Pioglitazone Attenuates Tactile Allodynia and Thermal Hyperalgesia in Mice Subjected to Peripheral Nerve Injury
Pioglitazone Attenuates Tactile Allodynia and Thermal Hyperalgesia in Mice Subjected to Peripheral Nerve Injury
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DOI：
10.1254/jphs.08207fp
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发表时间：
2008-11-01
影响因子：
3.5
通讯作者：
Kishioka, Shiroh
中科院分区：
文献类型：
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作者：
Maeda, Takehiko;Kiguchi, Norikazu;Kishioka, Shiroh
为了阐明过氧化物酶体增殖物激活受体γ（PPARgamma）在神经性疼痛中的作用，我们在神经性疼痛模型中研究了PPARgamma激动剂吡格列酮对触觉异常性疼痛和热痛觉过敏的影响。对小鼠进行部分坐骨神经结扎（PSL）并给予吡格列酮（1-25 mg/kg，p.o.）每天一次。在未处理的小鼠中，PPAR γ分布于脊髓背根神经节和背角的神经元以及坐骨神经外膜的脂肪细胞中。PSL引起触觉异常性疼痛和热痛觉过敏两周。PSL后第一周给予吡格列酮可减轻热痛觉过敏和触觉异常性疼痛，这是剂量依赖性的，并可被GW 9662（2 mg/kg，i. p.）阻断，PPAR γ拮抗剂。吡格列酮给药第二周也缓解了触觉异常性疼痛，但在PSL前一周给药没有效果。在PSL第7天对小鼠单次给予吡格列酮未改变触觉异常性疼痛和热痛觉过敏。PSL诱导的肿瘤坏死因子-α和白细胞介素-6的上调，这是神经性疼痛所必需的，在第一周被吡格列酮抑制。这表明吡格列酮通过减弱PPAR γ刺激引起的促炎细胞因子上调来减轻神经性疼痛。
To clarify the role of peroxisome proliferator activated receptor gamma (PPAR gamma) in neuropathic pain, we examined the effect of pioglitazone, a PPAR gamma agonist, on tactile allodynia and thermal hyperalgesia in a neuropathic pain model. Mice were subjected to partial sciatic nerve ligation (PSL) and given pioglitazone (1-25 mg/kg, p.o.) once daily. PPAR gamma was distributed in the neurons of the dorsal root ganglion and the dorsal horn of the spinal cord and in the adipocytes at the epineurium of the sciatic nerve in naive mice. PSL elicited tactile allodynia and thermal hyperalgesia for two weeks. Administration of pioglitazone for the first week after PSL attenuated thermal hyperalgesia and tactile allodynia, which was dose-dependent and blocked by GW9662 (2 mg/kg, i.p.), a PPAR gamma antagonist. Administration of pioglitazone for the second week also relieved tactile allodynia, but administration one week before PSL had no effect. A single administration of pioglitazone to mice on day 7 of PSL did not alter tactile allodynia and thermal hyperalgesia. PSL-induced upregulation of tumor necrosis factor-alpha and interleukin-6, which are essential for neuropathic pain, was suppressed by pioglitazone for the first week. This suggests that pioglitazone alleviates neuropathic pain through attenuation of proinflammatory cytokine upregulation by PPAR gamma stimulation.