Spinal leptin contributes to the pathogenesis of neuropathic pain in rodents
Spinal leptin contributes to the pathogenesis of neuropathic pain in rodents
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DOI：
10.1172/jci36785
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发表时间：
2009-02-01
影响因子：
15.9
通讯作者：
Mao, Jianren
中科院分区：
文献类型：
--
作者：
Lim, Grewo;Wang, Shuxing;Mao, Jianren
神经损伤后的疼痛，一种被称为神经性疼痛的现象，是一种使人衰弱的临床病症，但其潜在机制仍不清楚。由于瘦素是一种主要由非神经元组织产生的脂肪细胞因子，与神经元功能的调节有关，我们采用慢性坐骨神经损伤（CCI）大鼠模型研究了瘦素在神经病理性疼痛中的作用。我们报告说，瘦素严重促成CCI后的疼痛行为。具体而言，瘦素拮抗剂的脊髓给药预防和逆转大鼠的神经性疼痛行为。进一步的检查发现，瘦素和瘦素受体（Ob-Rb）的长型水平显着增加同侧脊髓后角周围神经损伤后。机制研究表明，瘦素通过JAK/STAT途径上调脊髓NMDA受体和IL-1 β的表达。此外，这些CCI诱导的行为和细胞反应在瘦素缺乏的小鼠中减少，并通过在幼稚大鼠中脊髓施用外源性瘦素来模仿。我们的研究结果揭示了脊髓瘦素在神经病理性疼痛的发病机制中的关键作用，并表明我们认为是一种新的形式的非神经元和神经元的相互作用的病理性疼痛的机制。
Pain after nerve injury, a phenomenon referred to as neuropathic pain, is a debilitating clinical condition, but the underlying mechanisms remain unclear. As leptin, an adipocytokine produced mainly by nonneuronal tissue, has been implicated in the regulation of neuronal functions, we examined the role of leptin in neuropathic pain using a rat model of the condition chronic constriction sciatic nerve injury (CCI). We report that leptin critically contributed to pain behaviors following CCI. Specifically, spinal administration of a leptin antagonist prevented and reversed neuropathic pain behaviors in rats. Further examination revealed that levels of both leptin and the long form of the leptin receptor (Ob-Rb) were substantially increased within the ipsilateral spinal cord dorsal horn after peripheral nerve injury. Mechanistic studies showed that leptin upregulated the expression of both the spinal NMDA receptor and IL-1 beta through the JAK/STAT pathway. Furthermore, these CCI-induced behavioral and cellular responses were diminished in leptin-deficient mice and mimicked by spinal administration of exogenous leptin in naive rats. Our findings reveal a critical role for spinal leptin in the pathogenesis of neuropathic pain and suggest what we believe to be a novel form of nonneuronal and neuronal interactions in the mechanisms of pathological pain.