Spinal administration of capsazepine inhibits noxious evoked responses of dorsal horn neurons in non-inflamed and carrageenan inflamed rats.
Vanilloid VR1 receptors are located in the dorsal horn of the spinal cord. The aim of the present study was to determine the role of spinal vanilloid receptors (VR1) during nociceptive processing in control and inflamed rats. Effects of spinal administration of capsazepine (0.5-30 microM/50 microl), a competitive VR1 antagonist, on innocuous and noxious evoked responses of spinal neurones were studied in halothane anaesthetised rats. Transcutaneous electrical-evoked neuronal responses of spinal neurones were recorded in control and carrageenan (2%, 3 h) inflamed rats. Spinal application of capsazepine did not significantly alter Abeta-fibre evoked responses of neurones, however Adelta-fibre evoked responses were significantly inhibited by capsazepine in both non-inflamed and carrageenan inflamed rats (30 microM: non-inflamed 31+/-8% of control, P<0.01: carrageenan-inflamed 43+/-6% of control, P<0.01). Similarly, the evoked C-fibre mediated post-discharge responses of spinal neurones in non-inflamed and carrageenan inflamed rats were reduced by capsazepine (30 microM: non-inflamed 41+/-14% of control, P<0.01: carrageenan-inflamed 31+/-9% of control, P<0.01). These results demonstrate a role of spinal VR1 receptors during noxious, but not innocuous transmission, at the level of the spinal cord. The degree of effect of capsazepine on evoked neuronal responses was similar in control and inflamed rats, suggesting that the role of spinal VR1 receptors is not altered following short-term peripheral inflammation. Our data suggest that following noxious peripheral stimulation, spinal VR1 receptors are activated, but the endogenous ligands mediating this effect remain to be elucidated.
Kelly
Sara
S
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG9 2UH, UK.
Chapman
Victoria
V
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology*; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*
D011955:Receptors, Drug; D002351:Carrageenan; C071423:capsazepine; D002211:Capsaicin