Alterations in endogenous brain beta-endorphin release by adrenal medullary transplants in the spinal cord

While transplants of adrenal medullary cells into the spinal subarachnoid s pace may produce antinociception via inhibition of spiral pain transmission pathways, alterations at higher central nervous system (CNS) centers have not been addressed. Recent findings suggest that prolonged noxious stimulat ion results in release of endogenous beta -endorphin in the brain, possibly as a compensatory mechanism to reduce nociception. The goal of this study was to determine whether adrenal medullary transplants in the spinal subara chnoid space alter endogenous beta -endorphin secretion in the hypothalamic arcuate nucleus, its principal CNS source. Pain behaviors and arcuate beta -endorphin secretion by microdialysis were monitored during the formalin p ain test in animals with spinal adrenal medullary or control transplants. B asal levels of extracellular beta -endorphin were 3-fold higher in adrenal medullary-implanted than in controls. In control animals, formalin induced robust pain behaviors and a marked transient increase in beta -endorphin re lease 30-60 min following injection. In contrast, pain behaviors were atten uated and the formalin-induced increase in beta -endorphin was completely b locked in adrenal medullary implanted animals. Findings from these studies indicate that adrenal medullary transplants in the spinal subarachnoid spac e can alter beta -endorphin release in the arcuate nucleus both basally and in response to noxious stimuli. Thus, spinally placed adrenal medullary tr ansplants not only alter local spinal cord pharmacology, but can alter endo genous neurochemistry at higher pain processing centers as well. (C) 2000 A merican College of Neuropsychopharmacology. Published by Elsevier Science I nc.