PREEMPTIVE ADMINISTRATION OF CLONIDINE PREVENTS DEVELOPMENT OF HYPERALGESIA TO MECHANICAL STIMULI IN A MODEL OF MONONEUROPATHY IN THE RAT

Traumatic nerve injury in man can often result in the development of n europathy. An animal model of neuropathic hyperalgesia is produced by loose ligation of the sciatic nerve in the rat. We have examined the e ffect of pre-emptive treatment with a number of drugs on the developme nt of hyperalgesia in this model. Animals received clonidine (1 mg.kg( -1), s.c.), morphine (5 mg. kg(-1), s.c.), (+/-)-baclofen (40 mg.kg(-1 ) s.c.), carbamazepine (50 mg.kg(-1), s.c.) or vehicle (4 ml.kg(-1), s .c.) 30min prior to loose ligation or sham-operation. Morphine- and cl onidine-treated animals were administered a second dose of drug 6h fol lowing surgery. Twenty-six or twenty-nine days following surgery, the ipsilateral (ipsi.) and contralateral (contra.) paw withdrawal thresho lds were determined using an Algesymeter. In vehicle-treated animals t he ipsilateral paw withdrawal threshold (118+/-7 g) was significantly lower (P < 0.0001, paired t-test) than the contralateral (195+/-7 g). In contrast, in animals pre-treated with clonidine no significant diff erence between ipsilateral (200+/-9 g) and contralateral (191+/-7 g) p aw withdrawal thresholds was detected. Morphine pre-treatment was less effective in preventing development of hyperalgesia; however, whilst the ipsilateral (146+/-18 g) paw withdrawal threshold tended to be low er than the contralateral (183+/-8 g), this was not significant. Twent y nine days following surgery, a significant difference (P < 0.0001) b etween ipsilateral and contralateral paw withdrawal thresholds was det ected in animals pre-treated with (+)-baclofen (ipsi., 113+/-5 g; cont ra., 170+/-5 g) or carbamazepine (ipsi., 114 + 7 g; contra., 190+/-6 g ). No significant difference in ipsilateral and contralateral paw with drawal thresholds was detected in any of the drug or vehicle pre-treat ed groups following sham-operation. Our results show that pre-treatmen t with clonidine or morphine, but not (+)-baclofen or carbamazepine pr events development of hyperalgesia in this model of neuropathy.