The role of tumor necrosis factor-alpha in the neuropathic pain induced by Lumbar 5 ventral root transection in rat.
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.
Xu
Ji-Tian
JT
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.
Xin
Wen-Jun
WJ
Zang
Ying
Y
Wu
Chang-You
CY
Liu
Xian-Guo
XG