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Int. J. Mol. Sci. 2014, 15(8), 13637-13648; doi:10.3390/ijms150813637

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

1
Department of Medical Sciences, Medical College, Xiamen University, Xiamen 361006, China
2
The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
*
Authors to whom correspondence should be addressed.
Received: 9 May 2014 / Revised: 9 June 2014 / Accepted: 16 June 2014 / Published: 6 August 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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. View Full-Text
Keywords: celastrol; inflammatory pain; neuropathic pain; cannabinoid receptors celastrol; inflammatory pain; neuropathic pain; cannabinoid receptors
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Yang, L.; Li, Y.; Ren, J.; Zhu, C.; Fu, J.; Lin, D.; Qiu, Y. Celastrol Attenuates Inflammatory and Neuropathic Pain Mediated by Cannabinoid Receptor Type 2. Int. J. Mol. Sci. 2014, 15, 13637-13648.

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