Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice

Aim： Gelsemine, an alkaloid from the Chinese herb Gelsemium elegans （Gardn ＆ Champ） Benth, is effective in mitigating chronic pain in rats. In the present study we investigated whether the alkaloid improved sleep disturbance, the most common comorbid symptoms of chronic pain, in a mouse model of neuropathic pain. Methods： Mice were subjected to partial sciatic nerve ligation （PSNL）. After the mice were injected with gelsemine or pregabalin （the positive control） intraperitoneally, mechanical allodynia and thermal hyperalgesia were assessed, and electroencephalogram （EEG）/ electromyogram （EMG） recording was performed. Motor performance of the mice was assessed using rota-rod test. c-Fos expression in the brain was analyzed with immunohistochemical staining. Results： In PSNL mice, gelsemine （2 and 4 mg/kg） increased the mechanical threshold for 4 h and prolonged the thermal latencies for 3 h. Furthermore, gelsemine （4 mg/kg, administered at 6：30 AM） increased non-rapid eye movement （non-REM, NREM） sleep, decreased wakefulness, but did not affect REM sleep during the first 3 h in PSNL mice. Sleep architecture analysis showed that gelsemine decreased the mean duration of wakefulness and increased the total number of episodes of NREM sleep during the first 3 h after the dosing. Gelsemine （4 mg/kg） did not impair motor coordination in PSNL mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of the anterior cingulate cortex, and gelsemine （4 mg/kg） decreased c-Fos expression by 58%. Gelsemine （4 mg/kg, administered at either 6：30 AM or 8：30 PM） did not produce hypnotic effect in normal mice. Pregabalin produced similar antinociceptive and hypnotic effects, but impaired motor coordination in PSNL mice. Conclusion： Gelsemine is an effective agent for treatment of both neuropathic pain and sleep disturbance in PSNL mice; anterior cingulate cortex might play a role in the hypnotic effects of gelsemine.