Reduced hyperalgesia in nerve-injured WLD mice: Relationship to nerve fiber phagocytosis, axonal degeneration, and regeneration in normal mice
Reduced hyperalgesia in nerve-injured WLD mice: Relationship to nerve fiber phagocytosis, axonal degeneration, and regeneration in normal mice
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DOI：
10.1006/exnr.1996.0142
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发表时间：
1996-09-01
影响因子：
5.3
通讯作者：
Rodriguez, M
中科院分区：
文献类型：
--
作者：
Myers, RR;Heckman, HM;Rodriguez, M
神经性疼痛状态的发病机制受到与神经损伤相关的炎症因子的影响，并可能部分由巨噬细胞依赖的沃勒氏变性过程介导，巨噬细胞在沃勒氏（轴突）变性中起主导作用，这是神经病慢性收缩损伤模型的疼痛特征，通过在神经损伤部位释放促炎细胞因子。这些细胞因子直接影响神经系统的结构完整性，并与痛觉过敏状态的发展有关。我们假设干扰沃勒氏变性的病理过程会改变神经性疼痛状态的发展。为了验证这一假设，我们研究了神经病变慢性收缩损伤模型中热痛觉过敏的发展，使用正常小鼠和WLD品系小鼠，其中巨噬细胞向神经损伤部位和沃勒氏变性的募集被延迟，我们比较了痛觉过敏的发生和程度与神经损伤的定量测量，包括与沃勒氏变性相关的吞噬细胞活性。在C57BL/6J （6J）小鼠中，痛觉过敏在结扎后3-10天达到高峰，与先前报道的大鼠反应在质量上一致。在C57BL/WLD （WLD）小鼠中，痛觉过敏的减轻与损伤神经中吞噬细胞数量的减少暂时相关，在损伤的WLD神经中，与类似损伤的6J神经相比，轴突变性率降低，WLD动物的再生相应延迟。研究结果表明，沃勒氏变性过程是痛觉过敏发生的关键因素，神经性疼痛小鼠模型的持续发展对探索神经性疼痛的分子基础具有重要意义，干扰沃勒氏变性的细胞介质可能是一种有效的治疗策略，可以调节神经损伤后痛觉过敏的发生和程度。(C) 1996学术出版社，Inc.
The pathogenesis of neuropathic pain states is influenced by inflammatory factors associated with nerve injuries and may be mediated in part by the macrophage-dependent process of Wallerian degeneration, Macrophages play a dominant role in the Wallerian (axonal) degeneration that characterizes the painful chronic constriction injury model of neuropathy by liberating proinflammatory cytokines at the site of nerve injury, These cytokines directly affect the structural integrity of neural systems and have been implicated in the development of hyperalgesic states, We hypothesized that interference with the pathologic process of Wallerian degeneration would alter the development of the neuropathic pain state, To test this hypothesis, we studied the development of thermal hyperalgesia in the chromic constriction injury model of neuropathy using normal mice and mice of the WLD strain in which recruitment of macrophages to the site of nerve injury and Wallerian degeneration are delayed, We compared the onset and magnitude of the hyperalgesia with quantitative measures of nerve injury including the phagocytic cellular activity associated with Wallerian degeneration. In C57BL/6J (6J) mice, hyperalgesia peaked 3-10 days after placement of the ligatures, qualitatively matching the response previously reported for rats, In C57BL/WLD (WLD) mice, there was reduced hyperalgesia temporally associated with reduced numbers of phagocytic cells in the injured nerve, In injured WLD nerves there was a reduced rate of axonal degeneration compared to similarly injured 6J nerves, Regeneration was correspondingly delayed in the WLD animals, The results suggest that the process of Wallerian degeneration is a key factor in the pathogenesis of hyperalgesia, Continued development of mouse models of neuropathic pain nili be important in exploring the molecular basis of neuropathic pain, Interference with the cellular mediators of Wallerian degeneration may be a useful therapeutic strategy that might modulate the onset and magnitude of hyperalgesia following nerve injury. (C) 1996 Academic Press, Inc.