Long‐Term Effects of Neonatal Capsaicin Treatment on Intraepidermal Nerve Fibers and Keratinocyte Proliferation In Rat Glabrous Skin (original) (raw)
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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.
PLOS One, 2012
Background: The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing.
Neuroscience, 1988
AImDa&-The long-term effects of applying capsaicin briefly to a cutaneous nerve in the rabbit have been assessed 10 days after treatment. No changes in C-fibre numbers were seen in treated saphenous nerves and the average ratio of C-fibres to A-fibres was close to 7 in both control and treated nerves. However, the substance P content of the skin innervated by the saphenous nerve fell by 46% after capsaicin treatment compared with a fall of 65% after nerve section. Plasma extravasation in response to 7.5% mustard oil applied to the skin was also reduced following capsaicin treatment (by 43%) and following denervation (by 47%). although the response to 25% mustard oil was unaffected by previous capsaicin treatment. Thus, as in other species that have been examined (notably the rat), brief capsaicin treatment of rabbit skin nerves leads to a reduction in a neurogenic inflammatory response and in substance P content of the skin. However, unlike the rat, there is no degeneration of C-fibres. In the rabbit it is therefore possible to separate the neurotoxic, degenerative action of capsaicin from its ability to deplete substance P. The question of whether a similar dissociation between neurotoxic and other actions could be achieved in the rat by using lower capsaicin concentrations remains to be answered.
Experimental Dermatology, 2008
The peripheral nervous system comprises the autonomic and sensory (afferent) nervous systems. Major advances in our understanding of the autonomic and sensory transmission and function include the recognition of the phenotypic expression of a variety of transmitters and modulators that often coexist in individual neurons, the concept of co-transmission and chemical coding, the evidence for local effector functions of primary afferent nerves, and the discovery of plasticity of both the autonomic and the sensory nervous system during development, aging, diseases states, and inflammation. Co-transmission or plurichemical transmission, which indicates the release of more than one chemical messenger from the same neuron, enables autonomic and sensory neurons to exert a fine and highly regulated control of various functions such as circulation and immune response. The concept of chemical coding, in which the combination of transmitters/modulators is established, allows the identification of functional classes of neurons with their projections and targets. In addition to transmitters and modulators, autonomic and sensory neurons express multiple receptors, including G-proteincoupled and ion-gated receptors, further supporting the complexity of autonomic and sensory transmission and function. Autonomic neurons regulate the internal environment and maintain multiple homeostatic functions, and sensory neurons act as receptive structures that activate their targets in response to stimulation but also exert effector functions including the control of blood flow and vascular permeability, maintenance of mineralized tissue, and regulation of gene expression.
Journal of Dermatological Science, 2007
Background: Skin-scratching behavior, a common response observed in patients with pruritus, is supposed to promote the sprouting of cutaneous sensory nerve fibers. Thus, it sometimes exacerbates the original lesions. However, the precise changes that develop in cutaneous sensory nerve fibers after skin-scratching have not yet been elucidated. Objective: To investigate how and what kinds of cutaneous sensory nerve fibers increase and how nerve growth factor (NGF) and its receptors change after skinscratching. Methods: After scratching the dorsal skin of anesthetized ICR mice, change in cutaneous nerve fibers was detected by immunofluorescence for protein gene product 9.5 (PGP9.5), substance P (SP) and/or calcitonin gene-related peptide (CGRP). To investigate the involvement of NGF signaling, the production of NGF and the expression of its receptors were examined using ELISA and/or immunofluorescence, respectively. Results: Skin-scratching dramatically induced the sprouting of cutaneous nerve fibers. Both dermal and epidermal nerve fibers began to increase and reached a peak at days 3-7. At the same time, nerve fibers containing SP or CGRP increased significantly. NGF in the scratched skin increased immediately and reached a peak at days 1-3. The expression of NGF receptors, such as phosphorylated trk A and p75, on nerve fibers was remarkably upregulated within 2 days.
Clinical Neurophysiology, 2010
Capsaicin Skin biopsy Intra-epidermal nerve fibre density Laser-evoked potentials Quantitative sensory testing a b s t r a c t Objective: To assess the temporal relationship between skin nerve denervation and regeneration (dermal and intra-epidermal fibres, IENF) and functional changes (CO 2 laser-evoked potentials, LEPs, and quantitative sensory tests, QST) after topical cutaneous application of capsaicin. Methods: Capsaicin (0.075%) was applied to the lateral calf for three consecutive days. QST, LEPs and skin biopsies were performed at baseline and time intervals up to 54 days post-capsaicin treatment. Biopsies were immunostained with antibodies for PGP9.5, TRPV1, and GAP-43 (marker of regenerating nerve fibres), and analyzed for IENFs and dermal innervation (for GAP-43). Results: At 1 day post-capsaicin, cutaneous thermal sensitivity was reduced, as were LEPs. PGP9.5, TRPV1, and GAP-43 immunoreactive-nerve fibres were almost completely absent. By Day 12, LEPs had fully recovered, but PGP9.5 and TRPV1 IENF continued to be significantly decreased 54 days post-capsaicin. In contrast, dermal GAP-43 immunoreactivity closely matched recovery of LEPs. Conclusions: A good correlation was observed between LEPs and GAP-43 staining, in contrast to PGP9.5 and TRPV1. Laser stimulation is a non-invasive and sensitive method for assessing the initial IENF loss, and regenerating nerve fibres. Significance: Assessing skin biopsies by PGP9.5 immunostaining alone may miss significant diagnostic and prognostic information regarding regenerating nerve fibres, if other approaches are neglected, e.g. LEPs or GAP-43 immunostaining.
Experimental Dermatology, 2008
The peripheral nervous system comprises the autonomic and sensory (afferent) nervous systems. Major advances in our understanding of the autonomic and sensory transmission and function include the recognition of the phenotypic expression of a variety of transmitters and modulators that often coexist in individual neurons, the concept of co-transmission and chemical coding, the evidence for local effector functions of primary afferent nerves, and the discovery of plasticity of both the autonomic and the sensory nervous system during development, aging, diseases states, and inflammation. Co-transmission or plurichemical transmission, which indicates the release of more than one chemical messenger from the same neuron, enables autonomic and sensory neurons to exert a fine and highly regulated control of various functions such as circulation and immune response. The concept of chemical coding, in which the combination of transmitters/modulators is established, allows the identification of functional classes of neurons with their projections and targets. In addition to transmitters and modulators, autonomic and sensory neurons express multiple receptors, including G-proteincoupled and ion-gated receptors, further supporting the complexity of autonomic and sensory transmission and function. Autonomic neurons regulate the internal environment and maintain multiple homeostatic functions, and sensory neurons act as receptive structures that activate their targets in response to stimulation but also exert effector functions including the control of blood flow and vascular permeability, maintenance of mineralized tissue, and regulation of gene expression.