Hama A T, Sagen J
Department of Anatomy and Cell Biology, University of Illinois at Chicago 60612.
Brain Res. 1994 Jul 18;651(1-2):183-93. doi: 10.1016/0006-8993(94)90696-3.
Recent data have suggested that adrenal medullary tissue allografts in the spinal cord subarachnoid space, by releasing catecholamines and opioid peptides, attenuate responses to various acute noxious stimuli and chronic pain-related behaviors. However, the application of this approach is limited by the low availability of allogeneic donor material. Alternatively, chromaffin cells from xenogeneic sources such as the bovine adrenal medulla are plentiful and simple to extract. The goal of this study was to evaluate the potential for bovine chromaffin cell xenografts in the rat spinal subarachnoid space to alleviate chronic pain. This was assessed in an animal model of neuropathic pain induced by loose ligation of the sciatic nerve, which resulted in allodynia, hyperalgesia, and skin temperature abnormalities. Two weeks after nerve injury, animals were implanted with either isolated bovine chromaffin cells or control bovine adrenal fibroblasts in the spinal subarachnoid space at the level of lumbar enlargement and immunosuppressed with cyclosporine A. In animals with chromaffin cell implants, but not fibroblast implants, both cold allodynia and thermal hyperalgesia were markedly reduced or eliminated as early as 1 week following implantation and hind paw skin temperature asymmetry was also normalized. These beneficial effects were maintained without decrement or apparent tolerance for the 9 week course of the symptomology. The analgesic effects of chromaffin cell grafts were partially attenuated following i.t. injection of naloxone and phentolamine separately and in combination, suggesting involvement of spinal opioid and alpha-adrenergic receptors. Following termination of behavioral studies, immunocytochemical analysis revealed robust survival of chromaffin cells in the implants. These results demonstrate that chromaffin cell xenografts may be effective in alleviating pain of neurogenic origin.
最近的数据表明，脊髓蛛网膜下腔内的肾上腺髓质组织同种异体移植，通过释放儿茶酚胺和阿片肽，可减轻对各种急性伤害性刺激的反应以及与慢性疼痛相关的行为。然而，这种方法的应用受到同种异体供体材料可用性低的限制。另外，来自异种来源（如牛肾上腺髓质）的嗜铬细胞丰富且易于提取。本研究的目的是评估大鼠脊髓蛛网膜下腔内牛嗜铬细胞异种移植减轻慢性疼痛的潜力。这在坐骨神经松结扎诱导的神经性疼痛动物模型中进行评估，该模型导致了异常性疼痛、痛觉过敏和皮肤温度异常。神经损伤两周后，在腰膨大水平的脊髓蛛网膜下腔内给动物植入分离的牛嗜铬细胞或对照牛肾上腺成纤维细胞，并用环孢素A进行免疫抑制。在植入嗜铬细胞的动物中，而非成纤维细胞植入的动物中，早在植入后1周，冷异常性疼痛和热痛觉过敏就明显减轻或消除，后足皮肤温度不对称也恢复正常。这些有益效果在9周的症状过程中得以维持，没有减弱或明显的耐受性。分别及联合鞘内注射纳洛酮和酚妥拉明后，嗜铬细胞移植的镇痛作用部分减弱，提示脊髓阿片受体和α-肾上腺素能受体参与其中。行为学研究结束后，免疫细胞化学分析显示植入物中的嗜铬细胞存活良好。这些结果表明，嗜铬细胞异种移植可能有效减轻神经源性疼痛。
