SPINAL-CORD NMDA RECEPTORS MODULATE PERIPHERAL IMMUNE-RESPONSES AND SPINAL-CORD C-FOS EXPRESSION AFTER IMMUNE CHALLENGE IN RATS SUBJECTED TO UNILATERAL MONONEUROPATHY

To characterize further the neural involvement in local immune reactio ns, we evaluated the effect of intrathecal NMDA-receptor blocker dizoc ilpine maleate (MK-801) on the peripheral immune response itself and o n spinal cord c-fos expression induced by the delayed-type hypersensit ivity (DTH) response. Immune challenge took place in the hind paw ipsi lateral or contralateral to an injured sciatic nerve in both previousl y sensitized and immune-naive animals. An enhanced immune response was observed bilaterally in the hind paws of animals subjected to unilate ral mononeuropathy compared with sham-operated controls. In contrast, no such enhancement was observed when neuropathic animals were challen ged in the front paws. The increased DTH response was blocked successf ully by the intrathecal administration of an analgesic dose of MK-801. Compared with sham-operated animals, animals subjected to unilateral mononeuropathy showed both a differential distribution and an increase in the number of c-fos-labeled neurons in the dorsal horn of the L3-L 5 spinal cord segments after immune challenge. This was observed irres pective of whether the challenge took place ipsilateral or contralater al to the injured nerve, In addition to reversing the changes in immun e response, intrathecal administration of MK-801 reversed the pattern of c-fos immunoreactivity in the spinal cord after immune challenge in neuropathic animals. These data suggest that select groups of spinal cord neurons participate in enhancing the peripheral immune response t o a specific antigen in neuropathic animals and that this enhancement involves central NMDA receptors.