Cannabinoid receptor 2 ‑selective agonist JWH015 attenuates bone cancer pain through the amelioration of impaired autophagy flux induced by inflammatory mediators in the spinal cord.

Cannabinoid receptor 2‑selective agonist JWH015 attenuates bone cancer pain through the amelioration of impaired autophagy flux induced by inflammatory mediators in the spinal cord. Mol Med Rep. 2019 Oct 25;: Authors: Mao Y, Huang Y, Zhang Y, Wang C, Wu H, Tian X, Liu Y, Hou B, Liang Y, Rong H, Gu X, Ma Z Abstract Bone cancer pain (BCP) is a severe complication of advanced bone cancer. Although cannabinoid receptor 2 (CB2) agonists may have an analgesic effect, the underlying mechanism remains unclear. CB2 serves a protective role in various pathological states through the activation of autophagy. Therefore, the present study aimed to determine whether the analgesic effects of the selective CB2 agonist JWH015 was mediated by the activation of autophagy in BCP. BCP was induced by the intra‑femur implantation of NCTC2472 fibrosarcoma cells in C3H/HeN mice. The pain behaviors were assessed on the following postoperative days. The selective CB2 agonist JWH015 (1 and 2 µg) was intrathecally administered on day 14 following implantation. AM630 (1 µg), a CB2 antagonist, was injected 30 min before JWH015 administration. Lipopolysaccharide (LPS; 100 nM)‑stimulated primary neurons were treated with JWH015 (1 µM) and AM630 (1 µM) to further verify the mechanism by which CB2 affects autophagy. The results demonstrated that autophagy flux was impaired in spinal neurons during BCP, as indicated ...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research

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