Reference

Contribution of the peripheral 5-HT2A receptor to mechanical hyperalgesia in a rat model of neuropathic pain

Contribution of the peripheral 5-HT2A receptor to mechanical hyperalgesia in a rat model of neuropathic pain. Nitanda, Aya; Yasunami, Naho; Tokumo, Kohji; Fujii, Hiromitsu; Hirai, Takao; Nishio, Hiroaki (Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan). Neurochemistry International, 47(6), 394-400 (English) 2005 Elsevier B.V. CODEN: NEUIDS. ISSN: 0197-0186. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2, 14 We investigated the effect of 5-HT receptor antagonists on mech. hyperalgesia obsd. in a neuropathic pain rat model prepd. by chronic constriction injury of the sciatic nerve. NAN-190, a 5-HT1A receptor antagonist, (-)-pindolol, a 5-HT1A/1B receptor antagonist, and tropisetron, a 5-HT3/4 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-HT2A receptor antagonists, significantly elevated the pain threshold in the hyperalgesic hind limb, but not in the normal hind limb. In spite of its high affinity for the 5-HT2A receptor, methysergide only slightly elevated the pain threshold in the hyperalgesic hind limb. Pre-treatment with methysergide significantly antagonized the inhibitory effect of sarpogrelate on hyperalgesia. Furthermore, the 5-HT2A receptor specific binding activity of 3H-ketanserin detd. for the hyperalgesic hind limb did not differ from that of the normal hind limb. From these results, we propose that the 5-HT2A receptor in the hyperalgesic hind paw function as an agonist-independent active receptor following constriction of the sciatic nerve, and that sarpogrelate and ketanserin act as inverse agonists of this receptor and suppress its activation. Methysergide may act as a neutral antagonist that blocks the effect of inverse agonists on the 5-HT2A receptor. There are some commonly used reagents like 26328-11-0 in this article. .