Sagen J, Wang H
Department of Anatomy and Cell Biology, University of Illinois, Chicago 60612.
Eur J Pharmacol. 1990 Apr 25;179(3):427-33. doi: 10.1016/0014-2999(90)90184-8.
Transplants of adrenal medullary tissue or isolated chromaffin cells into the spinal cord subarachnoid space has been shown to reduce pain sensitivity in rats. This analgesia probably results from the release of neuroactive substances, particularly opioid peptides, from the transplanted cells since it is induced by nicotinic stimulation of chromaffin cell receptors, and can be blocked by naloxone. However, this analgesia is short-lived, most likely due to the rapid hydrolysis of opioid peptides. The purpose of this study was to determine whether protection of opioid peptide hydrolysis by the potent enkephalinase inhibitor kelatorphan could prolong this analgesia. Results indicated that the intrathecal injection of kelatorphan in animals with either adrenal medullary or chromaffin cell implants significantly prolonged nicotine-stimulated analgesia. Pretreatment with naloxone completely eliminated this analgesia. These results suggest that it may be possible to induce long-term reductions in pain sensitivity using enkephalinase inhibitors following the transplantation of opioid peptide-producing cells into the CNS.
将肾上腺髓质组织或分离的嗜铬细胞移植到脊髓蛛网膜下腔已被证明可降低大鼠的疼痛敏感性。这种镇痛作用可能是由于移植细胞释放神经活性物质，特别是阿片肽所致，因为它是由烟碱刺激嗜铬细胞受体诱导产生的，并且可被纳洛酮阻断。然而，这种镇痛作用是短暂的，最可能的原因是阿片肽的快速水解。本研究的目的是确定强效脑啡肽酶抑制剂凯拉托芬对阿片肽水解的保护作用是否能延长这种镇痛时间。结果表明，鞘内注射凯拉托芬可使植入肾上腺髓质或嗜铬细胞的动物的尼古丁刺激镇痛作用显著延长。用纳洛酮预处理可完全消除这种镇痛作用。这些结果表明，在将产生阿片肽的细胞移植到中枢神经系统后，使用脑啡肽酶抑制剂可能诱导疼痛敏感性的长期降低。
