Excessive activation of
N-methyl-D-aspartate (
NMDA) receptors in the spinal cord consequent to peripheral injury has been implicated in the initiation of neuropathologic events leading to a state of chronic hyperexcitability and persistence of exaggerated sensory processing. In other
CNS disease or injury states,
NMDA-mediated neurotoxic damage is associated with a loss of
NMDA receptors, and outcome may be improved by
agents reducing NMDA activation. Previous findings in our laboratory have demonstrated that the
transplantation of adrenal medullary tissue into the spinal subarachnoid space can alleviate sensory abnormalities and reduce the induction of a putative
nitric oxide synthase consequent to
peripheral nerve injury. In order to determine changes in
NMDA receptor expression in the spinal cord following
peripheral nerve injury and adrenal medullary grafting,
NMDA receptor binding using a high-affinity competitive
NMDA receptor antagonist,
CGP-39653, and
NMDAR1 subunit distribution using immunocytochemistry were investigated. Two weeks following
peripheral nerve injury by loose
ligation of the right sciatic nerve, either adrenal medullary or striated muscle (control) tissue pieces were implanted in the spinal subarachnoid space. Binding studies revealed a marked reduction in [3H]
CGP-39653 binding at L4-L5 levels ipsilateral to
peripheral nerve injury in control transplanted animals. In contrast,
NMDA binding was normalized in adrenal medullary grafted animals. In addition,
NMDAR1 immunoreactivity was reduced in both the dorsal horn neuropil and motor neurons of the ventral horn in animals with
peripheral nerve injury, while levels in adrenal medullary grafted animals appeared similar to intact controls. These results suggest that adrenal medullary transplants reduce abnormal sensory processing resulting from peripheral injury by intervening in the spinal
NMDA-excitotoxicity cascade.