Antihyperalgesic effect of the cannabinoid agonist WIN55,212-2 is mediated through an interaction with spinal metabotropic glutamate-5 receptors in rats.

In the current study, a possible interaction between spinal cord dorsal horn cannabinoid and mGlu5 receptors was evaluated in rats with a peripheral nerve injury. Following unilateral loose ligation of a sciatic nerve, rats developed decreased withdrawal thresholds to noxious pressure (mechanical hyperalgesia) of the ligated but not the unoperated contralateral hind paw. Systemic (subcutaneous) injection of synthetic cannabinoid agonist WIN55,212-2 increased withdrawal thresholds of both the ligated and the unoperated hind paw. Systemic injection of 2-methyl-6-(phenylethynyl)pyradine (MPEP), an antagonist selective for the mGlu5 receptor, did not alter the antinociceptive and antihyperalgesic effects of systemic WIN55,212-2. Intrathecal (i.t.) injection of WIN55,212-2 increased thresholds of the ligated but not the unoperated hind paw. Intrathecal injection of MPEP reversed the antihyperalgesic effect of i.t. WIN55,212-2. Neither systemic nor i.t. injection of MPEP alone altered withdrawal thresholds. These data suggest that the antihyperalgesic effect of WIN55,212-2 is mediated through an interaction with spinal mGlu5 receptors.