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 endogenousTransplantation of adrenal medullary chromaffin cells in the subarachnoid space of the spinal cord has been shown to reduce pain behaviors in several animal models, including inflammatory pain (Ortega-Alvaro et al. 1997;Sagen et al. 1990;Siegan and Sagen 1997;Vaquero et al. 1991;Wang and Sagen 1995), neuropathic pain (Décosterd et al. 1998;Ginzburg and Seltzer 1990; Sagen 1993, 1994), and central pain models (Brewer and Yezierski 1998;Hains et al. 1998;Yu et al. 1998). This has led to the initiation of clinical trials at several centers, with promising outcomes (Buchser et al. 1996;Burgess et al., 1996;Lazorthes et al. 1995;Winnie et al. 1993). Since chromaffin cells produce and secrete several potential pain-reducing neuroactive substances, including opioid peptides and catecholamines, a possible mechanism for this pain reduction is via inhibition of spinal pain transmission pathways. In support for this, adrenal medullary transplants in the rat lumbar spinal subarachnoid space suppress flinching responses 23 , NO . 6 in the formalin pain model, an effect which is partially reversed by opioid antagonist naloxone or ␣ -adrenergic antagonist phentolamine (Siegan and Sagen 1997).While local spinal actions of cellular implants have been the focus of the majority of previous studies, effects on higher central nervous system (CNS) pain processing centers have been largely ignored. In particular, recent findings by our group have demonstrated markedly increased levels of endogenous ␤ -endorphin secretion in the hypothalamic arcuate nucleus coincident with pain behaviors in response to hindpaw injections of formalin (Zangen et al. 1998). As the arcuate nucleus is the principal source of this potent opioid peptide in the CNS (Bach 1997), this finding may be indicative of a compensatory mechanism in response to prolonged noxious stimuli. In support for this, noxious stimuli or persistent pain have been shown to increase activity in the arcuate nucleus as indicated by increased c-fos (Bullitt 1990;Pan et al. 1994), 2-deoxyglucose (Mao et al. 1993, and blood flow (Morrow et al. 2000) in that region. In addition, intense activation of spinal nociceptive pathways by intrathecal capsaicin results in increased ␤ -endorphin release in brain lateral ventricular perfusates (Bach and Yaksh 1995a).The hypothalamic arcuate nucleus may also play a role in endogenous analgesic responses. For example, this region is activated by analgesic low frequency electroacupuncture (Lee and Beitz 1993;Pan et al. 1994;Takeshige et al. 1992; Wang et al. 1990a,b;Zhang et al. 1996), and local stimulation of the arcuate nucleus or ␤ -endorphin microinjection can reduce pain responses to noxious stimuli (Bach and Yak...

Cortisol and antidepressant effects of yoga

“…AVP is known to cause positive affect. [2021] Finally, yoga may cause activation of prefrontal cortex and enhanced glutamate transmission in the arcuate nucleus of the medial hypothalamus resulting in the release of beta-endorphin[22] – the latter causes anxiolysis,[23] which, in turn, may cause a reduction of cortisol.…”

The effects of Beta-Endorphin: state change modification

“…In 2000, Yadid et al . showed the involvement of central β-END mechanisms and the arcuate nucleus in the observed analgesia, apparently by releasing β-END via the CSF as a transporter of messages [ 411 ]. In another interesting study, Finegold et al .…”

Volume transmission of beta-endorphin via the cerebrospinal fluid; a review

“…Chromaffin adrenal medullary cells produce and secrete several potential pain-reducing substances, including opioid peptides [180,181]. Yadid et al [182] transplanted these cells into the subarachnoid space of the spinal cord of the rat and observed a marked reduction in pain behavior and showed the involvement of the central β-END mechanisms and the ARH in the observed analgesia, apparently via long-distance VT. In an another interesting study [183], genes were transferred into the meninges surrounding the spinal cord, causing pia mater cells to produce β-END.…”