The spinal analgesic role of α2-adrenoceptor subtypes in rats after peripheral nerve section

Abstract

Two putative agonists of subtypes of α 2-adrenoceptors, guanfacine ( α 2A) and ST-91 (2-[2,6-dicthylphenylaminol]-2-imidazoline, α 2C), were applied intrathecally and their effects on autotomy behaviour and on the flexor reflex before and after sciatic nerve section were examined. Neither drug influenced autotomy during a 17-day observation period. Both drugs dose dependently depressed the flexor reflex in rats with intact sciatic nerves. After axotomy, the sensitivity of the flexor reflex to guanfacine and ST-91 was moderately increased compared to normals. ST-91 i.t. at high doses evoked motor discharges, an effect which was reversed by the α 1-adrenoceptor antagonists, WB4101 (2-[2,6-dimethoxyphenoxyethyl]-aminomethyl-1,4-benzodioxane). Thus, the effect of i.t. clonidine on the flexor reflex and autotomy behaviour observed previously may not involve its action on α 2A- and α 2C-adrenoceptors. Furthermore, due to its motor effect which may involve activation of α 1-adrenoceptors, ST-91 may not be a suitable tool to study the physiological function of spinal α 2C-adrenoceptors.