Cutaneous tactile allodynia associated with microvascular dysfunction in muscle
Cutaneous tactile allodynia associated with microvascular dysfunction in muscle
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DOI：
10.1186/1744-8069-4-49
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发表时间：
2008-10-28
期刊：
影响因子：
3.3
通讯作者：
Coderre, Terence J.
中科院分区：
文献类型：
--
作者：
Laferriere, Andre;Millecamps, Magali;Coderre, Terence J.
背景资料：皮肤触觉异常性疼痛或对皮肤的机械刺激的疼痛超敏反应通常与神经性疼痛相关，尽管也存在于没有神经损伤证据的慢性疼痛患者中。我们研究是否深层组织微血管功能障碍，慢性非神经性疼痛的一个常见特征，有助于异常性疼痛。结果：持续性皮肤异常性疼痛是在大鼠后爪缺血再灌注损伤，诱导微血管功能障碍，包括动脉血管痉挛和毛细血管慢流/无复流，在肌肉中。微血管功能障碍导致持续性肌肉缺血、表皮内神经纤维减少和与肌肉缺血相关的异常性疼痛，但与皮肤神经丧失无关。受影响的后爪肌肉显示脂质过氧化、核因子κ B上调和促炎细胞因子增强，而异常性疼痛通过抑制这些改变的药物缓解。异常性疼痛增加，沿着与后爪肌肉乳酸，当这些大鼠行使，并减少了酸敏感离子通道antagonistant.Conclusion：我们的研究结果表明，如何微血管功能障碍和缺血在肌肉中可以发挥关键作用，在皮肤异常性疼痛的发展，并鼓励研究这些机制如何有助于慢性疼痛。我们预计，专注于与肌肉微血管功能障碍相关的疼痛机制将为皮肤触觉异常性疼痛的慢性疼痛患者提供新的有效治疗方法。
Background: Cutaneous tactile allodynia, or painful hypersensitivity to mechanical stimulation of the skin, is typically associated with neuropathic pain, although also present in chronic pain patients who do not have evidence of nerve injury. We examine whether deep tissue microvascular dysfunction, a feature common in chronic non-neuropathic pain, contributes to allodynia.Results: Persistent cutaneous allodynia is produced in rats following a hind paw ischemia-reperfusion injury that induces microvascular dysfunction, including arterial vasospasms and capillary slow flow/no-reflow, in muscle. Microvascular dysfunction leads to persistent muscle ischemia, a reduction of intraepidermal nerve fibers, and allodynia correlated with muscle ischemia, but not with skin nerve loss. The affected hind paw muscle shows lipid peroxidation, an upregulation of nuclear factor kappa B, and enhanced pro-inflammatory cytokines, while allodynia is relieved by agents that inhibit these alterations. Allodynia is increased, along with hind paw muscle lactate, when these rats exercise, and is reduced by an acid sensing ion channel antagonist.Conclusion: Our results demonstrate how microvascular dysfunction and ischemia in muscle can play a critical role in the development of cutaneous allodynia, and encourage the study of how these mechanisms contribute to chronic pain. We anticipate that focus on the pain mechanisms associated with microvascular dysfunction in muscle will provide new effective treatments for chronic pain patients with cutaneous tactile allodynia.