Alterations in Endogenous Brain β-Endorphin Release by Adrenal Medullary Transplants in the Spinal Cord

Abstract

While transplants of adrenal medullary cells into the spinal subarachnoid space may produce antinociception via inhibition of spinal pain transmission pathways, alterations at higher central nervous system (CNS) centers have not been addressed. Recent findings suggest that prolonged noxious stimulation results in release of endogenous β-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 subarachnoid space alter endogenous β-endorphin secretion in the hypothalamic arcuate nucleus, its principal CNS source. Pain behaviors and arcuate β-endorphin secretion by microdialysis were monitored during the formalin pain test in animals with spinal adrenal medullary or control transplants. Basal levels of extracellular β-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 β-endorphin release 30–60 min following injection. In contrast, pain behaviors were attenuated and the formalin-induced increase in β-endorphin was completely blocked in adrenal medullary implanted animals. Findings from these studies indicate that adrenal medullary transplants in the spinal subarachnoid space can alter β-endorphin release in the arcuate nucleus both basally and in response to noxious stimuli. Thus, spinally placed adrenal medullary transplants not only alter local spinal cord pharmacology, but can alter endogenous neurochemistry at higher pain processing centers as well.