Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury
Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury
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DOI：
10.1523/jneurosci.3715-07.2007
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发表时间：
2007-11-28
影响因子：
5.3
通讯作者：
Heinricher, Mary M.
中科院分区：
文献类型：
--
作者：
Carlson, Jonathan D.;Maire, Jennifer J.;Heinricher, Mary M.
神经损伤可导致人类和动物模型中的机械超敏反应，使得无害的触摸产生疼痛。最近的功能研究表明，在神经病理性疼痛中，延髓头端腹内侧（RVM）的下行疼痛促进作用至关重要，但RVM内相关神经元的潜在机制和特性基本上是未知的。因此，我们的特点是机械反应的生理特征的神经元在RVM脊神经结扎后，神经性疼痛的模型，产生强大的机械痛觉过敏和异常性疼痛。在脊神经结扎后7-14天研究RVM神经元，并使用与热诱发反射相关的放电变化的标准标准将其分类为“开启细胞”、“关闭细胞”或“中性细胞”.已知上细胞促进伤害感受，而下细胞抑制伤害感受，然而中性细胞在疼痛调制中的作用仍然是一个悬而未决的问题。使用校准的von Frey细丝（4 - 100 g）测试对无害和有害机械刺激的神经元和行为反应，所述细丝施加到损伤同侧和对侧的后爪，以及在假手术和未手术的对照动物中.在神经损伤的动物中记录的开细胞和关细胞对无害的机械刺激表现出新的反应，对有害的机械刺激表现出增强的反应。RVM中的神经元超敏反应与行为超敏反应相关。神经损伤后中性细胞对皮肤刺激无反应。这些数据表明，在神经损伤后，RVM中的开细胞和关细胞对无害和有害的机械刺激都是敏感的。这种致敏可能导致神经性疼痛状态的异常性疼痛和痛觉过敏。
Nerve injury can lead to mechanical hypersensitivity in both humans and animal models, such that innocuous touch produces pain. Recent functional studies have demonstrated a critical role for descending pain- facilitating influences from the rostral ventromedial medulla ( RVM) in neuropathic pain, but the underlying mechanisms and properties of the relevant neurons within the RVM are essentially unknown. We therefore characterized mechanical responsiveness of physiologically characterized neurons in the RVM after spinal nerve ligation, a model of neuropathic pain that produces robust mechanical hyperalgesia and allodynia. RVM neurons were studied 7-14 d after spinal nerve ligation, and classified as "on- cells," " off- cells," or " neutral cells" using standard criteria of changes in firing associated with heat- evoked reflexes. On- cells are known to promote nociception, and off- cells to suppress nociception, whereas the role of neutral cells in pain modulation remains an open question. Neuronal and behavioral responses to innocuous and noxious mechanical stimulation were tested using calibrated von Frey filaments ( 4 - 100 g) applied to the hindpaws ipsilateral and contralateral to the injury, and in sham- operated and unoperated control animals. On- and off- cells recorded in nerve- injured animals exhibited novel responses to innocuous mechanical stimulation, and enhanced responses to noxious mechanical stimulation. Neuronal hypersensitivity in the RVM was correlated with behavioral hypersensitivity. Neutral cells remained unresponsive to cutaneous stimulation after nerve injury. These data demonstrate that both on- and off- cells in the RVM are sensitized to innocuous and noxious mechanical stimuli after nerve injury. This sensitization likely contributes to allodynia and hyperalgesia of neuropathic pain states.