Involvement of central cannabinoid CB 2 receptor in reducing mechanical allodynia in a mouse model of neuropathic pain

Abstract

We sought to examine the involvement of central cannabinoid CB 2 receptor activation in modulating mechanical allodynia in a mouse model of neuropathic pain. JWH133 was demonstrated to be a selective cannabinoid CB 2 receptor agonist in mice, reducing forskolin-stimulated cAMP production in CHO cells expressing mouse cannabinoid CB 2 and cannabinoid CB 1 receptors with EC 50 values of 63 nM and 2500 nM, respectively. Intrathecal administration of JWH133 (50 and 100 nmol/mouse) significantly reversed partial sciatic nerve ligation-induced mechanical allodynia in mice at 0.5 h after administration. In contrast, systemic (intraperitoneal) or local (injected to the dorsal surface of the hindpaw) administration of JWH133 (100 nmol/mouse) was ineffective. Furthermore, the analgesic effects of intrathecal JWH133 (100 nmol/mouse) were absent in cannabinoid CB 2 receptor knockout mice. These results suggest that the activation of central, but not peripheral, cannabinoid CB 2 receptors play an important role in reducing mechanical allodynia in a mouse model of neuropathic pain.