THE ANALGESIC EFFECTS OF R(-WIN-55,212-2 MESYLATE, A HIGH-AFFINITY CANNABINOID AGONIST, IN A RAT MODEL OF NEUROPATHIC PAIN())

The effects of a high affinity cannabinoid receptor agonist were evalu ated in rats subjected to chronic constriction injury of the sciatic n erve (CCI) or a sham operation. Intraperitoneal (i.p.) injections of t he active, but not the inactive enantiomer, alleviated the pain behavi or exhibited by CCI animals in a dose dependent manner. Moreover, at d oses ranging from 0.43 to 4.3 mg/kg effects on sensitivity to a heat s timulus were observed neither in the paw contralateral to the sciatic ligation, nor in animals subjected to sham surgery. Animals subjected to CCI and treated with 4.3 mg/kg exhibited hypoalgesia in the paw ips ilateral to the ligated sciatic, i.e. heat hypoalgesia was completely reversed. The hypoalgesia is presumed to be the results of unmasking o f a sensory deficit reflecting the known loss of C and A delta with CC I. Although side effects were present in some CCI animals subjected to the high dose (4.3 mg/kg), a moderate dose (2.14 mg/kg) completely al leviated the thermal and mechanical hyperalgesia, and mechanical allod ynia without side effects, In addition to identifying a potential drug treatment for painful neuropathy, this study suggests that changes in cannabinoid receptors occurs in nerve injured animals. (C) 1997 Elsev ier Science Ireland Ltd.