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The Red Nucleus TNF-α Participates in the Initiation and Maintenance of Neuropathic Pain Through Different Signaling Pathways.
Neurochem Res. 2015 Jul; 40(7):1360-71.NR

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+Show Affiliations

Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25952358

Citation

Zhang, Qian, et al. "The Red Nucleus TNF-α Participates in the Initiation and Maintenance of Neuropathic Pain Through Different Signaling Pathways." Neurochemical Research, vol. 40, no. 7, 2015, pp. 1360-71.
Zhang Q, Yu J, Wang J, et al. The Red Nucleus TNF-α Participates in the Initiation and Maintenance of Neuropathic Pain Through Different Signaling Pathways. Neurochem Res. 2015;40(7):1360-71.
Zhang, Q., Yu, J., Wang, J., Ding, C. P., Han, S. P., Zeng, X. Y., & Wang, J. Y. (2015). The Red Nucleus TNF-α Participates in the Initiation and Maintenance of Neuropathic Pain Through Different Signaling Pathways. Neurochemical Research, 40(7), 1360-71. https://doi.org/10.1007/s11064-015-1599-9
Zhang Q, et al. The Red Nucleus TNF-α Participates in the Initiation and Maintenance of Neuropathic Pain Through Different Signaling Pathways. Neurochem Res. 2015;40(7):1360-71. PubMed PMID: 25952358.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Red Nucleus TNF-α Participates in the Initiation and Maintenance of Neuropathic Pain Through Different Signaling Pathways. AU - Zhang,Qian, AU - Yu,Jing, AU - Wang,Jing, AU - Ding,Cui-Ping, AU - Han,Shui-Ping, AU - Zeng,Xiao-Yan, AU - Wang,Jun-Yang, Y1 - 2015/05/08/ PY - 2015/02/09/received PY - 2015/05/02/accepted PY - 2015/04/11/revised PY - 2015/5/9/entrez PY - 2015/5/9/pubmed PY - 2016/4/12/medline SP - 1360 EP - 71 JF - Neurochemical research JO - Neurochem Res VL - 40 IS - 7 N2 - 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. SN - 1573-6903 UR - https://www.unboundmedicine.com/medline/citation/25952358/The_Red_Nucleus_TNF_α_Participates_in_the_Initiation_and_Maintenance_of_Neuropathic_Pain_Through_Different_Signaling_Pathways_ L2 - https://doi.org/10.1007/s11064-015-1599-9 DB - PRIME DP - Unbound Medicine ER -