The Gene Expression of Dynorphin, Enkephalin, c-Fos in the Neuropathic Rat

Han, Neung Hee; Lee, Won Hyung; Hwang, Won Jae; Yoon, Sug Hwa; Shin, Yong Sup; Son, Soo Chang; Kim, Hye Ja; Choi, Sae Jin; Lim, Kyu; Hwang, Byung Doo

Abstract

BACKGROUND: We studied the time course of gene expression of dynorphin, enkephalin, c-fos, and the changes of allodynia, and the effect of chemical sympathectomy on the gene expression and allodynia in neuropathic rat.
METHODS
In two groups of rat (Sprague-Dawley), the left L5 and L6 spinal nerves were tight ligated. In gene expression group (N=25), behavioral tests for mechanical allodynia and cold allodynia were perfomed for the next two weeks. After the test of allodynia, the expression of dynorphin, enkephalin, c-fos were assessed by Northern blot hybridization. In chemical sympathectomy group (N=16), after chemical sympathectomy (guanethidine 70 mg/kg intraperitoneally, from postoperative 7 days to 9 days), the changes of allodynia and the gene expression of enkephalin, c-fos were tested.
RESULTS
Mechanical allodynia and cold allodynia was developed on the postoperative 3, 5, 7, 14 days. Preprodynorphin mRNA expression was reached peak level at the postoperative 8 hrs, sustained increase by the postoperative 3 days, but preproenkephalin mRNA expression increased slightly after operation. c-Fos mRNA expression was increased immediately at the postoperative 30 min, 1 hr, returned to normal level thereafter, and increased again on the postoperative 3, 5, 7 days that neuropathic pain was developed. Mechanical allodynia and cold allodynia were decreased by chemical sympathectomy. The increased c-fos mRNA expression and pain at postoperative 7 days was reduced by chemical sympathectomy.
CONCLUSION
These results suggest that the transient gene expression of dynorphin and c-fos after tight ligation of L5 and L6 spinal nerves induces the development neuropathic pain, and late c-fos expression is related to neuropathic pain.