Celastrol Attenuates Inflammatory and Neuropathic Pain Mediated by Cannabinoid Receptor Type 2

International Journal of Molecular Sciences

Longhe Yang¹  Yanting Li¹  Jie Ren¹  Chenggang Zhu¹  Jin Fu¹  Donghai Lin² 

[1] Department of Medical Sciences, Medical College, Xiamen University, Xiamen 361006, China; E-Mails:;The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China

关键词: celastrol;    inflammatory pain;    neuropathic pain;    cannabinoid receptors;   

DOI  :  10.3390/ijms150813637

来源: mdpi

【 摘 要 】

Celastrol, a major active ingredient of Chinese herb Tripterygium wilfordii Hook. f. (thunder god vine), has exhibited a broad spectrum of pharmacological activities, including anti-inflammation, anti-cancer and immunosuppression. In the present study, we used animal models of inflammatory pain and neuropathic pain, generated by carrageenan injection and spared nerve injury (SNI), respectively, to evaluate the effect of celastrol and to address the mechanisms underlying pain processing. Intraperitoneal (i.p.) injection of celastrol produced a dose-dependent inhibition of carrageenan-induced edema and allodynia. Real-time PCR analysis showed that celastrol (0.3 mg/kg, i.p.) significantly reduced mRNA expressions of inflammatory cytokines, TNF-α, IL-6, IL-1β, in carrageenan-injected mice. In SNI mice, pain behavior studies showed that celastrol (1 mg/kg, i.p.) effectively prevented the hypersensitivity of mechanical nociceptive response on the third day post-surgery and the seventh day post-surgery. Furthermore, the anti-hyperalgesic effects of celastrol in carrageenan-injected mice and SNI mice were reversed by SR144528 (1 mg/kg, i.p.), a specific cannabinoid receptor-2 (CB₂) receptor antagonist, but not by SR141716 (1 mg/kg, i.p.), a specific cannabinoid receptor-1 (CB₁) receptor antagonist. Taken together, our results demonstrate the analgesia effects of celastrol through CB₂ signaling and propose the potential of exploiting celastrol as a novel candidate for pain relief.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.