New neurophysiological findings on skin receptors or intradermal nerve endings after repetitive capsaicin application (original) (raw)
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Neurogenic flare responses following topical application of capsaicin in humans
Annals of Neurology, 1985
The flare response to noxious stimulation of the skin is mediated by polymodal nociceptors of C fiber primary afferent nerves. Topical application of capsaicin initiates a flare response and burning pain. In this study, the variability of capsaicin-induced flare and pain was assessed in 220 subjects. The major factors in flare response are body site and age; more severe reactions occur in more proximal sites and in younger subjects. Larger flares were shown to be associated with greater pain. Variability is probably due to differences in the structure and reactivity of the neurovascular unit as proposed in the Lewis model of the axon reflex. It may prove possible to assess polymodal nociceptor function using topical capsaicin in disease states that affect the peripheral terminals of primary afferent nerves.
Somesthetic and electrophysiologic effects of topical 0.025% capsaicin in man
Regional anesthesia, 1990
As a topical agent, capsaicin reportedly blocks pain without otherwise impairing sensation. Ten subjects underwent blinded, multiple-dose application of topical 0.025% capsaicin or control emollient to skin test sites in order to evaluate capsaicin effectiveness and toxicity. Clinical changes in somesthetic perception of pinprick, heat and cold developed, but neurogenic flare responses were unchanged. Clinical and electrophysiologic measures of large fiber and autonomic function were unaffected by capsaicin. This study indicates that 0.025% capsaicin is a safe topical agent with demonstrable clinical effects on small fiber function but not on large fiber or autonomic function.
The Journal of Neuroscience, 1998
The ability of capsaicin to excite and subsequently to desensitize a select group of small sensory neurons has made it a useful tool to study their function. For this reason, application of capsaicin to the skin has been used for a variety of painful syndromes. We examined whether intradermal injection of capsaicin produced morphological changes in cutaneous nerve fibers that would account for its analgesic properties by comparing cutaneous innervation in capsaicin-treated skin with psychophysical measures of sensation. At various times after capsaicin injection, nerve fibers were visualized immunohistochemically in skin biopsies and were quantified. In normal skin the epidermis is heavily innervated by nerve fibers immunoreactive for protein gene product (PGP) 9.5, whereas fibers immunoreactive for substance P (SP) and calcitonin gene-related peptide (CGRP) are typically associated with blood vessels. There was nearly complete degeneration of epidermal nerve fibers and the subepide...
Experimental Dermatology, 2014
Using an ex vivo skin-nerve preparation, skin and nerve cells were reconstituted into a single unit and maintained in a nutrient medium bath until required experimentally. Our objective was to use the epidermis as a relay for the induction of an electric current to the neurons following the topical application of capsaicin on the skin epidermis of the skin explant, an agonist of the TRPV1 channel implicated in pruritus and pain. After 10-20 days of coculture to form the re-innervated skin model, we applied a solution of capsaicin directly on the epidermis of the skin explant (4 lM). The resulting current was recorded using a path-clamp technique on the neuronal fibres. Following the topical application of capsaicin, spontaneous activity was triggered, as characterised by repetitive spikes with periods of 125, 225 or 275 ms. This study demonstrates that the skin explant and nerve cells preparation may receive stimuli and be used to screen molecules or to study signal transmission.
Brain, 2000
Burning pain was induced in healthy human subjects by of mechano-responsive C-units was too short to account for the duration of the burning pain. The latter generally intracutaneous injections of capsaicin (20 µl, 0.1%) in the innervation territory of the cutaneous branch of the were desensitized to mechanical stimulation at the injection site, whereas 8 of 17 of the originally mechano-peroneal nerve and the pain responses were compared with the activation patterns of afferent C-fibres recorded insensitive C-units became responsive to mechanical probing at the injection site after capsaicin. Responses by microneurography. Responsiveness of single units to mechanical or heat stimuli or to sympathetic reflex typically started several seconds after the onset of the mechanical stimulus in parallel with pain sensations. We provocation tests was determined by transient slowing of conduction velocity following activation (marking did not observe sensitization to brushing or to punctate stimuli in uninjured parts of the innervation territory. technique). Capsaicin activated each of 12 mechanoresponsive and 17 of 20 mechano-insensitive C-units. Differential capsaicin sensitivity adds to the cumulating evidence for the existence of two categories of functionally However, the duration of the responses to capsaicin was significantly longer in mechano-insensitive C-units different nociceptors in human skin, with a special role for mechano-insensitive fibres in sensitization and (median 170 s; quartiles 80-390) compared with mechanoresponsive C-units (8 s; 4-10). The activation times of hyperalgesia. Possible structural differences between these two categories are discussed, including the role of mechano-insensitive C-units closely matched the duration of capsaicin-induced pain responses, whereas activation tetrodotoxin-resistant sodium channels.
The effect of topical capsaicin-induced sensitization on heat-evoked cutaneous vasomotor responses
International journal of physiology, pathophysiology and pharmacology, 2013
Brief, localized, cutaneous, non-painful thermal stimuli can evoke a transient vasomotor response, causing increased cutaneous blood flow and elevated skin temperature. The aims of this study were to investigate 1) if cutaneous sensitization by topical application of capsaicin (TRPV1 receptor agonist) can facilitate the size, duration and spatial extent of this vasomotor response and 2) if males and females respond differently. Thermal pulses (43°C for 60 seconds) were applied on left/right volar forearms of 15 age-matched males and females. Skin temperature and cutaneous blood flow were measured 1, 5, 10, 15, and 30 minutes after heat application before and after topical capsaicin (1%, 30 min application) with contralateral arm serving as the control. Recordings were made from the region of interest at distances of 2, 4, 6, 8, and 10 cm from the capsaicin application site. Sensitization significantly enhanced skin temperature for up to 30 min and compared with non-sensitized skin a...
Capsaicin-sensitive cutaneous primary afferents convey electrically induced itch in humans
Neuroscience Letters, 2018
Specially designed transcutaneous electrical stimulation paradigms can be used to provoke experimental itch. However, it is unclear which primary afferent fibers are activated and whether they represent pathophysiologically relevant, C-fiber mediated itch. Since low-threshold mechano-receptors have recently been implicated in pruriception we aimed to characterize the peripheral primary afferent subpopulation conveying electrically evoked itch in humans (50 Hz stimulation, 100 μs square pulses, stimulus-response function to graded stimulus intensity). In 10 healthy volunteers a placebo-controlled, 24-hour, 8% topical capsaicin-induced defunctionalization of capsaicinsensitive (transient receptor potential V1-positive, 'TRPV1 +') cutaneous fibers was performed. Histaminergic itch (1% solution introduced by a skin prick test lancet) was provoked as a positive control condition. Profound losses of warmth and heat pain sensitivity (pain threshold and supra-threshold ratings) as assessed by quantitative sensory testing, were found as indicative for efficient TRPV1-fiber defunctionalization (all outcomes: P <0.0001). The topical capsaicin profoundly, and with equal efficaciousness, inhibited itch intensity evoked by electrical stimulation and histamine (-89 ± 4.1% and-78% ±4.9%, respectively, both: P <0.0001 compared to the placebo patch area). The predominant primary afferent substrate for electrically evoked itch in humans, using the presently applied stimulation paradigm, is concluded to be capsaicin-sensitive polymodal C-fibers.
Real-Time Investigation of Skin Blood Flow Changes Induced by Topical Capsaicin
2017
Capsaicin induces a localized inflammatory process known as neurogenic inflammation upon its topical administration on the skin, due to the release of various neuropeptides from the cutaneous sensory nerve endings. In this study, we investigated real-time skin blood flow changes that occur in neurogenic inflammation induced by topical capsaicin by means of in vivo reflectance confocal microscopy. 27 healthy subjects (15 women and 12 men, mean age ± Standard Deviation: 22.62±4.47) were administered topical capsaicin solution (Capsaicin group) or immersion oil (Control group) on the dorsal side of their non-dominant hand. At different time intervals during administration (0, 10, 25, and 40 minutes), cutaneous blood flow was evaluated using reflectance confocal microscopy and compared between the two groups. Blood flow values were higher during topical capsaicin, with significant increase after 25 (P=0.0160, Dunn's multiple comparisons test) and 40 minutes (P=0.0132, Dunn's mul...