Role of bovine adrenal medulla 22 (BAM22) in the pathogenesis of neuropathic pain in rats with spinal nerve ligation
Role of bovine adrenal medulla 22 (BAM22) in the pathogenesis of neuropathic pain in rats with spinal nerve ligation
复制标题
牛肾上腺髓质22（BAM22）在脊髓神经结扎大鼠神经病理性疼痛发病机制中的作用
DOI：
10.1016/j.ejphar.2012.04.002
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发表时间：
2012-06-15
影响因子：
5
通讯作者：
Hong, Yanguo
中科院分区：
文献类型：
--
作者：
Chen, Tingjun;Jiang, Jianping;Hong, Yanguo
阿片肽牛肾上腺髓质22 （BAM22）是proenkephalin的裂解产物，已被证明与炎症性疼痛和吗啡耐受有关。本研究旨在探讨BAM22在神经性疼痛中的作用。与假大鼠相比，L5脊髓神经结扎（SNL）显著降低了小尺寸神经元bam22的免疫反应性，并减少了损伤L5背根神经节（DRG）中IB4的结合。双标记研究表明，SNL后邻近完整L4和L6 DRGs的IB4神经元主要表达bam22免疫反应性降低。神经损伤显著增加后爪对机械刺激的敏感性。在snl后第10天鞘内给药BAM22以剂量依赖的方式（3-30 nmol）减轻了机械异常性疼痛，效果持续长达90分钟。用吗啡进行类似治疗，剂量为30nmol，对疼痛超敏反应产生了轻微而短暂的抑制作用。此外，30 nmol的BAM22可抑制snl诱导的脊髓背角白细胞介素-1 β (IL-1 β)的上调。本研究提示，损伤及相邻DRGs小尺寸神经元BAM22表达减少可能是由于脊髓背角IL-1 β上调抑制丧失导致周围神经损伤的疼痛超敏反应。我们的研究结果支持这样的假设，即抗感觉活性的降低失去了对前感觉介质活性的对抗作用，增强了周围神经损伤后的疼痛超敏反应。(C) 2012 Elsevier B.V.版权所有
The opioid peptide bovine adrenal medulla 22 (BAM22) is a cleavage product of proenkephalin and has been shown to be involved in inflammatory pain and morphine tolerance. This study was designed to investigate a role of BAM22 in neuropathic pain. L5 spinal nerve ligation (SNL) significantly reduced BAM22-immunoreactivity in small-sized neurons and depleted IB4 binding in injured L5 dorsal root ganglia (DRG) compared to sham rats. Double labeling study showed that the expression of BAM22-immunoreactivity was decreased mainly in IB4 neurons in the neighboring intact L4 and L6 DRGs following SNL. The nerve injury dramatically increased sensitivity of hindpaw to mechanical stimulation. Intrathecal (i.t.) administration of BAM22 on day 10 post-SNL attenuated mechanical allodynia in a dose-dependent manner (3-30 nmol) and the effect lasted for up to 90 min. Similar treatment with morphine at a dose of 30 nmol produced a mild and brief inhibition on pain hypersensitivity. Furthermore, i.t. administration of 30 nmol of BAM22 suppressed SNL-induced upregulation of interleukin-1 beta (IL-1 beta) in the spinal dorsal horn. The present study suggests that the reduction of BAM22 expression in small-sized neurons in both injured and the adjacent DRGs may contribute to pain hypersensitivity in peripheral nerve injury as a result of loss of inhibition of IL-1 beta upregulation in the spinal dorsal horn. Our results support the hypothesis that a reduction of antinociceptive activity loses the counteraction against activity of pronociceptive mediators, enhancing pain hypersensitivity following peripheral nerve injury. (C) 2012 Elsevier B.V. All rights reserved.