• Li Xu, Yuguang Huang, Xuerong Yu, Jianying Yue, Nan Yang, and Pingping Zuo.
• Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
• Anesth. Analg. 2007 Dec 1;105(6):1838-44, table of contents.

BackgroundTumor necrosis factor alpha (TNF-alpha) could trigger p38 mitogen-activated protein kinase (MAPK) activation. Conversely phosphorylated p38 (p-p38) could induce the upregulation of TNF-alpha. In this study, we examined the hypothesis that chronic constrictive injury (CCI) of the sciatic nerve could promote spinal cord release of TNF-alpha and produce allodynia via the p38 MAPK pathway.MethodsSprague-Dawley rats were divided into five groups: 1) naïve control rats, 2) sham surgery rats, 3) CCI surgery rats without treatment, 4) CCI surgery rats with saline (0.9%) treatment, and 5) CCI surgery rats with the p38 MAPK inhibitor SB203580 treatment. In treatment groups, saline or SB203580 (2 microg, twice a day) was given intrathecally starting 1 day before or 1 day or 7 days after CCI. All rats were killed at different times after surgery to examine p38 MAPK activity and TNF-alpha levels in the spinal cord by Western blot analysis or immunohistochemistry. Mechanical allodynia was tested by a series of von Frey hairs 3, 7, and 14 days after surgery.Resultsp-p38 MAPK was significantly increased at 3, 7, and 14 days after CCI surgery compared with time-matched shams (P < 0.05). Peripheral nerve injury induced mechanical allodynia and enhanced spinal concentrations of TNF-alpha (P < 0.05). Pretreatment or early treatment with SB203580 inhibited p38 MAPK activity, resulting in reduction of TNF-alpha synthesis and attenuation of mechanical allodynia (P < 0.05).Conclusionp38 MAPK activation is one aspect of the signaling cascade that culminates in TNF-alpha synthesis and contributes to mechanical allodynia after peripheral nerve injury.

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