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ANALGESIA

The Influence of p38 Mitogen-Activated Protein Kinase Inhibitor on Synthesis of Inflammatory Cytokine Tumor Necrosis Factor Alpha in Spinal Cord of Rats with Chronic Constriction Injury

Li Xu, MD^*, Yuguang Huang, MD^*, Xuerong Yu, MD^*, Jianying Yue, MD, Nan Yang, PhD, and Pingping Zuo, PhD

From the *Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; Department of Anesthesiology, Tong Ren Hospital, Capital University of Medical Science, Beijing, People’s Republic of China; and Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China.

Address correspondence and reprint requests to Yuguang Huang, Department of Anesthesiology, Peking Union Medical College Hospital, Shuai Fu Yuan 1, Dong Dan district, Beijing, People’s Republic of China 100730. Address e-mail to pumchhyg{at}yahoo.com.cn.

Abstract

BACKGROUND: Tumor necrosis factor (TNF-) could trigger p38 mitogen-activated protein kinase (MAPK) activation. Conversely phosphorylated p38 (p-p38) could induce the upregulation of TNF-. In this study, we examined the hypothesis that chronic constrictive injury (CCI) of the sciatic nerve could promote spinal cord release of TNF- and produce allodynia via the p38 MAPK pathway.

METHODS: Sprague–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 µg, 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- 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.

RESULTS: p-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- (P < 0.05). Pretreatment or early treatment with SB203580 inhibited p38 MAPK activity, resulting in reduction of TNF- synthesis and attenuation of mechanical allodynia (P < 0.05).

CONCLUSION: p38 MAPK activation is one aspect of the signaling cascade that culminates in TNF- synthesis and contributes to mechanical allodynia after peripheral nerve injury.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999