Antinociceptive effect of trans-resveratrol in rats: Involvement of an opioidergic mechanism.
trans-Resveratrol, a polyphenolic compound with potent antioxidant activity has recently been shown to be effective against carrageenan-induced hyperalgesia. In the present study, the effect of graded doses of trans-resveratrol was studied using a hot plate analgesiometer in rats. trans-Resveratrol at graded doses of 5, 10, 20 and 40 mg/kg i.p. produced dose-dependent analgesia. Pretreatment (20 min) with naloxone (1 mg/kg i.p.) blocked the analgesic effect. When the submaximal dose of trans-resveratrol (5 mg/kg i.p.) was combined with a submaximal dose of morphine (2 mg/kg i.p.), a potentiation effect was observed. The effect of trans-resveratrol (20 mg/kg i.p.) was also studied on morphine tolerance. Rats were divided into different groups: Group 1: morphine (10 mg/kg i.p.); Group 2: trans-resveratrol (5 mg/kg i.p.) administered 10 min before morphine (2 mg/kg i.p.); Group 3: trans-resveratrol (20 mg/kg i.p.) per se. Vehicle treated groups were run parallel. The treatment continued for 7 days. The occurrence of tolerance was estimated by comparing the antinociceptive effect of morphine with trans-resveratrol on day 1 and day 8. Both morphine and trans-resveratrol produced tolerance. However, in the group that received the combination of submaximal doses of trans-resveratrol and morphine, there was insignificant tolerance. These findings suggest that trans-resveratrol analgesia is mediated via an opioidergic mechanism and produces tolerance to its analgesic effect similar to morphine.
Gupta
Y K
YK
Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India. ykg@hotmail.com
Sharma
M
M
Briyal
S
S
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007194:India; D007274:Injections, Intraperitoneal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics; D009270:Naloxone / Q000008:administration & dosage / Q000493:pharmacokinetics; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010936:Plant Extracts / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D000077185:Resveratrol; D012717:Sesquiterpenes; D013267:Stilbenes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013729:Terpenes; D013997:Time Factors; D000094162:Phytoalexins
D000700:Analgesics; D010936:Plant Extracts; D011957:Receptors, Opioid; D012717:Sesquiterpenes; D013267:Stilbenes; D013729:Terpenes; D009270:Naloxone; D009020:Morphine; D000077185:Resveratrol; D000094162:Phytoalexins