OBJECTIVETo investigate the effects of intrathecal escin and clonidine, used alone or in combination, in the treatment of neuropathic pain in rats and the possible mechanism.

METHODSNinety-six male SD rats weighing 250-300 g were chronically implanted with lumbar intrathecal catheters. One week later, the left L5 and L6 spinal nerve roots were ligated to establish the model of spinal nerve ligation neuropathic pain (SNL). The rats were then randomly divided into 16 groups (n=6), including the control (saline), escin, clonidine, escin+clonidine, and the antagonist groups. Mechanical withdrawal threshold was assessed before and at 5, 10, 20, 30, 40, 50 and 60 min after intrathecal administration was evaluated. The maximal possible effect (MPE) was calculated and the effect of the treatments on the neuropathic pain. Isobolographic analysis was performed to characterize any potential interactions between the drugs.

RESULTSMPE was significantly higher in escin group (20, 40 microg), clonidine group (2, 5, 10 microg) and escin+clonidine group [1/4, 1/2 (escin ED(50)+clonidine ED(50))] than in the saline group (P<0.05). Intrathecal escin (5-40 microg) or clonidine (1-10 microg) alone dose-dependently alleviated neuropathic pain. Isobolographic analysis suggested a synergistic effect between escin and clonidine. Intrathecal pretreatment with yohimbine (20 microg) antagonized the effects of clonidine (P<0.01) and attenuated the action of the combination treatment with escin and clonidine (P<0.05).

CONCLUSIONIntrathecal escin and clonidine alone can dose-dependently relieve neuropathic pain. Escin and clonidine produce a synergistic effect for pain relief, which may involve the actions of alpha(2) receptor and Ca(2+) channel.