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

Abstract

Background: Peripheral 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. Objectives: This 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). Methods: Male 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. Results: Thermal 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). Conclusions: The 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.