| Co-Investigator(Kenkyū-buntansha) |
HIRAI Takao Fukuyama University, Faculty of Pharmacy and Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (80389072)
TAMURA Yutaka Fukuyama University, Faculty of Pharmacy and Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (30217202)
二反田 綾 福山大学, 薬学部, 助手 (80352003)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
We investigated the effect of 5-HT receptor antagonists on mechanical hyperalgesia observed in a neuropathic pain rat model prepared by chronic constriction injury of the sciatic nerve. NAN-190, a 5-HT_<1A> receptor antagonist, (-)-pindolol, a 5-HT_<1A/1B> receptor antagonist, and tropisetron, a 5-HT_<3/4> receptor antagonist, did not affect the pain threshold in the hyperalgesic hind limb to the same extent as in the normal hind limb. However, sarpogrelate and ketanserin, 5-HT_<2A> receptor antagonists, significantly elevated the pain threshold in the hyperalgesic hind limb, but not in the normal hind limb. In order to analyze the possible changes in cellular gene expression, gene analysis of the dorsal-root ganglion cell of rat was performed. In the ganglion cell, presence of DNA and mRNA for 5-HT_<2A> receptor was demonstrated by PCR and RT-PCR assay, respectively. However, mRNA of the hyperalgesic side did not changed from that of the normal side. Furthermore, local application of nerve growth factor (NGF) to the hind limb induced hyperalgesia, which was selectively inhibited by 5-HT_<2A> receptor antagonists. The local application of 4-methylcathechol (4-MC), an inducer of NGF in local tissue, apparently reduced the pain threshold in the hyperalgesia and non-hyperalgesia hind limbs. These results imply that NGF release might be involved in the pathogenesis of hyperalgesia in the neuropathic pain model, though the NGF release mechanism for the partial ligation of sciatic nerve was distinct from that for 4-MC.
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