Role of histamine H3 and H4 receptors in mechanical hyperalgesia following peripheral nerve injury
Role of histamine H3 and H4 receptors in mechanical hyperalgesia following peripheral nerve injury
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DOI：
10.1159/000125048
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发表时间：
2008-01-01
影响因子：
2.4
通讯作者：
Moalem-Taylor, Gila
中科院分区：
文献类型：
--
作者：
Smith, Fiona M.;Haskelberg, Hila;Moalem-Taylor, Gila
目的：组胺是一种化学介质，作用于四种已知的组胺受体，并在伤害感觉和神经性疼痛的发展中广泛涉及。阻断组胺H-1和H-2受体已被证明可以减轻神经损伤后的痛觉过敏，但组胺H-3和H-4受体在神经性疼痛中的作用尚未被研究。在这里，我们使用组胺H-3和H-4受体阻滞剂来评估它们对周围神经损伤后神经性疼痛行为和肥大细胞数量的影响。此外，我们评估了激活H-4受体对神经性疼痛行为的影响。方法：将大鼠作为神经性疼痛模型的坐骨神经部分结扎，并全身或局部（后肢）使用H-3/H-4受体逆激动剂硫哌丁胺、特异性H-4受体拮抗剂JNJ 7777120或H-4受体激动剂VUF 8430进行治疗。采用Randall-Selitto试验测量机械痛觉过敏1-3周，术后9 h通过组织学分析坐骨神经组织中完整肥大细胞的数量。结果：大鼠经硫哌丁胺或jnj7777120处理后，坐骨神经部分结扎后机械性痛觉过敏明显增强。这些大鼠损伤神经中完整肥大细胞的数量高于对照大鼠，提示肥大细胞脱颗粒减少，但仍显著低于完整神经。用VUF 8430处理的大鼠表现出明显减轻的机械性痛觉过敏。结论：我们提出，硫代丁胺和jnj7777120引起的机械性痛觉过敏的增加和VUF 8430引起的机械性痛觉过敏的减少可能代表这些药物对机械特异性初级传入事件的直接作用，或者这些药物通过损伤诱导的炎症间接作用。版权所有(c) 2008 S. Karger AG，巴塞尔。
Objective: Histamine is a chemical mediator that acts at four known types of histamine receptors and has been widely implicated in the development of nociception and neuropathic pain. Blocking histamine H-1 and H-2 receptors has been shown to reduce hyperalgesia following nerve injury, but the role of histamine H-3 and H-4 receptors in neuropathic pain has not been studied. Here, we used blockers of histamine H-3 and H-4 receptors to assess their effects on neuropathic pain behavior and mast cell numbers following peripheral nerve injury. In addition, we assessed the effect of activating H-4 receptors on neuropathic pain behavior. Methods: Rats were subjected to a partial ligation of the sciatic nerve, a model of neuropathic pain, and were treated either systemically or locally (hindpaw) with the H-3/H-4 receptor inverse agonist thioperamide, the specific H-4 receptor antagonist JNJ 7777120, or the H-4 receptor agonist VUF 8430. Measurements of mechanical hyperalgesia were carried out by Randall-Selitto test for 1-3 weeks, and sciatic nerve tissues were analyzed for numbers of intact mast cells by histology at 9 h after surgery. Results: Rats treated with thioperamide or JNJ 7777120 showed significantly enhanced mechanical hyperalgesia after partial ligation of the sciatic nerve. The number of intact mast cells in the injured nerve of these rats was higher than in control rats suggesting reduced mast cell degranulation, but was still significantly lower than in intact nerves. Rats treated with VUF 8430 showed significantly reduced mechanical hyperalgesia. Conclusion: We propose that the increase in mechanical hyperalgesia produced by thioperamide and JNJ 7777120 and the decrease in mechanical hyperalgesia produced by VUF 8430 may represent a direct effect of these agents on mechanospecific primary afferents, or an indirect effect of these agents via injury-induced inflammation. Copyright (c) 2008 S. Karger AG, Basel.