Inhibition of peripheral vanilloid TRPV1 receptors reduces noxious heat-evoked responses of dorsal horn neurons in naïve, carrageenan-inflamed and neuropathic rats.
The vanilloid TRPV1 receptor, present on primary afferent fibres, is activated by noxious heat, low pH and endogenous vanilloids. Changes in the function or distribution of TRPV1 receptors may play an important role in pain induced by inflammation or neuropathy. The aim of the present study was to evaluate the role of peripheral TRPV1 receptors in thermal nociception in rat models of inflammatory and neuropathic pain. Here, we have determined the effects of peripheral administration of the potent TRPV1 receptor antagonist iodoresiniferatoxin (IRTX) on noxious heat (45 degrees C)-evoked responses of spinal wide dynamic range (WDR) neurons in naïve, carrageenan-inflamed, sham-operated and L5/6 spinal nerve-ligated (SNL) anaesthetized rats in vivo. In addition, effects of peripheral administration of IRTX on mechanically evoked responses of WDR neurons were determined in sham-operated and SNL rats. Carrageenan inflammation significantly (P<0.05) increased the 45 degrees C-evoked responses of WDR neurons. Intraplantar injection of the lower dose of IRTX (0.004 microg) inhibited (P<0.05) 45 degrees C-evoked responses of WDR neurons in carrageenan-inflamed, but not in naïve, rats. The higher dose of IRTX (0.4 microg) significantly (P<0.05) inhibited 45 degrees C-evoked responses in both inflamed and naïve rats. In sham-operated and SNL rats, IRTX (0.004 and 0.4 microg) significantly (P<0.05) inhibited 45 degrees C-evoked, but had no effect on mechanically evoked responses of WDR neurons. These data support the role of peripheral TRPV1 receptors in noxious thermal transmission in naïve, inflamed and neuropathic rats, and suggest that there is an increased functional contribution of peripheral TRPV1 receptors following acute inflammation.
Jhaveri
Maulik D
MD
Institute of Neuroscience, School of Biomedical Sciences, E Floor, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK. maulik.jhaveri@nottingham.ac.uk
Elmes
Steven J R
SJ
Kendall
David A
DA
Chapman
Victoria
V
D000818:Animals; D002351:Carrageenan; D004195:Disease Models, Animal; D004224:Diterpenes / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005071:Evoked Potentials / Q000187:drug effects; D006358:Hot Temperature / Q000009:adverse effects*; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D008026:Ligation / Q000379:methods; D008297:Male; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects / Q000503:physiopathology; D018709:Statistics, Nonparametric; D050916:TRPV Cation Channels; D013997:Time Factors
D004224:Diterpenes; D007473:Ion Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C468130:iodoresiniferatoxin; D002351:Carrageenan