Capsaicin sensitivity

This is an unconventional reflex mediated by capsaicin-sensitive primary afferent neurons. In fact, an adequate stimulus can directly excite a peripheral terminal... 

Diuretics This indicates the unique property of capsaicin-sensitive primary afferent neurons to release mediators (neuropeptides and others) from both peripheral and central nervous system terminals upon adequate stimulation. Capsaicin and other chemical (protons) or physical (heat) stimuli release mediators from both peripheral and... 

Topcu T, GULPiNAR M A, isMAN c A, YEGEN B c, YEGEN c (2002) Enterogasfric brake in rats with segmental bowel resection role of capsaicin-sensitive nerves. Clin Exp Pharmacol Physiol. 29 68-72. 

At present, two conceptually different (but not mutually exclusive) therapeutic strategies are being pursued in the vanilloid field one is to use optimized TRPVl agonists to desensitize (in practice, defunctionalize) capsaicin-sensitive nerves [1, 21] and the other is to employ small molecule antagonists for the pharmacological blockade of TRPVl [7, 8]. The first approach is time-proven, but is riddled by known side-effects such as pain [1], as well as emerging concerns such as impaired control of cancerous growth [22]. 

In capsaicin-sensitive neurons, TRPVl is co-expressed with various receptors involved in pain perception (e.g. bradykinin B2, purine P2X3). There is important cross-talk among these receptors. For example, stimulation... 

TRPVl also plays a central role in intercellular pro-inflammatory feedback loops. An important example is mast cells and sensory nerves. Mast cells release tryptase that, in turn, activates the protease-activated receptor PAR-2 activation of PAR-2 then opens TRPVl via PKC [50]. In keeping with this, PAR-2 agonists reduce the heat activation threshold of TRPVl from 42 °C to below body temperature [51]. Excited nerve endings release SP that, as a positive feedback, binds to neurokinin NKl receptors on mast cells. Mast cells also express TRPVl [52]. Consequently, endovanilloids can act in concert to stimulate mast cells and activate capsaicin-sensitive nerve endings. Of relevance is the finding that PAR-2 is up-regulated in the bladder during experimental cystitis [53]. 

Nevertheless, RR is clearly a non-competitive antagonist that blocks the channel pore [2] with no effect on [ H]RTX binding [4]. RR was useful in dissecting responses mediated by capsaicin-sensitive nerves in vitro, but its use in animals was severely restricted by the toxicity (e.g. convulsive activity) that it caused [1]. 

Capsaicin-sensitive nerves sense bladder fullness and form the afferent limb of the micturition reflex [132]. In conditions of bladder hypersensitivity, TRPVl is up-regulated on these nerves (presumably via NGL [133, 134]) and deafferentation of the bladder by intravesical capsaicin or RTX was proven beneficial [135-137]. Parenthetically, intravesical RTX is also an effective analgesic agent during experimental cystitis in the rat [138]. By... 

Helliwell, R.J., McLatchie, L.M., Clarke, M., Winter, J., Bevan, S., McIntyre, P. Capsaicin sensitivity is associated with the expression of the vanilloid (capsaicin) receptor (VR1) mRNA in adult rat sensory ganglia, Neurosci. Lett. 1998, 250, 177-180. 

Sasamura, T., Sasaki, M., Tohda, C., Kuraishi, Y. Existence of capsaicin-sensitive glutamatergic terminals in rat hypothalamus, Neuroreport 1998, 9, 2045-1048. 

Winter, J., Walpole, C.S., Bevan, S., James, I.F Characterization of resiniferatoxin binding sites on sensory neurons co-regulation of resiniferatoxin binding and capsaicin sensitivity in adult rat dorsal root ganglia, Neuroscience 1993, 57, 747-757. 

Ahluwalia J, Urban L, Bevan S, Nagy I (2003) Anandamide regulates neuropeptide release from capsaicin-sensitive primary sensory neurons by activating both the cannabinoidl receptor and the vanilloid receptorl in vitro. Eur J Neurosci 17 2611-18... 

Kawamata, T., Omoto, K., Toriyabe, M., Kawamata, M., and Namiki, A. (2001). Involvement of capsaicin-sensitive fibers in spinal NMDA-induced glutamate release. Neuroreport 12, 3447-3450. Kite, S. M., Maher, E. J., Anderson, K., Young, T., Young, J., Wood, J., Howell, N., and Bradburn, J. 

Hamon M, Gallissot MC, Menard F, Gozlan H, Bourgoin S, Verge D. 5-HT3 receptor binding sites are on capsaicin-sensitive fibres in the rat spinal cord. Eur J Pharmacol 1989 164 315-322. 

Del Mar LP, Cardenas CG, Scroggs RS. Serotonin inhibits high-threshold Ca2+ channel currents in capsaicin-sensitive acutely isolated adult rat DRG neurons. J Neurophysiol 1994 72 2551-2554. 

Maggi CA, Giuliani S, Santicioli P et al. (1987) Further studies on the mechanisms of the tachykinin-induced activation of the micturition reflex in rats evidence for the involvement of the capsaicin-sensitive bladder mechanoreceptors. Eur J Pharmacol 136 189-205... 

Maggi CA, Giuliani S (1992) Non-adrenergic, non-cholinergic excitatory innervation of the guinea pig renal pelvis Involvement of capsaicin-sensitive primary afferent neurons. J Urol 147 1394-1398... 

Sorkin LS, Yu AL, lunger H, Doom CM (2002) Antibody directed against GD2 produces mechanical allodynia, but not thermal hyperalgesia when administered systemically or intrathecaUy despite its dependence on capsaicin sensitive afferents. Brain Res 930 67—74 Sorrells SF, Sapolsky RM (2007) An inflammatory review of glucocorticoid actions in the CNS. Brain Behav Immun 21 259-272... 

Lundberg, J.M., Saria, A. (1982). Bronchial smooth muscle contraction induced by stimulation of capsaicin-sensitive sensory neurons. Acta Physiol. Scand. 116 473-6. 

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