Involvement of substance P and calcitonin gene-related peptide in development and maintenance of neuropathic pain from spinal nerve injury model of rat
Involvement of substance P and calcitonin gene-related peptide in development and maintenance of neuropathic pain from spinal nerve injury model of rat
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DOI：
10.1016/j.neures.2007.03.004
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发表时间：
2007-07-01
影响因子：
2.9
通讯作者：
Kim, Jin-Hyuk
中科院分区：
文献类型：
--
作者：
Lee, Seo Eun;Kim, Jin-Hyuk
最近，有人提出未受伤的初级感觉神经元会导致周围神经损伤引起的神经性疼痛。然而，缺乏正常疼痛传递物质如 P 物质和降钙素基因相关肽（CGRP）在神经性疼痛中的作用的证据。测试了 P 物质和 CGRP 在脊髓神经损伤的神经病理性疼痛模型中是否发挥作用。对雄性大鼠进行 L5 和 L6 脊髓神经切断（SNT），并通过测量缩爪阈值（PWT）来评估机械痛觉过敏。 SNT 导致 PWT 持续下降，这是神经性疼痛的征兆。 SNT前10 min将利多卡因浸泡在脊神经上或鞘内注射，阻断损伤引起的神经元放电，并向大鼠鞘内注射L703，606（NK1受体拮抗剂）和CGRP8-37（CGRP受体拮抗剂），阻断损伤放电引起的脊髓中枢神经末梢释放的P物质和CGRP的作用。与盐水治疗的大鼠相比，利多卡因、L703,606 和 CGRP8-37 的治疗将神经性疼痛的发作延迟了 1-4 天。神经性疼痛建立后，鞘内注射 L703,606 和 CGRP8-37 显着减轻机械痛觉过敏 20 分钟。这些结果表明 P 物质和 CGRP 参与神经性疼痛的发生和维持，并且来自完整感觉神经元中央末端的这些肽有助于维持周围神经损伤引起的神经性疼痛。 (C) 2007 Elsevier Ireland Ltd 和日本神经科学学会。版权所有。
Recently, it has been suggested that uninjured primary sensory neurons contribute to neuropathic pain induced by peripheral nerve injury. However, there is lack of evidences of roles of normal pain transmitting substances such as substance P and calcitonin gene-related peptide (CGRP) in neuropathic pain. Whether substance P and CGRP have a role in spinal nerve-injured neuropathic pain model was tested. Male rats were subjected to L5 and L6 spinal nerve tramsection (SNT), and mechanical hyperalgesia was evaluated by measuring paw withdrawal threshold (PWT). SNT induced a persistent PWT decrease, a sign of neuropathic pain. Lidocaine was soaked on spinal nerves or intrathecally injected 10 min before SNT to block neuronal discharges caused by the injury, and L703,606 (NK1 receptor antagonist) and CGRP8-37 (CGRP receptor antagonist) were intrathecally injected into the rats to block actions of substance P and CGRP released from central nerve terminals in the spinal cord by injury discharges. The treatments with lidocaine, L703,606 and CGRP8-37 delayed the onset of neuropathic pain by 1-4 days, compared with the saline-treated rats. After neuropathic pain was established, intrathecal injections of L703,606 and CGRP8-37 significantly mitigated mechanical hyperalgesia for 20 min. These results suggest that substance P and CGRP are involved in the development and maintenance of neuropathic pain and that these peptides from the central terminals of intact sensory neurons contribute to the maintenance of peripheral nerve injury-induced neuropathic pain. (C) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.