Peripheral group II metabotropic glutamate receptors mediate endogenous anti-allodynia in inflammation

We previously demonstrated that activation of peripheral group II mGluRs inhibits PGE2-induced thermal hyperalgesia. In the present study we examined the role of peripheral group II mGluRs in inflammation-induced mechanical allodynia in CD1 mice. Subcutaneous injection of group II mGluR agonists or antagonists into the plantar surface of the mouse hind paw did not alter mechanical thresholds, suggesting that peripheral group II mGluRs did not modulate basal mechanical sensation. We then used either PGE2 or carrageenan to induce mechanical allodynia and investigated the effects of activating or inhibiting peripheral group II mGluRs. PGE2-injected mice showed an 87 +/- 1% decrease of mechanical thresholds 75 min after the injection, whereas mice injected with group II mGluR agonists had no increase in sensitivity compared to vehicle-injected mice. In the carrageenan-induced inflammation model, 3 h after carrageenan injection the mechanical thresholds of mice injected with group II mGluR agonist APDC fully recovered to baseline levels while vehicle-injected mice showed only 43 +/- 8% recovery. The application of group II mGluR antagonist (LY341495) alone delayed the recovery of PGE2- and carrageenan-induced mechanical allodynia. Three hours after injection of carrageenan, LY341495-injected mice showed little or no recovery with mechanical thresholds 8 +/- 1% of pre-carrageenan baselines, compared to 57 +/- 8% of pre-carrageenan baselines in vehicle-injected mice at the same time point. Our results suggest that activation of peripheral group II mGluRs reduces inflammation-induced mechanical allodynia and that peripheral group II mGluRs may mediate endogenous anti-allodynia effects, which speed recovery from inflammation-induced hypersensitivity. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.