Décosterd I, Buchser E, Gilliard N, Saydoff J, Zurn A D, Aebischer P
Gene Therapy Center and Surgical Research Division, Centre Hospitalier Universitaire Vaudois, Lausanne University Medical School, Switzerland.
Pain. 1998 May;76(1-2):159-66. doi: 10.1016/s0304-3959(98)00044-x.
Intrathecal implants of adrenal chromaffin cells are known to release analgesic substances such as catecholamines and opioid peptides. In the present study, bovine chromaffin cells were encapsulated in a permselective polymer membrane which protects the cells from the host immune system and allows grafting of xenogeneic cells without immunosuppression. The effects of such implants were evaluated on the pain behavior resulting from a chronic constrictive injury (CCI) of the rat sciatic nerve. Sprague-Dawley rats with a unilateral lesion were implanted in the lumbar subarachnoid space and tested for mechanical/thermal allodynia and hyperalgesia. A significant reduction in pain was observed after mechanical non-nociceptive stimulation in animals implanted with chromaffin cells. Furthermore, these animals showed decreased signs of spontaneous pain. However, response to thermal non-noxious stimuli or to painful mechanical stimuli was not significantly decreased. Abundant clusters of viable chromaffin cells intensely labeled with the anti-tyrosine hydroxylase antibodies were observed in the retrieved implants. These results establish the analgesic efficacy of intrathecal encapsulated chromaffin cells in a chronic pain model of nerve injury. Immunoprotected allo- or xenogeneic chromaffin cells acting as 'mini pumps' continuously delivering neuroactive substances could be a useful therapy for patients suffering from neuropathic pain.
已知肾上腺嗜铬细胞鞘内植入物会释放诸如儿茶酚胺和阿片肽等镇痛物质。在本研究中，牛嗜铬细胞被包裹在一种选择透过性聚合物膜中，该膜可保护细胞免受宿主免疫系统的影响，并允许在不进行免疫抑制的情况下移植异种细胞。评估了此类植入物对大鼠坐骨神经慢性压迫性损伤（CCI）所致疼痛行为的影响。对单侧损伤的Sprague-Dawley大鼠进行腰蛛网膜下腔植入，并测试其机械性/热性异常性疼痛和痛觉过敏。在植入嗜铬细胞的动物中，机械性非伤害性刺激后观察到疼痛明显减轻。此外，这些动物的自发疼痛迹象有所减少。然而，对热非有害刺激或疼痛性机械刺激的反应并未显著降低。在回收的植入物中观察到大量用抗酪氨酸羟化酶抗体强烈标记的存活嗜铬细胞簇。这些结果证实了鞘内包裹的嗜铬细胞在神经损伤慢性疼痛模型中的镇痛效果。免疫保护的同种或异种嗜铬细胞作为持续输送神经活性物质的“微型泵”，可能是治疗神经性疼痛患者的一种有效疗法。
