The cannabinoid CB2 receptor mediates the analgesic effects of Cannabis sativa extract in a rat model of neuropathic pain

Abstract

Neuropathic pain (NP) is a complex and debilitating condition that is often refractory to currently available analgesic medications. Cannabis sativa extract (CSE) has been reported to exhibit analgesic properties across various pain models; however, the underlying mechanisms of action are not fully understood. This study aimed to investigate the involvement of the cannabinoid CB2 receptor in mediating the analgesic effects of CSE in a rat model of NP, where NP was induced in male Wistar rats through chronic constriction injury (CCI) of the sciatic nerve. Rats were randomly allocated into four groups: (1) Sham + vehicle, (2) CCI + vehicle, (3) CCI + CSE, and (4) CCI + CSE + AM630 (a CB2 receptor antagonist). CSE was administered intraperitoneally at a dosage of 30 mg/kg once daily for 7 days, starting from day 7 to day 13 post-CCI surgery. To assess the involvement of the CB2 receptor, 7 µg of AM630 was administered intrathecally to the rats in group 4, 30 minutes before the CSE injections. Mechanical allodynia and thermal hyperalgesia were assessed using the von Frey filament and hot plate tests, respectively, at baseline (day 0) and on days 3, 7, 10, and 14 after surgery. Additionally, at the end of the study period (day 14), the expression level of Iba1 and GFAP genes was quantified in the lumbar enlargement tissues using real-time PCR. The results demonstrated that CCI surgery induced mechanical allodynia and thermal hyperalgesia, along with the upregulation of Iba1 and GFAP genes in the vehicle-treated CCI group. Treatment with CSE significantly mitigated both allodynia and hyperalgesia and downregulated the expression of Iba1 and GFAP genes compared to the CCI + vehicle group. Furthermore, the administration of the CB2 receptor antagonist AM630 not only robustly blocked the antinociceptive effects of CSE but also reversed the significant downregulation of Iba1 and GFAP gene expression in the lumbar enlargement tissues. These findings highlight the novel role of the CB2 receptor in mediating the analgesic effects of CSE, providing new insights into the potential therapeutic mechanisms of CSE in neuropathic pain management.