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: Qian Zhang, Jing Yu, Jing Wang, Cui-Ping Ding, Shui-Ping Han, Xiao-Yan Zeng, Jun-Yang Wang
• Journal: Neurochemical research (Neurochem Res) Vol. 40 Issue 7 Pg. 1360-71 (Jul 2015) ISSN: 1573-6903 [Electronic] United States
• PMID: 25952358 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tumor Necrosis Factor-alpha
• Protein Kinases

Topics

• Animals
• Enzyme Activation
• Neuralgia (metabolism, physiopathology)
• Protein Kinases (metabolism)
• Rats
• Red Nucleus (metabolism)
• Signal Transduction
• Tumor Necrosis Factor-alpha (metabolism, physiology)