Effects of intrathecal injection of GABA_B receptor agonist baclofen on hyperalgesia and spinal GAT-1 of neuropathic rats

Aim To explore the effects of intrathecal injection of GABAB receptor agonist baclofen on hyperalgesia and spinal GAT-1 of neuropathic rats induced by chronic constriction of sciatic nerve.Methods The left common sciatic nerve of anesthetized rats was tied loosely to establish the chronic constriction injury(CCI) model.For the behavioral experiments,32 rats exhibiting neuropathic pain after nerve ligation were divided into 4 groups(n=8): NS group,Bac1 group,Bac2 group and Bac3 group,which were intrathecally injected with normal saline,0.1,0.3 and 1.0 μg baclofen respectively.MWT(mechanical withdrawl threshold)and TWL(thermal withdrawl latency) were recorded before drug administration,0.5,1,2,4,8,12 h and 24 h after drug administration respectively.For the immunohistochemical and Western blot experiment,neuropathic rats were divided into NS group and Bac group,which were intrathecally injected with normal saline or 0.3 μg baclofen respectively.Lumbar spinal cord of rats were removed before injection or 1,4 and 8 h after intrathecal injection respectively to detect the GAT-1 immunoreactive neurons(n=6) or were removed before injection or 0.5,1,2,4,8,12 h and 24 h after intrathecal injection respectively to detect the protein content of GAT-1(n=4).Results MWT and TWL of Bac1,Bac2 and Bac3 group were significantly higher than those of NS group(P0.01,P0.05).Compared with NS group,the increases of MWT and TWL in Bac1,Bac2 and Bac3 group were maintained until 8h after baclofen injection(P0.01,P0.05).Compared with NS group and pre-drug values,both immunoreactive neurons and protein content of GAT-1 remarkably decreased during 0.5~4 h after drug administration.On 8h after drug administration,there were no significant differences in the expression of GAT-1 among the four groups(P0.05).Conclusion Intrathecal injection of GABAB receptor agonist baclofen alleviates hyperalgesia of neuropathic rats with chronic constriction injury,which may be related to the down-regulation of spinal GAT-1.