Deep tissue inflammation upregulates neuropeptides and evokes nociceptive behaviors which are modulated by a neuropeptide antagonist
Deep tissue inflammation upregulates neuropeptides and evokes nociceptive behaviors which are modulated by a neuropeptide antagonist
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DOI：
10.1016/j.pain.2005.10.003
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发表时间：
2006-01-01
期刊：
影响因子：
7.4
通讯作者：
Dessem, D
中科院分区：
文献类型：
--
作者：
Ambalavanar, R;Moritani, M;Dessem, D
神经肽拮抗剂的治疗价值的最新进展为理解神经肽在伤害感受和炎症中的功能作用带来了新的重要性。为了探索这种关系，我们检查了深部组织炎症后的行为变化和初级传入神经元可塑性。颅面肌肉炎症后一小时，同侧和对侧头部缩回阈值以及同侧和对侧后爪缩回阈值降低，并保持降低28天。三叉神经节内降钙素基因相关肽（CGRP）水平升高与这种机械性异常性疼痛暂时相关。炎症还导致支配发炎肌肉的 CGRP 和 P 物质 (SP) 免疫阳性三叉神经节神经元数量增加，但并未引起肽能肌肉传入神经元大小分布的变化。位于中脑三叉神经核脑干内的三叉神经本体感觉肌传入神经元在炎症之前或之后不表达 CGRP 或 SP。在佐剂注射前两分钟静脉注射 CGRP 受体拮抗剂 (8-37) 可阻止血浆外渗并消除头部和后肢机械异常性疼痛。在 CFA 之前将 CGRP 拮抗剂直接局部注射到咬肌中，产生类似但不太明显的效果。这些发现表明，单侧颅面肌炎症会在远处产生机械性异常性疼痛，并上调支配深层组织的初级传入神经元中的 CGRP 和 SP。这些数据进一步表明 CGRP 和 SP 参与深部组织伤害感受机制，并表明肽拮抗剂可能具有治疗肌肉骨骼疼痛的潜力。 (c) 2006 年国际疼痛研究协会。由 Elsevier B.V. 出版。保留所有权利。
Promising recent developments in the therapeutic value of neuropeptide antagonists have generated renewed importance in understanding the functional role of neuropeptides in nociception and inflammation. To explore this relationship we examined behavioral changes and primary afferent neuronal plasticity following deep tissue inflammation. One hour following craniofacial muscle inflammation ipsilateral as well as contralateral head withdrawal thresholds and ipsi- and contralateral hindpaw withdrawal thresholds were lowered and remained reduced for 28 days. Elevated levels of calcitonin gene-related peptide (CGRP) within the trigeminal ganglion temporally correlated with this mechanical allodynia. Inflammation also induced an increase in the number of CGRP and substance P (SP)-immunopositive trigeminal ganglion neurons innervating inflamed muscle but did not evoke a shift in the size distribution of peptidergic muscle afferent neurons. Trigeminal proprioceptive muscle afferent neurons situated within the brainstem in the mesencephalic trigeminal nucleus did not express CGRP or SP prior to or following, inflammation. Intravenous administration of CGRP receptor antagonist (8-37) two minutes prior to adjuvant injection blocked plasma extravasation and abolished both head and hindlimb mechanical allodynia. Local injection of CGRP antagonist directly into the masseter muscle prior to CFA produced similar, but less pronounced, effects. These findings indicate that unilateral craniofacial muscle inflammation produces mechanical allodynia at distant sites and upregulates CGRP and SP in primary afferent neurons innervating deep tissues. These data further implicate CGRP and SP in deep tissue nociceptive mechanisms and suggest that peptide antagonists may have therapeutic potential for musculoskeletal pain. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.