ADRENAL-MEDULLARY IMPLANTS REDUCE TRANSSYNAPTIC DEGENERATION IN THE SPINAL-CORD OF RATS FOLLOWING CHRONIC CONSTRICTION NERVE INJURY

Peripheral nerve injury causes abnormal sensory processing, possibly d ue in part to neuroplastic changes in the CNS. Following chronic const riction injury of the sciatic nerve, transsynaptic degeneration is sug gested by the presence of ''dark neurons'' found in superficial lamina e of spinal cord. Previous studies in our laboratory have shown that g rafts of adrenal medullary cells into the spinal subarachnoid space ca n reduce abnormal pain due to peripheral nerve injury. A possible mech anism for these beneficial effects is the reduction or interruption of excitotoxic events that lead to pathological CNS changes. In order to examine this, 2 weeks after unilateral sciatic nerve ligation using a chronic constriction injury model, animals received either adrenal me dullary or control striated muscle tissue implanted in the lumbar suba rachnoid space. Control striated muscle-transplanted animals with nerv e injury displayed thermal hyperalgesia and elevated numbers of dark n eurons in the superficial dorsal horn, compared to intact animals. The se dark neurons were increased bilaterally, but predominantly ipsilate rally, to nerve injury. In contrast, in animals with adrenal medullary transplants, reduced numbers of dark neurons were found in parallel w ith reduced hyperalgesia. The low numbers of dark neurons in these ani mals were similar to age-matched unoperated controls. Two months after nerve ligation, dark neurons were not found in animals with nerve inj ury although abnormal ruffled-appearing neurons were still present in untransplanted animals, suggesting partial recovery of damaged spinal neurons. The results of this study suggest that spinal adrenal medulla ry transplants can attenuate the neuropathological events perpetuating nerve-injury-induced pain by enhancing recovery of spinal neurons fro m excitotoxic insult. (C) 1996 Academic Press, Inc.