Our photopharmacological tools allowed us to establish that pharmacological blockade of mGlu5 receptors in the contralateral mPFC caused antinociception in the CCI model of neuropathic pain, and that prelimbic and infralimbic regions, but not anterior cingulate cortex, play a critical role in mediating systemic mGlu5 NAM antinociception. Here, GRM5 is linked to neuropathic pain.