H2Treatment Attenuated Pain Behavior and Cytokine Release Through the HO-1/CO Pathway in a Rat Model of Neuropathic Pain
H2Treatment Attenuated Pain Behavior and Cytokine Release Through the HO-1/CO Pathway in a Rat Model of Neuropathic Pain
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H(2) 治疗通过 HO-1/CO 途径减轻神经性疼痛大鼠模型的疼痛行为和细胞因子释放
DOI：
10.1007/s10753-015-0161-x
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发表时间：
2015-10-01
期刊：
影响因子：
5.1
通讯作者：
Wang, Guolin
中科院分区：
文献类型：
--
作者：
Chen, Yajun;Chen, Hongguang;Wang, Guolin
神经性疼痛（NP）的特征在于持续性疼痛、触觉异常性疼痛或痛觉过敏。周围神经损伤有助于炎症反应的快速进展，同时产生神经病理性疼痛。氢（H-2）具有抗炎、抗凋亡和抗氧化应激作用。因此，我们假设H-2治疗可以减轻神经病理性疼痛大鼠的异常性疼痛和痛觉过敏行为以及炎症因子的释放。采用大鼠坐骨神经慢性压迫性损伤建立周围神经病理性疼痛模型。H-2在术后第1-7天腹腔注射2次，剂量为10 mL/kg/d。术后1-14 d检测大鼠痛敏和痛觉超敏反应，采用酶联免疫吸附法（ELISA）检测大鼠背根神经节（DRG）和脊髓中促炎因子的含量，并于术后14 d检测大鼠坐骨神经损伤后血红素氧合酶（HO）-1 mRNA和蛋白的表达及活性。在给予Sn（IV）原卟啉IX二盐酸盐（SnPP）-IX、氯化血红素和一氧化碳释放分子（CORM）-2对大鼠慢性压迫性损伤（CCI）后，对上述指标进行评估。我们发现H-2明显抑制神经性疼痛中的痛觉过敏和异常性疼痛，并且还减弱促炎细胞因子TNF-α、IL-1 β和高迁移率族蛋白（HMGB）1。H-2促进疼痛过程中HO-1 mRNA和蛋白的表达及活性。SnPP-IX逆转H-2对痛觉过敏和异常性疼痛以及对DRG和脊髓中促炎细胞因子的抑制作用。H-2的镇痛抗炎作用与HO-1/CO信号通路的激活有关。
Neuropathic pain (NP) is characterized by persistent pain, tactile allodynia, or hyperalgesia. Peripheral nerve injury contributes to rapid progress of inflammatory response and simultaneously generates neuropathic pain. Hydrogen (H-2) has anti-inflammation, anti-apoptosis, and anti-oxidative stress effects. Therefore, we hypothesized that H-2 treatment could alleviate allodynic and hyperalgesic behaviors and the release of inflammatory factors in rats with neuropathic pain. Peripheral neuropathic pain was established by chronic constriction injury of sciatic nerve in rats. H-2 was given twice through intraperitoneal injection at a daily dose of 10 mL/kg during days 1-7 after the operation. Hyperalgesia and allodynia were tested, pro-inflammatory factors of dorsal root ganglia (DRG) and the spinal cord were measured by enzyme-linked immunosorbent assay (ELISA) during days 1-14 after the operation, and heme oxygenase (HO)-1 messenger RNA (mRNA) and protein expression and activities were measured at day 14 after sciatic nerve injury in rats. After Sn (IV) protoporphyrin IX dihydrochloride (SnPP)-IX, hemin, and carbon monoxide-releasing molecule (CORM)-2 had been given for chronic constriction injury (CCI) in rats, the above indicators were assessed. We found that H-2 clearly inhibited hyperalgesia and allodynia in neuropathic pain and also attenuated the pro-inflammatory cytokines TNF-alpha, IL-1 beta, and high-mobility group box (HMGB) 1. H-2 improved HO-1 mRNA and protein expression and activities in the process of pain. SnPP-IX reversed the inhibitory effect of H-2 on hyperalgesia and allodynia and on pro-inflammatory cytokines in DRG and the spinal cord. The antinociceptive and anti-inflammatory effects of H-2 were involved in the activation of HO-1/CO signaling during neuropathic pain in rats.