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.

Abstract:

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

journal_name

Anesth Analg

journal_title

Anesthesia and analgesia

authors

Xu L,Huang Y,Yu X,Yue J,Yang N,Zuo P

doi

10.1213/01.ane.0000287660.29297.7b

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

1838-44, table of contents

issue

6

eissn

0003-2999

issn

1526-7598

pii

105/6/1838

journal_volume

105

pub_type

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