Peripheral NMDA receptors contribute to activation of nociceptors: a c-fos expression study in rats

By using immunocytochemical techniques, we demonstrated that: (1) unilateral injection of N-methyl- d-aspartate (NMDA; 10, 20, 50 μmol) into the plantar aspect of hindpaw of the normal waked rats elicited a dose-dependent increase of c-fos expression in the superficial laminae on the side of the spinal dorsal horn ipsilateral to the injection; (2) combined injection of MK-801, a non-competitive NMDA receptor antagonist, with formalin into the hindpaw could suppress formalin-induced c-fos expression in the dorsal horn, with a stronger suppression after higher doses of MK-801 being injected. These results strongly suggest that NMDA receptors might be located in the membrane of peripheral axonal terminals of the dorsal root ganglion neurons and might be involved in the activation of nociceptors.