title: The Red Nucleus TNF-α Participates in the Initiation and Maintenance of Neuropathic Pain Through Different Signaling Pathways.
abstract: Previous studies have demonstrated that tumor necrosis factor-alpha (TNF-α) in the red nucleus (RN) plays a facilitated role in the development of neuropathic pain. Here, we further investigated the expression changes and roles of the downstream signaling molecules of the red nucleus TNF-α, including nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), in the initiation and maintenance of neuropathic pain induced by spared nerve injury (SNI). Immunohistochemistry demonstrated that increased expressions of NF-κB, phospho-ERK (p-ERK) and p-p38 MAPK were observed in the RN contralateral (but not ipsilateral) to the nerve injury side at 3 days after SNI compared with sham-operated and normal rats, the up-regulations of NF-κB and p-ERK but not p-p38 MAPK remained at high levels till 14 days later. An elevated expression of p-JNK occurred at 14 days (but not 3 and 7 days) after SNI, which was later than those of NF-κB, p-ERK and p-p38 MAPK. The up-regulations of NF-κB, p-ERK, p-p38 MAPK and p-JNK all could be abolished by microinjection of anti-TNF-α antibody into the RN of rats with SNI. Microinjection of NF-κB inhibitor PDTC, ERK inhibitor PD98059, p38 MAPK inhibitor SB203580 but not JNK inhibitor SP600125 into the RN contralateral to the nerve injury side at 3 days postinjury significantly alleviated SNI-induced mechanical allodynia. In addition, microinjection of PDTC, PD98059 and SP600125 but not SB203580 into the RN at 14 days postinjury significantly alleviated SNI-induced mechanical allodynia. These results suggest that the red nucleus TNF-α produces the algesic effect through activating NF-κB, ERK and p38 MAPK in the early initiation stage but relying on the activation of NF-κB, ERK and JNK in the later maintenance stage of SNI-induced neuropathic pain.
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Cui-Ping
authors.initials: CP
authors.lastname: Ding
authors.forename: Shui-Ping
authors.initials: SP
authors.lastname: Han
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zeng
authors.forename: Jun-Yang
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D009437:Neuralgia / Q000378:metabolism / Q000503:physiopathology*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D012012:Red Nucleus / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D011494:Protein Kinases