Capsaicin, Nociception and Pain (original) (raw)
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Neuropharmacology, 2003
Capsiate is a capsaicin-like ingredient of a non-pungent cultivar of red pepper, CH-19 sweet. To elucidate the mechanisms underlying the non-pungency of capsiate, we investigated whether capsiate activates the cloned capsaicin receptor, TRPV1 (VR1). In patch-clamp experiments, capsiate was found to activate TRPV1 expressed transiently in HEK293 cells with a similar potency as capsaicin. Capsiate induced nociceptive responses in mice when injected subcutaneously into their hindpaws with a similar dose dependency as capsaicin. These data indicate that the non-pungent capsiate is an agonist for TRPV1 and could excite peripheral nociceptors. In contrast to this, capsiate did not induce any significant responses when applied to the skin surface, eye or oral cavity of mice, suggesting that capsiate requires direct access to nerve endings to exhibit its effects. Capsiate was proved to have high lipophilicity and to be easily broken down in normal aqueous conditions, leading to less accessibility to nociceptors. Another highly lipophilic capsaicin analogue, olvanil, was similar to capsiate in that it did not produce irritant responses when applied to the skin surface, although it could activate TRPV1. Taken together, high lipophilicity and instability might be critical determinants for pungency and so help in understanding the effects of capsaicin-related compounds.
2000
Capsaicin, the active ingredient in hot chilli peppers, has selective actions on unmyelinated C-fibres and thinly myelinated A primary sensory neurones . Most capsaicin-sensitive fibres are polymodal nociceptors which respond to a range of sensory stimuli including noxious pressure, heat and chemical irritants , and are the most abundant class of nociceptive fibre. Nociceptive neurones are likely to release glutamate as a rapid central neurotransmitter, and also express neuropeptides such as calcitonin gene-related peptide (CGRP), substance P, neurokinin A and somatostatin which can be released into the spinal cord during intense stimulation . The tachykinins (e.g. substance P and neurokinin A) and excitatory amino acids (EAAs) (e.g. glutamate) cooperate and are thought to increase synaptic activation of dorsal horn neurones via EAA receptors . Noxious stimulation in the peripheral nervous system results in long-term increases in spinal excitability which may contribute to central mechanisms of allodynia and hyperalgesia . Much of the neuropeptide synthesized in the dorsal root ganglion (DRG) cell body is actually exported peripherally rather than centrally. In peripheral nerve peptide release can contribute to neurogenic inflammation.
The Capsaicin Paradox: Pain Relief by an Algesic Agent
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 2011
Chemosensitive primary sensory neurones expressing the TRPV1 receptor, a molecular integrator of diverse noxious stimuli, play a fundamental role in the sensation of pain. Capsaicin, the archetypical ligand of the TRPV1 receptor, is one of the most painful chemical irritants, and its acute administration onto the skin and mucous membranes elicits severe pain. However, repeated or high-dose applications of capsaicin, and/or its administration through specific routes dramatically decreases the sensitivity of the innervated tissues to noxious chemical and heat stimuli. This review surveys the mechanisms of the antinociceptive, anti-inflammatory and anti-hyperalgesic effects of vanilloid agonists applied topically, or perineurally, or injected into the subarachnoid space in animal experiments and to put these data into a clinical perspective. The great body of available experimental evidence indicates that vanilloid agonists exert their antinociceptive actions through TRPV1 receptor-mediated selective neurotoxic/neurodegenerative effects directed against somatic and visceral C-fibre nociceptive primary afferent fibres. It is expected that vanilloid agonists will broaden the palette of analgesic drugs which do not cause addiction and tachyphylaxis.
A Pharmacological Study of the TRPV 1 Capsaicin Receptor
2006
2006 1 THEORETICAL BACKGROUND As a result of long-standing contribution of Professor János Szolcsányi, member of Hungarian Academy of Sciences, there has been great history of investigation of capsaicin (N-vanilil-8-methil-6-nonamide, spicy alcaloid of hot pepper) in our Department. According to notes, capsaicin has been widely used in folk medicine over 500 years to cure inflammations and sometimes painful conditions. Capsaicin first excites some primary afferents causing burning pain, followed by desensitization (called analgesy) and at higher concentration it can be neurotoxic Desensitization is subject of intensive research worldwide in a hope to design anti-inflammatory and pain reliever medicines. The term desensitization has two meanings: pharmacological desensitization means the decrease of receptor sensitivity against the agonist, while sensory or functional desensitization means diminution of responsiveness of nerve endings to natural stimuli. Morphological changes like sw...
Neuropharmacology, 2013
Pha1b toxin is a peptide purified from the venom of the armed spider Phoneutria nigriventer, with markedly antinociceptive action in models of acute and persistent pain in rats. Similarly to ziconotide, its analgesic action is related to inhibition of high voltage activated calcium channels with more selectivity for N-type. In this study we evaluated the effect of Pha1b when injected peripherally or intrathecally in a rat model of spontaneous pain induced by capsaicin. We also investigated the effect of Pha1b on Ca 2þ transients in cultured dorsal root ganglia (DRG) neurons and HEK293 cells expressing the TRPV1 receptor. Intraplantar or intrathecal administered Pha1b reduced both nocifensive behavior and mechanical hypersensitivity induced by capsaicin similarly to that observed with SB366791, a specific TRPV1 antagonist. Peripheral nifedipine and mibefradil did also decrease nociceptive behavior induced by intraplantar capsaicin. In contrast, u-conotoxin MVIIA (a selective N-type Ca 2þ channel blocker) was effective only when administered intrathecally. Pha1b, MVIIA and SB366791 inhibited, with similar potency, the capsaicin-induced Ca 2þ transients in DRG neurons. The simultaneous administration of Pha1b and SB366791 inhibited the capsaicin-induced Ca 2þ transients that were additive suggesting that they act through different targets. Moreover, Pha1b did not inhibit capsaicin-activated currents in patchclamp recordings of HEK293 cells that expressed TRPV1 receptors. Our results show that Pha1b may be effective as a therapeutic strategy for pain and this effect is not related to the inhibition of TRPV1 receptors.
Experimental and Therapeutic Medicine
Capsaicin is a natural protoalkaloid recognized as the main pungent component in hot peppers (Capsicum annuum L.). The capsaicin receptor is highly expressed in the unmyelinated type C nerve fibers originating from small diameter sensory neurons in dorsal root ganglia and cranial nerve ganglia correspondents. Capsaicin and related vanilloids have a variety of effects on primary sensory neurons function, from sensory neuron excitation characterized by local burning sensation and neurogenic inflammation, followed by conduction blockage accompanied by reversible ultrastructural changes of peripheral nociceptive endings (desensitization), going as far as irreversible degenerative changes (neurotoxicity). The main role in capsaicin-induced neurogenic inflammation relies on the capsaicin sensitive, small diameter primary sensory neurons, therefore its evaluation could be used as a diagnostic instrument in functional alterations of cutaneous sensory nerve fibers. Moreover, capsaicin-induced desensitization and neurotoxicity explain the analgesic/antinociceptive and anti-inflammatory effects of topical capsaicin and its potential use in the management of painful and inflammatory conditions. In this study, we describe the effects of capsaicin on neurogenic inflammation and nociception, as well as its potential diagnostic value and therapeutic impact in various conditions involving impairment of sensory nerve fibers. Contents 1. Introduction 2. Physicochemical properties of capsaicin 3. The capsaicin receptor-structure and functioning 4. Expression and roles of the capsaicin receptor 5. Capsaicin-induced neurogenic inflammation 6. Capsaicin-induced hyperalgesia 7. Capsaicin-induced desensitization 8. Capsaicin neurotoxicity 9. Conclusion
Topical Capsaicin Response as a Phenotypic Measure in Patients with Pain
Pain Medicine, 2015
Capsaicin, the active component of chili peppers, selectively activates TRPV1 transient receptor potential cation channels, expressed primarily by a subpopulation of afferent C-fibers [1]. Local topical or intradermal application of capsaicin causes burning pain, neurogenic inflammation, hyperalgesia, and a vascular flare response [2]. It yields rather reproducible pain responses in healthy volunteers [3] and is used as an experimental human pain model. More recently, Campbell et al. reported that an increased pain response to capsaicin application is associated with a better treatment response to topical clonidine in painful diabetic neuropathy, presumably linking the capsaicin response to small fiber function [4].
Neuroscience Letters, 1998
A vanilloid receptor (VR1) has recently been cloned and shown to be a target for capsaicin, the excitotoxic component of capsicum peppers (Caterina, M.J., Schumacher, M.A., Tominaga, M., Rosen, T.A., Levine, J.D. and Julius, D., Nature, 389 (1997) 816-824). The effects of capsaicin appear to be selective for a subset of sensory neurones which includes polymodal nociceptors. The present study describes the distribution of VR1 mRNA, together with measurements of capsaicin sensitivity, in sensory nerve ganglia of different embryological origins and a single sympathetic ganglion, the superior cervical ganglion (SCG). In situ hybridisation revealed the expression of VR1 mRNA in small-to-medium-sized neurones of the dorsal root, trigeminal and vagal ganglia. No hybridisation signal was observed in the SCG neurones. This pattern of expression correlated with capsaicin sensitivity measured by whole-cell voltage clamp where, in similar sized cells, over 80% of neurones from dorsal root and vagal ganglia were capsaicin sensitive, but all SCG neurones were insensitive to capsaicin.