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-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.
Kurihara
Takashi
T
Department 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.
Nonaka
Takahiro
T
Tanabe
Tsutomu
T
D019342:Acetic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D012702:Serotonin Antagonists / Q000494:pharmacology; D013995:Time
D000700:Analgesics; D009292:Narcotic Antagonists; D012702:Serotonin Antagonists; D019342:Acetic Acid