Neonatal capsaicin treatment prevents the development of the thermal hyperalgesia produced in a model of neuropathic pain in the rat.
Loose ligation of the sciatic nerve with 4-0 chromic gut sutures in rats produces behavioral evidence of neuropathic pain. In the present experiments we examined the involvement of capsaicin-sensitive afferents in mediating the thermal hyperalgesia produced by this model. Male Sprague-Dawley rats, treated as neonates (within 48 h of birth) with capsaicin (50 mg/kg, s.c.) or vehicle, were used at 16-18 weeks of age. Chromic gut sutures (4-0) were tied around the left sciatic nerve and withdrawal latencies of both hind paws to radiant heat were determined on postoperative days 3, 5, 10 and 20. Whereas there was a pronounced thermal hyperalgesia which lasted for up to 20 days in vehicle-treated rats, there was no evidence of thermal hyperalgesia in capsaicin-treated rats. There was no difference in baseline (pre-surgery) withdrawal latencies between the two groups. Radioimmunoassay revealed that there was a significant depletion of substance P (43.8%) and calcitonin-gene-related peptide (72.6%) in the lumbar spinal cord of neonatal capsaicin-treated rats compared to vehicle-treated rats. These results demonstrate that the chromic gut-induced thermal hyperalgesia is mediated by capsaicin-sensitive afferents and suggest that central mechanisms which process and control the reflex response to heat are different than mechanisms involved in thermal hyperalgesia.
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D004195:Disease Models, Animal; D006358:Hot Temperature; D008297:Male; D009422:Nervous System Diseases / Q000150:complications / Q000517:prevention & control*; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000502:physiology; D013373:Substance P / Q000276:immunology / Q000378:metabolism
D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin