Acetic acid conditioning stimulus induces long-lasting antinociception of somatic inflammatory pain

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-HT2A/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-HT3/4 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-HT2A/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. (C) 2003 Elsevier Science Inc. All rights reserved.