Alleviative effects of 5-HT_<2A> receptor antagonists on the neuropathic pain

• Project/Area Number: 15500271
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Fukuyama University
• Principal Investigator: NISHIO Hiroaki Fukuyama University, Faculty of Pharmacy and Pharmaceutical Sciences, Professor, 薬学部, 教授 (30034036)
• 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)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥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)
• Keywords: 5-HT_<2A> receptor / Hyperalgesia / Neuropathic pain / Bennett model / Neurogrowth factor / Sarpogrelate / Ketanserin / 4-Methylcatechol / 皮膚表皮角化細胞 / 5-HT受容体サブタイプ / BDNF / GDNF / 一酸化窒素

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.

Research Products

• [Journal Article] Contribution of the peripheral 5-HT2A receptor to mechanical hyperalgesia in a rat model of neurophathic pain. (2005)
  • Author(s): Nitanda.A, Yasunami, N., Tokumo, K., Fujii, H., Hirai, T., Nishio,H.
  • Journal Title: Neurochemistry International 47・6 Pages: 394-400
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Contribution of the peripheral 5-HT_<2A> receptor to mechanical hyperalgesia in a rat model of neuropathic pain. (2005)
  • Author(s): Nitanda, A., Yasunami, N., Tokumo, K., Fujii, H., Hirai, T., Nishio, H.
  • Journal Title: Neurochemistry International 47(6) Pages: 394-400
  • NAID: 110007408825
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Contribution of the peripheral 5-HT2A receptor to mechanical hyperalgesia in a rat model of neuropathic pain. (2005)
  • Author(s): Nitanda, A., Yasunami, N., Tokumo, K., Fujii, H., Hirai, T., Nishio, H.
  • Journal Title: Neurochemistry International 47・6 Pages: 394-400