Adrenal Medullary Implants Reduce Transsynaptic Degeneration in the Spinal Cord of Rats Following Chronic Constriction Nerve Injury

Abstract

Peripheral nerve injury causes abnormal sensory processing, possibly due in part to neuroplastic changes in the CNS. Following chronic constriction injury of the sciatic nerve, transsynaptic degeneration is suggested by the presence of “dark neurons” found in superficial laminae of spinal cord. Previous studies in our laboratory have shown that grafts of adrenal medullary cells into the spinal subarachnoid space can reduce abnormal pain due to peripheral nerve injury. A possible mechanism 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 medullary or control striated muscle tissue implanted in the lumbar subarachnoid space. Control striated muscle-transplanted animals with nerve injury displayed thermal hyperalgesia and elevated numbers of dark neurons in the superficial dorsal horn, compared to intact animals. These dark neurons were increased bilaterally, but predominantly ipsilaterally, to nerve injury. In contrast, in animals with adrenal medullary transplants, reduced numbers of dark neurons were found in parallel with reduced hyperalgesia. The low numbers of dark neurons in these animals were similar to age-matched unoperated controls. Two months after nerve ligation, dark neurons were not found in animals with nerve injury, 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 medullary transplants can attenuate the neuropathological events perpetuating nerve-injury-induced pain by enhancing recovery of spinal neurons from excitotoxic insult.