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NF-κB, ERK, p38 MAPK and JNK contribute to the initiation and/or maintenance of mechanical allodynia induced by tumor necrosis factor-alpha in the red nucleus.
Brain Res Bull. 2013 Oct; 99:132-9.BR

Abstract

Previous studies have demonstrated that tumor necrosis factor-alpha (TNF-α) in the red nucleus (RN) plays facilitated roles in the development of abnormal pain. Here, the roles of 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 TNF-α-evoked mechanical allodynia were investigated. Repeated microinjection of recombinant rat TNF-α (20 ng daily for 3 days) into the unilateral RN of normal rats induced a significant mechanical allodynia in the contralateral but not ipsilateral hind paw at the fifth day and disappeared 24h later. Re-injection of a single bolus of 20 ng TNF-α into the same RN reproduced this mechanical allodynia within 30 min, which was used as a pain model for further experiments. Immunohistochemistry demonstrated that NF-κB, phospho-ERK (p-ERK) and p-p38 MAPK in the RN were significantly up-regulated at 1h after TNF-α microinjection, the up-regulations of NF-κB and p-ERK but not p-p38 MAPK remained at high levels till 4h later. A significant up-regulation of p-JNK occurred at 4h (but not 1h) after TNF-α microinjection, which was later than those of NF-κB, p-ERK and p-p38 MAPK. Pre-treatment with NF-κB inhibitor PDTC, ERK inhibitor PD98059 or p38 MAPK inhibitor SB203580 at 30 min before TNF-α microinjected into the RN completely prevented TNF-α-evoked mechanical allodynia. Pre-treatment with JNK inhibitor SP600125 did not prevent but reversed TNF-α-evoked mechanical allodynia during the subsequent detection time. Post-treatment with PDTC, PD98059 or SP600125 (but not SB203580) at 4h after TNF-α microinjected into the RN significantly reversed TNF-α-evoked mechanical allodynia. These results further prove that TNF-α in the RN plays a crucial role in the development of abnormal pain, and the algesic effect of TNF-α is initiated through activating NF-κB, ERK and p38 MAPK. The later maintenance of TNF-α-evoked mechanical allodynia mainly relies on the activation of NF-κB, ERK and JNK, but not p38 MAPK.

Authors+Show Affiliations

Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China; Department of Pathogenic Biology and Immunology, Qinghai University College of Medicine, Xining, Qinghai 810016, China.No 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

24161765

Citation

Zhang, Qian, et al. "NF-κB, ERK, P38 MAPK and JNK Contribute to the Initiation And/or Maintenance of Mechanical Allodynia Induced By Tumor Necrosis Factor-alpha in the Red Nucleus." Brain Research Bulletin, vol. 99, 2013, pp. 132-9.
Zhang Q, Wang J, Duan MT, et al. NF-κB, ERK, p38 MAPK and JNK contribute to the initiation and/or maintenance of mechanical allodynia induced by tumor necrosis factor-alpha in the red nucleus. Brain Res Bull. 2013;99:132-9.
Zhang, Q., Wang, J., Duan, M. T., Han, S. P., Zeng, X. Y., & Wang, J. Y. (2013). NF-κB, ERK, p38 MAPK and JNK contribute to the initiation and/or maintenance of mechanical allodynia induced by tumor necrosis factor-alpha in the red nucleus. Brain Research Bulletin, 99, 132-9. https://doi.org/10.1016/j.brainresbull.2013.10.008
Zhang Q, et al. NF-κB, ERK, P38 MAPK and JNK Contribute to the Initiation And/or Maintenance of Mechanical Allodynia Induced By Tumor Necrosis Factor-alpha in the Red Nucleus. Brain Res Bull. 2013;99:132-9. PubMed PMID: 24161765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NF-κB, ERK, p38 MAPK and JNK contribute to the initiation and/or maintenance of mechanical allodynia induced by tumor necrosis factor-alpha in the red nucleus. AU - Zhang,Qian, AU - Wang,Jing, AU - Duan,Mei-Ting, AU - Han,Shui-Ping, AU - Zeng,Xiao-Yan, AU - Wang,Jun-Yang, Y1 - 2013/10/23/ PY - 2013/05/16/received PY - 2013/09/18/revised PY - 2013/10/16/accepted PY - 2013/10/29/entrez PY - 2013/10/29/pubmed PY - 2014/7/16/medline KW - DRG KW - ERK KW - IL KW - JNK KW - LTP KW - Mitogen-activated protein kinase KW - NF-κB KW - NGF KW - Nuclear factor-kappa B KW - PDTC KW - PWT KW - RN KW - RVM KW - Rat KW - Red nucleus KW - SNI KW - TNF-α KW - Tumor necrosis factor-alpha KW - c-Jun N-terminal kinase KW - dorsal root ganglia KW - extracellular signal-regulated kinase KW - interleukin KW - long-term potentiation KW - nerve growth factor KW - nuclear factor-kappa B KW - p38 MAPK KW - p38 mitogen-activated protein kinase KW - paw withdrawal threshold KW - pyrrolidine dithiocarbamate KW - red nucleus KW - rostral ventromedial medulla KW - spared nerve injury KW - tumor necrosis factor-alpha SP - 132 EP - 9 JF - Brain research bulletin JO - Brain Res Bull VL - 99 N2 - Previous studies have demonstrated that tumor necrosis factor-alpha (TNF-α) in the red nucleus (RN) plays facilitated roles in the development of abnormal pain. Here, the roles of 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 TNF-α-evoked mechanical allodynia were investigated. Repeated microinjection of recombinant rat TNF-α (20 ng daily for 3 days) into the unilateral RN of normal rats induced a significant mechanical allodynia in the contralateral but not ipsilateral hind paw at the fifth day and disappeared 24h later. Re-injection of a single bolus of 20 ng TNF-α into the same RN reproduced this mechanical allodynia within 30 min, which was used as a pain model for further experiments. Immunohistochemistry demonstrated that NF-κB, phospho-ERK (p-ERK) and p-p38 MAPK in the RN were significantly up-regulated at 1h after TNF-α microinjection, the up-regulations of NF-κB and p-ERK but not p-p38 MAPK remained at high levels till 4h later. A significant up-regulation of p-JNK occurred at 4h (but not 1h) after TNF-α microinjection, which was later than those of NF-κB, p-ERK and p-p38 MAPK. Pre-treatment with NF-κB inhibitor PDTC, ERK inhibitor PD98059 or p38 MAPK inhibitor SB203580 at 30 min before TNF-α microinjected into the RN completely prevented TNF-α-evoked mechanical allodynia. Pre-treatment with JNK inhibitor SP600125 did not prevent but reversed TNF-α-evoked mechanical allodynia during the subsequent detection time. Post-treatment with PDTC, PD98059 or SP600125 (but not SB203580) at 4h after TNF-α microinjected into the RN significantly reversed TNF-α-evoked mechanical allodynia. These results further prove that TNF-α in the RN plays a crucial role in the development of abnormal pain, and the algesic effect of TNF-α is initiated through activating NF-κB, ERK and p38 MAPK. The later maintenance of TNF-α-evoked mechanical allodynia mainly relies on the activation of NF-κB, ERK and JNK, but not p38 MAPK. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/24161765/NF_κB_ERK_p38_MAPK_and_JNK_contribute_to_the_initiation_and/or_maintenance_of_mechanical_allodynia_induced_by_tumor_necrosis_factor_alpha_in_the_red_nucleus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(13)00165-2 DB - PRIME DP - Unbound Medicine ER -