Acute mechanical hyperalgesia is produced by coactivation of AMPA and metabotropic glutamate receptors.

Several recent reports document that activation of the NMDA receptor is required for the development and maintenance of thermal hyperalgesia. In contrast, the receptor subtype(s) involved in mechanisms that underlie mechanical hyperalgesia are at present unknown. We report here that acute mechanical hyperalgesia in the rat is not produced by NMDA receptor agonists, but instead requires coactivation of ionotropic AMPA and metabotropic glutamate receptor subtypes. Collectively, the results are consistent with a role for activation of spinal cord neurons using NMDA receptor agonists in mechanisms of thermal hyperalgesia and for coactivation of AMPA and metabotropic glutamate receptors on spinal cord neurons in mechanisms of mechanical hyperalgesia.