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The antinociceptive role of spinal 5-HT_5A receptors in rat models of pain along with their expression was evaluated in the spinal cord and dorsal root ganglion (DRG). Nociception was assessed in the formalin, capsaicin, and acetic acid writhing tests. The expression of 5-HT_5A receptors was determined by Western blot analysis. Intrathecal treatment with serotonin (5-HT, 10–100 nmol) or 5-carboxamidotryptamine (5-CT, 0.03–0.3 nmol) dose-dependently prevented 1% formalin-induced nociception. Furthermore, 5-HT reduced capsaicin- and acetic acid-induced nociception. 5-HT- or 5-CT-induced antinociception in the formalin test was diminished by the selective 5-HT_5A receptor antagonist N-[2-(dimethylamino)ethyl]-N-[[4′-[[(2-phenylethyl)amino] methyl][1,1′-biphenyl]-4-yl]methyl]cyclopentanepropanamide dihydrochloride (SB-699551; 3 and 10 nmol). In addition, 5-HT-induced spinal antinociception in the …