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

Qian Zhang, Jing Wang, Mei-Ting Duan, Shui-Ping Han, Xiao-Yan Zeng, Jun-Yang Wang
Brain Research Bulletin 2013, 99: 132-9
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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"