Spinal 5-HT5A receptors mediate 5-HT-induced antinociception in several pain models in rats

Abstract 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 capsaicin and acetic acid tests was blocked by SB-699551 (10 nmol). Given alone, intrathecal injection of SB-699551 did not affect nociception induced by any irritant. 5-HT 5A receptors were expressed in the dorsal spinal cord and DRG, even though formalin injection increased after 24 h 5-HT 5A receptor expression only in the spinal cord. Data suggest that 5-HT and 5-CT produce antinociception by activation of spinal 5-HT 5A receptors in both the spinal cord and DRG. Furthermore, our results suggest that spinal 5-HT 5A receptors play an antinociceptive role in several pain models in rats. 5-HT 5A receptors may provide a therapeutic target to develop analgesic drugs.