Objective To observe the effects of intrathecal injection(IT)of agonist and antagonist of cannabinoid receptor 1 on pain threshold in rat model of sciatic nerve ligation(SNL)induced neuropathic pain,and investigate the role and mechanism of CB1 in neuropathic pain. Methods Male Sprague-Dawley rats were randomly divided into 4 groups:sham group( intrathecal normal saline,IT DMSO),SNL group(SNL+IT 30μL DMSO),AM841 group(SNL+IT 5μg AM841,dissolved in 30μL of DMSO)and AM281 group(SNL+IT 5μg AM281,dissolved in 30μL of DMSO). IT was given 3 days before surgery. Sham group only had sciatic nerve exposure but without ligation. SNL model in the other three groups were established by right sciatic nerve ligation. The thermal and mechanical thresholds were assessed by paw withdrawal latency(PWL)to radiant heat and von Frey filaments at 1,3,5,7,10 and 14 days as well as behavior after SNL. Spinal expressions of CB1 were assessed by West-ern blotting. Results Compared with the sham group,symptoms of rats in SNL group,such as heat hyperalgesia,mechanical allodynia and poste-rior paws prone to close together,were gradually appeared in the observation time points,with lower spinal proteins expression of CB1(P<0.05). AM841 group exhibited increased proteins expression of CB1 and inhibited SNL-induced heat hyperalgesia and mechanical allodynia(P<0.05). AM281 group further decreased expression of CB1 and amplified the pain abnormality(P<0.05). Conclusion Spinal CB1 participates in the regulation of neuropathic pain,and exogenous cannabinoid CB1 agonists can alleviate the SNL-induced neuropathic pain.