Pain behaviors produced by capsaicin: influence of inflammatory mediators and nerve injury.
The present study was undertaken to characterize spontaneous (ie, nonevoked) pain behaviors (flinching, biting/licking) produced by local injections of capsaicin into the rat hindpaw as a model of chemogenic pain, and to determine effects of inflammatory mediators and nerve injury on such behaviors. Capsaicin antagonists are a potential class of novel topical analgesics, and this model may be of value for preclinical screening of novel compounds. Local injections of capsaicin (0.1-30 microg) into the hindpaw produced flinching and biting/licking behaviors over 5 min, and these were reduced by capsazepine, a competitive antagonist for capsaicin at the TRPV1 receptor. Coadministration of noradrenaline (NA), prostaglandin E(2) (PGE(2)), and 5-hydroxytryptamine (5-HT) augmented capsaicin-evoked responses primarily by extending the duration of behaviors. Partial sciatic nerve ligation decreased flinching produced by capsaicin alone, by capsaicin in combination with each of NA, PGE(2), and 5-HT, and by formalin. Tibial nerve injury also reduced capsaicin-evoked flinching, and responses to formalin, but spinal nerve ligation did not affect either. These results indicate that (1) spontaneous pain behaviors occur as a result of TRPV1 receptor activation with a different time course than evoked responses, (2) inflammatory mediators augment capsaicin-evoked pain behaviors, and (3) various forms of nerve injury produce different effects on capsaicin-evoked pain behaviors.


CONCLUSIONS
The VR1 receptor is a potential target for development of novel topical analgesics. This study characterized pain behaviors produced by local injections of capsaicin in the presence of inflammatory mediators and following various forms of nerve injury. Results are of interest for the preclinical screening of novel VR1 receptor antagonists.
Sawynok
Jana
J
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada. jana.sawynok@dal.ca
Reid
Allison
A
Meisner
Jason
J
D000818:Animals; D001522:Behavior, Animal; D002211:Capsaicin; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000502:physiology*; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000523:psychology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries*; D050916:TRPV Cation Channels / Q000502:physiology*
D018836:Inflammation Mediators; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D002211:Capsaicin