclimatized to ambient room temperature, rather than because of any effect of TENS on circulation. The data, therefore, call into question the idea that postganglionic sympathetic efferent fibers are stimulated when TENS is applied at clinically relevant intensities to people without symptoms of cardiovascular or neuromuscular pathology.     

The effects of chiropractic adjustments on distal skin temperature

Stimulation of the sympathetic nervous system will cause a reduction in the skin blood flow which can be detected by measuring the skin surface temperature. The purpose of this study was to see whether chiropractic adjustments could affect the activity of the sympathetic nervous system as reflected by changes in distal (fingertip) skin temperature. Skin temperature on 196 subjects was measured before and within 10 sec after a spinal adjustment. The difference between the pre- and post-temperatures was determined. The average fingertip temperature did not change when the spine was considered as an entire unit. However, when sympathetic and nonsympathetic regions were analyzed separately, we found significant differences in temperature response. The average temperature rose from 85.84 +/- 6.04 degrees F to 86.26 +/- 6.25 degrees F when C1-C7 and/or L4-L5 were adjusted (p less than 0.001). When the area between T1-L3 was adjusted, however, the average temperature fell from 84.97 +/- 6.11 degrees F to 84.72 +/- 6.19 degrees F (p less than 0.001). These results illustrate that the blood flow through the fingertips can be affected by specific adjustments to the spine, and, further, that the response varies, depending on the location of the adjustment. Thus, adjustments to the spine can, via stimulation of the nervous system, affect the physiology of tissues distant from the spine.     

Parametric and pharmacological studies of midbrain suppression of the hind limb flexion withdrawal reflex in the rat

These experiments quantitatively analyzed effects of electrical midbrain stimulation on a nociceptive hind limb flexion reflex in rats anesthetized with sodium pentobarbital. We recorded the force of isometric hind limb flexion withdrawal, and related flexor electromyographic (EMG) activity, elicited by noxious heat (42-54 degrees C, 10 sec) applied to the ventral hind paw. Several hind limb flexors including biceps femoris were active during the reflex. Quantified reflex responses to identical noxious heat stimuli delivered every 2 min were constant in magnitude and were reduced or abolished during stimulation (100 msec trains at 100 Hz, 3/sec, 15-325 microA) in the midbrain periaqueductal gray (PAG) or lateral reticular formation (LRF). LRF was significantly more effective than PAG stimulation in suppressing reflex responses. The magnitude of the reflex responses increased with graded increases in the temperature of the noxious heat stimulus. The slope of the temperature-response relationship was significantly reduced during PAG stimulation, whereas it was shifted toward higher temperatures with significantly increased threshold during LRF stimulation. To investigate possible transmitters involved, we tested if PAG- or LRF-evoked reflex suppression was affected following systemic administration of the opiate antagonist naloxone, the serotonin antagonist methysergide, the noradrenergic antagonist phentolamine, or the cholinergic antagonist scopolamine. Naloxone had little effect, while methysergide and phentolamine reduced PAG- and LRF-evoked reflex suppression in about one-half of the cases. Scopolamine largely reduced PAG- and LRF-evoked reflex suppression (in 8/9 and 4/6 rats, respectively). These results indicate that the flexion reflex is under parametrically but not pharmacologically distinct inhibitory midbrain controls.     

Neurophysiological assessment of spinal cord stimulation in failed back surgery syndrome

Despite good clinical results, the mechanisms of action of spinal cord stimulation (SCS) for the treatment of chronic refractory neuropathic pain have not yet been elucidated. In the present study, the effects of SCS were assessed on various neurophysiological parameters in a series of 20 patients, successfully treated by SCS for mostly unilateral, drug-resistant lower limb pain due to failed back surgery syndrome. Plantar sympathetic skin response (SSR), F-wave and somatosensory-evoked potentials (P40-SEP) to tibial nerve stimulation, H-reflex of soleus muscle, and nociceptive flexion (RIII) reflex to sural nerve stimulation were recorded at the painful lower limb. The study included two recording sets while SCS was switched ‘ON’ or ‘OFF’ for 1 h. Significant changes in ‘ON’ condition were as follows: SSR amplitude, H-reflex threshold, and RIII-reflex threshold and latency were increased, whereas SSR latency, F-wave latency, H-reflex amplitude, P40-SEP amplitude, and RIII-reflex area were reduced. Analgesia induced by SCS mainly correlated with RIII attenuation, supporting a real analgesic efficacy of the procedure. This study showed that SCS is able to inhibit both nociceptive (RIII-reflex) and non-nociceptive (P40-SEP, H-reflex) myelinated sensory afferents at segmental spinal or supraspinal level, and to increase cholinergic sympathetic skin activities (SSR facilitation). Complex modulating effects can be produced by SCS on various neural circuits, including a broad inhibition of both noxious and innocuous sensory information processing.     

Effects of Slump Long Sitting on Peripheral Sudomotor and Vasomotor Function: A Pilot Study

Abstract

Slump long sitting combined with spinal lateral flexion and costovertebral joint mobilization, or “slump long sitting with sympathetic emphasis” (SLSSE), is purported to be an effective therapeutic technique for the management of sympathetically maintained pain. It is hypothesized that the SLSSE would facilitate a sympathoexcitatory response resulting in an increase in skin conductivity and a decrease in skin temperature. However, the impact of SLSSE on sympathetic activity is poorly understood, and there is no direct evidence that the SLSSE affects sympathetic activity in the lower extremities. The purpose of this study was to assess sympathetically-mediated peripheral sudomotor (sweating) and vasomotor (temperature) activity in the feet of healthy, asymptomatic individuals during SLSSE and long sitting. A convenience sample of 12 healthy young adults was split randomly into control and experimental groups of equal size. Sudomotor and vasomotor activities were quantified during SLSSE (experimental group) and long sitting (control group). Although sample mean skin temperature and conductance changes relative to baseline measurements were greater in the experimental group (-2.14% temperature, 51.0% conductivity) than in the control group (-1.425% temperature, 35.8% conductivity), a two-way mixed ANOVA, with side of body as the within-subject factor, indicated no main effects. Nevertheless, trends in these data – one of which would likely have been supported statistically with a slightly larger sample size - should be encouraging to manual therapists and researchers.     

Skin microvascular circulation in the sympathetic dystrophies evaluated by videophotometric capillaroscopy and laser Doppler fluxmetry

Finger-skin microcirculation and its reactions to sympathetic stimuli were investigated in 12 patients with sympathetic dystrophies, secondary to trauma or other diseases. Nailfold-skin capillary blood cell velocity (CBV) was measured by videophotometric capillaroscopy. Laser Doppler fluxmetry was used to provide an index of skin circulation in vessels in addition to the superficial capillaries. Both CBV and laser Doppler flux (LDF) values were significantly lower in the patients, compared with the healthy controls (P less than 0.05), despite the fact that skin temperature was the same in both groups. During cooling of the contralateral hand, CBV and LDF decreased markedly (22-60%) in the control group but not in the patients (0-13%). The decrease in skin perfusion normally seen upon lowering of the hand was also impaired in the patient group (7%) compared with controls (42%) (P less than 0.05). These impaired vasomotor reflex responses are consistent with sympathetic dysfunction and may well explain some of the typical features of the syndrome, e.g. limb oedema.     

Local sympathetic reflex control of blood flow in human skin following topical corticosteroid treatment

Local positional vasomotor activity, or the veno-arteriolar reflex, was studied in normal human skin over 3 days of treatment with a potent corticosteroid under occlusion. Eight healthy subjects participated in the study. Using the atraumatic epicutaneous 133-Xe washout technique on the outer 2 mm of the skin fold between the first and the second finger, and covering the rest of the hand with a lead shield, blood flow in cutaneous tissue only was monitored. The veno-arteriolar reflex was elicited by inducing venous stasis. Before treatment, 40 mmHg venous stasis reduced cutaneous blood flow by 37.1% (95 percentile, 24.5-56.0). Following 24 h and 48 h of treatment, the reflex became weaker and at day 3, the blood flow reduction was 17.8% (7.6-42.6). The diminution was significant (p less than 0.05).     

Changes in plasma catecholamines in response to reflex modulation of sympathetic vasoconstrictor tone by cardiopulmonary receptors

The effects of selective deactivation and stimulation of cardiopulmonary receptors on plasma noradrenaline (radioenzymatic method) were studied in nine normotensive subjects by reducing and increasing central venous pressure for 20 min via lower body suction and leg-raising manoeuvres that did not alter arterial blood pressure and heart rate. Deactivation of cardiopulmonary receptors was accompanied by a rise in plasma noradrenaline that achieved a peak within 5 min (91.8 +/- 22%, mean +/- SE) and was then sustained. Stimulation of cardiopulmonary receptors was accompanied by a fall in plasma noradrenaline (-16.6 +/- 3.4%) that levelled off at the second minute and was then sustained. On average the increase and the reduction in plasma noradrenaline had a time course and a magnitude similar to the increase (80.5 +/- 10.5%) and the reduction (-28.4 +/- 5%) in forearm vascular resistance (derived from plethysmographic flow measurement) concomitantly caused by cardiopulmonary receptors. Furthermore, analysis of individual data showed that changes in plasma noradrenaline and forearm vascular resistance were linked by a positive relationship (r = 0.64). Thus the cardiopulmonary receptor reflex can produce rapid, marked and sustained changes in both plasma noradrenaline and forearm vasomotor tone. This is in sharp contrast with the previously observed inability of the carotid baroreflex to alter both these humoral and haemodynamic variables. Taken together these findings support the hypothesis that sympathetic tone to skeletal muscle is an important determinant of the concentration of plasma noradrenaline in blood.     

Heat-induced release of CGRP from isolated rat skin and effects of bradykinin and the protein kinase C activator PMA.

In the skin, noxious heating induces an axon reflex response which is commonly accepted to be due to the release of vasodilatory neuropeptides from polymodal nociceptors. In the present study, the quantitative assessment of calcitonin gene-related peptide (CGRP) release from rat skin serves as an integrative measure of primary afferent activation by noxious heat and the presumed sensitising action of bradykinin and an activator of protein kinase C (PKC). The isolated rat hairy skin of either hind paw was mounted on acrylic rods and exposed for 5 min periods to synthetic interstitial fluid of either 32 degrees C for control or of higher temperatures up to 59 degrees C during stimulation. In addition, experiments were performed in calcium free solution (containing 10 mM EGTA) or the skin was preloaded with the membrane permeant calcium chelator BAPTA-AM (1 mM). To look for modulatory effects on the heat responses, bradykinin or polymyristate-acetate (PMA) were added during heat stimulation in further experiments. Heating the skin induced a temperature-dependent release of CGRP from a threshold of 43 degrees C which was absent in calcium free solution. Only at the highest temperatures (55 and 59 degrees C) was a partially calcium-independent release observed. Inhibition of the release was also obtained with the intracellular calcium buffer BAPTA-AM. Bradykinin 10 but not 1 microM as well as PMA 1 and 10 microM significantly facilitated the heat-induced CGRP release at 47 degrees C whereby BK caused a marginal and PMA a significant CGRP release by itself. Our results indicate that moderate noxious heat induces calcium-dependent CGRP release and this can be facilitated by bradykinin and by the activation of PKC. This suggests the same sensitising mechanism that affects nociceptor heat responses.     

Secondary hyperalgesia persists in capsaicin desensitized skin

Several lines of evidence suggest that secondary hyperalgesia to punctate mechanical stimuli arises from central sensitization to the input from primary afferent nociceptors. Conventional C-fiber nociceptors respond to heat stimuli and yet heat hyperalgesia is absent in the region of secondary hyperalgesia. This evidence suggests that the central sensitization to nociceptor input does not involve heat sensitive nociceptors. To test this hypothesis, we investigated whether desensitization of heat sensitive nociceptors by topical application of capsaicin led to an alteration in the secondary hyperalgesia. Two 2x2 cm areas on the volar forearm, separated by 1 cm, were treated in 10 healthy volunteers. One of the areas was desensitized by treatment with 10% topical capsaicin (6 h/day for 2 days). The other site served as vehicle control. Hyperalgesia was produced 2 days later by an intradermal injection of capsaicin (50 microg, 10 microl) at a point midway between the two treatment areas. Secondary hyperalgesia to noxious mechanical stimuli was investigated by using a blade probe (32 and 64 g) attached to a computer-controlled mechanical stimulator. In the area of topical capsaicin treatment, there was a marked increase in heat pain threshold and decrease in heat pain ratings indicating a pronounced desensitization of heat sensitive nociceptors. However, touch threshold and pain to pinching stimuli were not significantly altered. The intradermal capsaicin injection led to the development of a similar degree of secondary hyperalgesia at both the vehicle and capsaicin treatment areas. These results indicate that capsaicin insensitive nociceptive afferents play a dominant role not only in normal mechanical pain but also in secondary hyperalgesia to noxious mechanical stimuli.