The effect of intrathecal guanfacine and clonidine on the flexor reflex in rats with intact and sectioned sciatic nerves

Abstract

We examined the effect of intrathecal (i.t.) administration of the non-selective α 2-adrenoceptor agonist clonidine and the α 2A- adrenoceptor selective agonist guanfacine on flexor reflex excitability in decerebrate, spinalized, unanesthetized rats before and after unilateral section of the sciatic nerve. Both guanfacine and clonidine dose dependently depressed the flexor reflex in rats with intact nerves. There was a dramatic increase in the sensitivity of the flexor reflex to the depressive effect of i.t. clonidine 4 to 18 days after sciatic nerve section. In contrast, the sensitivity to i.t. guanfacine increased only slightly. The present results suggest that the markedly increased sensitivity to the analgesic effect of the non-selective α 2-adrenoceptor agonist does not involve up-regulation of α 2A- adrenoceptors . Since radioligand binding data suggested that about 4% of spinal cord α 2- adrenoceptors are of the α 2C type, whereas α 2B- adrenoceptors are not detectable. α 2C- adrenoceptors seem to be a good candidate to mediate the up-regulated response to clonidine in axotomized rats. Thus, α 2C- adrenoceptor agonists may be useful in the treatment of neuropathic pain.