Acetic acid conditioning stimulus induces long-lasting antinociception of somatic inflammatory pain
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Updated: Aug 19, 2026

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
Takashi Kurihara1, Takahiro Nonaka, Tsutomu Tanabe
1Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University, CREST, Japan Science and Technology Corporation, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Abstract:
A wide variety of noxious stimuli are known to induce a powerful inhibition of pain sensation evoked at a remote region of the body. Here we show that an intraperitoneal acetic acid (AA) conditioning stimulus produces long-lasting inhibition of formalin-evoked somatic inflammatory pain behavior in mice. This novel long-lasting antinociception was completely blocked by the 5-hydroxytryptamine type 2A/2C (5-HT(2A/2C)) receptor antagonists, ketanserin and ritanserin, but not by the opioid receptor antagonist, naloxone, and alpha-adrenergic receptor antagonists, phentolamine and yohimbine. In contrast, the 5-HT(3/4) receptor antagonist, tropisetron, significantly potentiated this long-lasting antinociception. The conditioning stimulus significantly upregulated the levels of both tryptophan hydroxylase immunoreactivity in the medulla oblongata and the 5-HT(2A/2C) receptor mRNA level in the spinal cord. These results suggested that the visceral noxious stimulus caused a long-lasting augmentation of the serotonergic inhibitory system and downregulated the somatic inflammatory nociceptive transmission.
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