GRM5 and neuropathy: However, in the case of long-term peripheral noxious events evoking high-frequency discharges in nociceptive primary afferents such as peripheral inflammation, the release of pruritogen agents or neuropathy, excess glutamate that is released from nociceptive axon terminals may reach the perisynaptic zone of the postsynaptic membrane and activate the mGluR5-DAG-lipase complex, resulting in the release of 2-AG.