Xu Ji-Tian, Xin Wen-Jun, Zang Ying, Wu Chang-You, Liu Xian-Guo
Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, P.R. China Department of Immunology, Zhongshan Medical School of Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, P.R. China Pain Research Center of Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, P.R. China.
Pain. 2006 Aug;123(3):306-321. doi: 10.1016/j.pain.2006.03.011. Epub 2006 May 3.
Accumulating evidence has demonstrated that tumor necrosis factor-alpha (TNF-alpha) plays an important role in neuropathic pain. Recently, it has been shown that Lumbar 5 ventral root transection (L5 VRT) induces persistent mechanical allodynia and thermal hyperalgesia in bilateral hind paws. In the present study, the role of TNF-alpha in the L5 VRT model was investigated. We found that immunoreactivity (IR) of TNF-alpha and TNF receptor 1 (TNFR1) in ipsilateral (but not in contralateral) L4 and L5 dorsal root ganglion (DRG) was increased following L5 VRT, started 1 day after the lesion and persisted for 2 weeks. Double immunofluorescence staining revealed that the increased TNF-alpha-IR in DRG was in satellite glial cells, immune cells and neuronal cells, while TNFR1-IR was almost restricted at DRG neuronal cells. L5 VRT increased TNF-alpha-IR and TNFR1-IR in bilateral L5 spinal dorsal horn, started 1 day after lesion and persisted for 2 weeks. The increased TNF-alpha-IR in spinal dorsal horn was observed in astrocytes, microglias and neurons, but the upregulation of TNFR1 was mainly in neurons. Intraperitoneal injection of thalidomide, an inhibitor of TNF-alpha synthesis, started at 2h before surgery, blocked mechanical allodynia and thermal hyperalgesia. However, the drug failed to reverse the abnormal pain behaviors, when it was applied at day 7 after surgery. These data suggest that the upregulation of TNF-alpha and TNFR1 in DRG and spinal dorsal horn is essential for the initiation but not for maintenance of the neuropathic pain induced by L5 VRT.
越来越多的证据表明，肿瘤坏死因子-α（TNF-α）在神经性疼痛中起重要作用。最近，研究表明，腰5腹侧神经根横断术（L5 VRT）可诱导双侧后爪出现持续性机械性异常性疼痛和热痛觉过敏。在本研究中，我们调查了TNF-α在L5 VRT模型中的作用。我们发现，L5 VRT后，同侧（而非对侧）L4和L5背根神经节（DRG）中TNF-α和TNF受体1（TNFR1）的免疫反应性（IR）增加，在损伤后1天开始，持续2周。双重免疫荧光染色显示，DRG中TNF-α-IR增加的细胞为卫星神经胶质细胞、免疫细胞和神经元细胞，而TNFR1-IR几乎仅局限于DRG神经元细胞。L5 VRT使双侧L5脊髓背角的TNF-α-IR和TNFR1-IR增加，在损伤后1天开始，持续2周。脊髓背角中TNF-α-IR增加见于星形胶质细胞、小胶质细胞和神经元，但TNFR1的上调主要见于神经元。在手术前2小时开始腹腔注射沙利度胺（一种TNF-α合成抑制剂），可阻断机械性异常性疼痛和热痛觉过敏。然而，在手术后第7天应用该药物时，未能逆转异常疼痛行为。这些数据表明，DRG和脊髓背角中TNF-α和TNFR1的上调对于L5 VRT诱导的神经性疼痛的起始至关重要，但对其维持并非必需。
