EFFECTS OF SYSTEMIC CARBAMAZEPINE AND GABAPENTIN ON SPINAL NEURONAL RESPONSES IN SPINAL NERVE LIGATED RATS

There are few pharmacological studies of central neuronal measures in animal models of neuropathic pain. In the present study we have compar ed the effects of two anticonvulsants, carbamazepine and gabapentin, o n spinal neuronal responses of nerve injured rats (selective ligation of spinal nerves L5 and L6, SNL) and sham-operated rats. The developme nt and maintenance of cooling and mechanical allodynia of the lesioned hindlimb of SNL rats was followed with behavioural indices. The contr alateral hindlimb of SNL rats and the ipsilateral hindlimb of sham-ope rated rats did not develop allodynia. Electrophysiological studies of SNL rats were then performed at two post-operative (PO) time points (P O days 7-10 and PO days 14-17). Spinal neurones of SNL rats, but not s ham-operated rats, exhibited spontaneous activity at both PO days 7-10 and 14-17 (1 +/- 0.4 and 3 +/- I Hz, respectively). Paradoxically, th e magnitude of electrical (C-fibre) and natural (mechanical and therma l) evoked neuronal responses of SNL rats at PO days 14-17 were smaller than the evoked neuronal responses of SNL rats at PO days 7-10 and sh am-operated rats. The electrical evoked A-fibre responses of neurones were comparable for the three groups of rats. Both subcutaneous carbam azepine (0.5-22.5 mg/kg) and gabapentin (10-100 mg/kg) significantly r educed the spontaneous activity of spinal neurones of SNL rats at both PO time points. Carbamazepine had inhibitory effects on electrical C- and A-fibre and mechanical punctate (9 and 50 g) evoked neuronal respo nses of SNL rats which were significantly different to the lack of eff ect of carbamazepine on these measures in sham-operated rats. Gabapent in had comparable effects as carbamazepine on the electrical C-and A-f ibre and mechanical punctate (9 and 50 g) evoked neuronal responses of SNL rats. In contrast to carbamazepine, gabapentin also reduced evoke d neuronal responses of sham-operated rats and there was no difference between the effects of gabapentin in SNL and sham-operated rats. Robu st behavioural changes in the SNL model of neuropathy are paralleled b y a temporal increase in spontaneous activity and a paradoxical decrea se in evoked spinal neuronal responses. The peripheral nerve dysfuncti on reveals an effect of carbamazepine which is maintained throughout t he observation period, validating this experimental approach. Gabapent in, a novel treatment for neuropathic pain states, also reduced neuron al responses, but the actions of the drug were not dependent on nerve injury. Further studies at the spinal level may shed light on the phys iology and pharmacology of the aberrant processes associated with neur opathic pain. (C) 1998 International Association for the Study of Pain . Published by Elsevier Science B.V.