The antinociceptive effect of intrathecal CB2 cannabinoid receptor agonist (JWH015) in rats with chronic compression of the dorsal root ganglia

Abstract

Objective To test whether activation of CB2 receptor would induce antinociception and investigate the role of in-trathecal JWH015 in the modulation of Tyr-1472 phosphorylation of the spinal NR2B subunit in a model of neuropathic pain. Meth-otis 84 male SD rats with intrathecal catheter insertion were randomly divided into 3 groups: sham + 50% DMSO group (Sham group); CCD + 50%DMSO group(Vehicle group); CCD+JWH015 group(JWH015 group). Seven days after Sham or CCD(without in-trathecal injection), the lumbosacral spinal cords of 6 Sham rats and 6 CCD rats were collected for immunohistochemical study to de-termine the spinal expression of Tyr-1472 phosphorylated NR2B subunit(baseline). The rest were intrathcally injected with 50%DMSO 10 μl or JWH015 10 μg seven days after Sham or CCD. For behavioral studies, the data of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in Sham group or CCD group, before intrathecal injection and 1, 2, 4, 8, 24, 72 h after intrathecal injection (n=6). For immunohistochemical study, the lumbosacral spinal cords were collected 4, 8, 24, 72 h after intrathecal injection(n=6). Results Compared with the baseline before operation, the PWMT and the PWTL of Vehicle group and JWHOI5 group began to decrease before intrathecal injection(P 0.05). Tyr-1472 phosphorylated NR2B subunit expression in the superficial dorsal horn was weak in all sham groups, but increased significantly 7 days after CCD. While intrathecal 50%DMSO did not decrease the expres-sion of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn, the expression of Tyr-1472 phosphorylated NR2B sub-unit in the superficial dorsal horn decreased obviously 4 h and 8 h after intrathcal JWH015. However, the expression of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn increased again 24 h and 72 h after intrathcal JWH015. Conclusion In-trathecal administration of CB2 receptor agonist JWHOI5 may provide analgesic effect, which is probably attributed to the decrease in the spinal expression of Tyr-1472 phosphorylated NR2B subunit. Key words: Neuropathic pain; Spinal cord; JWH015; NR2B subunit; Phosphorylation