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Spinal 5-HT₅A Receptors Mediate 5-HT-induced Antinociception in Several Pain Models in Rats

Spinal 5-HT₅A Receptors Mediate 5-HT-induced Antinociception in Several Pain Models in Rats

Enriqueta Muñoz-Islas, Guadalupe C Vidal-Cantú, Mariana Bravo-Hernández, Claudia Cervantes-Durán, Geovanna N Quiñonez-Bastidas, Jorge B Pineda-Farias, Paulino Barragán-Iglesias, Vinicio Granados-Soto

Pharmacol Biochem Behav. 2014 May;120:25-32.

PMID: 24517902

Abstract:

The antinociceptive role of spinal 5-HT5A 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-HT5A 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-HT5A 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-HT5A receptors were expressed in the dorsal spinal cord and DRG, even though formalin injection increased after 24h 5-HT5A receptor expression only in the spinal cord. Data suggest that 5-HT and 5-CT produce antinociception by activation of spinal 5-HT5A receptors in both the spinal cord and DRG. Furthermore, our results suggest that spinal 5-HT5A receptors play an antinociceptive role in several pain models in rats. 5-HT5A receptors may provide a therapeutic target to develop analgesic drugs.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP864741957	SB 699551 dihydrochloride		864741-95-7	Price

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