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Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice.
Acta Pharmacol Sin. 2015 Nov; 36(11):1308-17.AP

Abstract

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.

Authors+Show Affiliations

State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26388157

Citation

Wu, Yu-er, et al. "Gelsemine Alleviates Both Neuropathic Pain and Sleep Disturbance in Partial Sciatic Nerve Ligation Mice." Acta Pharmacologica Sinica, vol. 36, no. 11, 2015, pp. 1308-17.
Wu YE, Li YD, Luo YJ, et al. Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice. Acta Pharmacol Sin. 2015;36(11):1308-17.
Wu, Y. E., Li, Y. D., Luo, Y. J., Wang, T. X., Wang, H. J., Chen, S. N., Qu, W. M., & Huang, Z. L. (2015). Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice. Acta Pharmacologica Sinica, 36(11), 1308-17. https://doi.org/10.1038/aps.2015.86
Wu YE, et al. Gelsemine Alleviates Both Neuropathic Pain and Sleep Disturbance in Partial Sciatic Nerve Ligation Mice. Acta Pharmacol Sin. 2015;36(11):1308-17. PubMed PMID: 26388157.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice. AU - Wu,Yu-er, AU - Li,Ya-dong, AU - Luo,Yan-jia, AU - Wang,Tian-xiao, AU - Wang,Hui-jing, AU - Chen,Shuo-nan, AU - Qu,Wei-min, AU - Huang,Zhi-li, Y1 - 2015/09/21/ PY - 2015/05/05/received PY - 2015/06/07/accepted PY - 2015/9/22/entrez PY - 2015/9/22/pubmed PY - 2016/8/20/medline SP - 1308 EP - 17 JF - Acta pharmacologica Sinica JO - Acta Pharmacol Sin VL - 36 IS - 11 N2 - 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. SN - 1745-7254 UR - https://www.unboundmedicine.com/medline/citation/26388157/Gelsemine_alleviates_both_neuropathic_pain_and_sleep_disturbance_in_partial_sciatic_nerve_ligation_mice_ L2 - https://doi.org/10.1038/aps.2015.86 DB - PRIME DP - Unbound Medicine ER -