The Effect of Intrathecal Injection of Dextromethorphan on the Experimental Neuropathic Pain Model.

Abstract

BackgroundPeripheral glucocorticoid receptors (GRs) are altered by peripheral nerve injury and may modulate the development of neuropathic pain. Two central pathogenic mechanisms underlying neuropathic pain are neuroinflammation and N-methyl-D-aspartate receptor (NMDAR)-dependent neural plasticity in the spinal cord.ObjectivesThis study examined the effect of the non-competitive NMDAR antagonist dextromethorphan on partial sciatic nerve ligation (PSL)-induced neuropathic pain and the spinal expression of the glucocorticoid receptor (GR).MethodsMale mice were randomly assigned into a sham group and two groups receiving PSL followed by intrathecal saline vehicle or dextromethorphan (iDMP). Vehicle or iDMP was administered 8 - 14 days after PSL. The hotplate paw-withdrawal latency was considered to measure thermal pain sensitivity. The spinal cord was then sectioned and immunostained for GR.ResultsThermal hyperalgesia developed similarly in the vehicle and iDMP groups prior to the injections (P = 0.828 and 0.643); however, it was completely mitigated during the iDMP treatment (P < 0.001). GR expression was significantly higher in the vehicle group (55.64 ± 4.50) than in the other groups (P < 0.001). The iDMP group (9.99 ± 0.66) showed significantly higher GR expression than the sham group (6.30 ± 1.96) (P = 0.043).ConclusionsThe suppression of PLS-induced thermal hyperalgesia by iDMP is associated with the downregulation of GR in the spinal cord, suggesting that this analgesic effect is mediated by inhibiting GR-regulated neuroinflammation.