Role of peripheral hyperpolarization-activated cyclic nucleotide-modulated channel pacemaker channels in acute and chronic pain models in the rat
Role of peripheral hyperpolarization-activated cyclic nucleotide-modulated channel pacemaker channels in acute and chronic pain models in the rat
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DOI：
10.1016/j.neuroscience.2006.10.048
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发表时间：
2007-02-23
期刊：
影响因子：
3.3
通讯作者：
Chaplan, S. R.
中科院分区：
文献类型：
--
作者：
Luo, L.;Chang, L.;Chaplan, S. R.
超极化激活，环核苷酸解调（HCN）通道有助于心脏和中枢神经系统的节律性自发活动。异位自发性神经元活动与急性和慢性痛觉过敏、异位性疼痛和自发性疼痛的发生和维持有关。先前，我们记录了全身给药ZD7288，一种特定的起搏器电流阻滞剂（I-h），减少脊神经结扎（SNL）大鼠背根神经节（DRG）的异位活动和逆转触觉异常性痛[Chaplan SR， Guo HQ, Lee DH, Luo L, Liu C, Kuei C, Velumian AA, Butler MP, Brown SM, Dubin AE（2003）神经元超极化激活的起搏器通道导致神经性疼痛。[J].中华神经科学杂志，23(11):1169-1178。自发性疼痛是周围神经损伤的主要临床表现；然而，I-h在自发性疼痛中的作用尚未被描述。在进一步的大鼠研究中，我们报告了全身给药ZD7288可以逆转轻度热损伤（MTI）引起的自发性疼痛和SNL和MTI引起的触觉异常性疼痛。相比之下，ZD7288没有减轻热痛觉过敏。由于足底（局部）给药ZD7288完全抑制了由MTI和SNL引起的触觉异常性痛，并减少了由MTI引起的自发性疼痛，因此一个重要的作用位点似乎在皮肤中。足底皮肤切片免疫组化染色检测到HCN1-HCN4在机械感觉结构（如迈斯纳小体和默克尔细胞）中的表达。总的来说，这些数据表明，I-h在包括特殊感觉结构在内的周围神经系统中的表达和调节可能在感觉加工中发挥重要作用，并有助于自发性疼痛和触觉异常性痛。(c) 2006 IBRO。Elsevier Ltd.出版。版权所有。
Hyperpolarization-activated, cyclic nucleotidemodulated (HCN) channels contribute to rhythmic spontaneous activity in the heart and CNS. Ectopic spontaneous neuronal activity has been implicated in the development and maintenance of acute and chronic hyperalgesia, allodynia and spontaneous pain. Previously, we documented that systemic administration of ZD7288, a specific blocker of pacemaker current (I-h), decreased ectopic activity in dorsal root ganglion (DRG) and reversed tactile allodynia in spinal nerve ligated (SNL) rats [Chaplan SR, Guo HQ, Lee DH, Luo L, Liu C, Kuei C, Velumian AA, Butler MP, Brown SM, Dubin AE (2003) Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain. J Neurosci 23:1169-1178]. Spontaneous pain is the chief clinical manifestation of peripheral nerve injury; however, a role for I-h in spontaneous pain has not been described. Here, in further rat studies, we report that systemic administration of ZD7288 reversed spontaneous pain induced by mild thermal injury (MTI) and tactile allodynia induced by SNL and MTI. In contrast, ZD7288 did not reduce thermal hyperalgesia. An important locus of action appears to be in the skin since intraplantar (local) administration of ZD7288 completely suppressed tactile allodynia arising from MTI and SNL and reduced spontaneous pain due to MTI. Immunohistochemical staining of plantar skin sections detected HCN1-HCN4 expression in mechanosensory structures (e.g., Meissner's corpuscles and Merkel cells). Collectively, these data suggest that expression and modulation of I-h in the peripheral nervous system, including specialized sensory structures, may play a significant role in sensory processing and contribute to spontaneous pain and tactile allodynia. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.