Papers of the Week

Neuropathic pain spreads spatially beyond the injured sites, and the mechanism underlying the spread has been attributed to inflammation occurring in the spinal cord. However, the spatial spread of spinal/cortical potentiation induced by conduction block of the peripheral nerves can be observed prior to inflammation. In the present study, we found that spreading potentiation and hypersensitivity acutely induced by unilateral hindpaw ischemia are NO-dependent and that NO is produced by ischemia and quickly diffuses within the spinal cord. We also found that NO production induced by ischemia is not observed in the presence of an antagonist for group II metabotropic glutamate receptors (mGluRs) and that neuronal NO synthase-positive dorsal horn neurons express group II mGluRs. These results strongly suggest that NO-mediated spreading potentiation in the spinal cord is one of the trigger mechanisms for neuropathic pain.