Spinal 5-HT5A receptors mediate 5-HT-induced antinociception in several pain models in rats
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 determine...
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Published in | Pharmacology, biochemistry and behavior Vol. 120; pp. 25 - 32 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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Elsevier Inc
01.05.2014
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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, 10–100nmol) or 5-carboxamidotryptamine (5-CT, 0.03–0.3nmol) 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 10nmol). In addition, 5-HT-induced spinal antinociception in the capsaicin and acetic acid tests was blocked by SB-699551 (10nmol). 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.
•Intrathecal 5-HT or 5-CT prevented formalin-induced nociception.•5-HT reduced capsaicin- and acetic acid-induced nociception.•SB-699551 diminished 5-HT- or 5-CT-induced spinal antinociception.•5-HT5A receptors were expressed in the dorsal spinal cord and DRG.•Formalin injection increased the expression of 5-HT5A receptors in the spinal cord. |
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AbstractList | 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. 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, 10–100nmol) or 5-carboxamidotryptamine (5-CT, 0.03–0.3nmol) 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 10nmol). In addition, 5-HT-induced spinal antinociception in the capsaicin and acetic acid tests was blocked by SB-699551 (10nmol). 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. •Intrathecal 5-HT or 5-CT prevented formalin-induced nociception.•5-HT reduced capsaicin- and acetic acid-induced nociception.•SB-699551 diminished 5-HT- or 5-CT-induced spinal antinociception.•5-HT5A receptors were expressed in the dorsal spinal cord and DRG.•Formalin injection increased the expression of 5-HT5A receptors in the spinal cord. |
Author | Muñoz-Islas, Enriqueta Pineda-Farias, Jorge B. Granados-Soto, Vinicio Barragán-Iglesias, Paulino Bravo-Hernández, Mariana Cervantes-Durán, Claudia Quiñonez-Bastidas, Geovanna N. Vidal-Cantú, Guadalupe C. |
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Keywords | Spinal cord 5-HT5A receptors Rat Serotonin Inflammatory pain 5-HT(5A) receptors |
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SubjectTerms | 5-HT5A receptors Acetic Acid Animals Capsaicin Female Inflammatory pain Pain - chemically induced Pain - drug therapy Pain Measurement Rat Rats Rats, Wistar Receptors, Serotonin - biosynthesis Receptors, Serotonin - drug effects Serotonin Serotonin - analogs & derivatives Serotonin - pharmacology Serotonin Antagonists - therapeutic use Serotonin Receptor Agonists - pharmacology Spinal cord Spinal Cord - drug effects Spinal Cord - metabolism |
Title | Spinal 5-HT5A receptors mediate 5-HT-induced antinociception in several pain models in rats |
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