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 JR) of TNF-alpha and TNF receptor I (TNFR I) in ipsilateral (but not in contralateral) L4 and L5 dorsal root ganglion (DRG) was increased following L5 VRT, started I 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 I 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-a synthesis, started at 2 It 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. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.