Pronociceptive role of peripheral and spinal 5-HT7 receptors in the formalin test

Héctor I. Rocha-González, Alfredo Meneses, Susan M. Carlton, Vinicio Granados-Soto

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    Abstract

    The possible pronociceptive role of peripheral and spinal 5-HT7 receptors in the formalin test was assessed. Local administration of 5-HT 7 (SB-269970, 2.5-77.1 nmol/paw), but not 5-HT1A (WAY-100635, 1-60 nmol/paw), receptor antagonist significantly reduced formalin-induced flinching. Local 5-hydroxytryptamine (5-HT, 3-100 nmol/paw) or 5-carboxamidotryptamine (5-CT, 0.3-3 nmol/paw) (a 5-HT7/1A receptor agonist) augmented, in a dose-dependent manner, 0.5% formalin-induced nociceptive behavior. The local pronociceptive effect of 5-HT or 5-CT was significantly reduced by SB-269970 (25 and 77.1 nmol/paw), but not by WAY-100635 (10 nmol/paw). 5-HT7 receptors were observed in myelinated and unmyelinated axons of the digital nerves in rat hindpaw. Intrathecal SB-269970 (2.5-77.1 nmol/rat) or WAY-100635 (1-50 nmol/rat) did not modify 1% formalin-induced nociceptive behavior. Spinal 5-HT (25-200 nmol/rat) significantly reduced formalin-induced flinching behavior during phase 2. At lower doses (0.1-3 nmol/rat) intrathecal 5-CT dose-dependently increased flinching during phase 2. In contrast, higher doses (10-30 nmol/rat) of 5-CT reduced formalin-induced nociceptive behavior during both phases. The spinal pronociceptive effect of 5-CT was reduced by SB-269970 (7.7-77 nmol/rat), but not by WAY-100635 (10 nmol/rat). In addition, the spinal antinociceptive effect of 5-CT was partially reversed by WAY-100635 (10 nmol/rat). The spinal antinociceptive effect of 5-HT was unaffected either by SB-269970 (77 nmol/rat) or WAY-100635 (10 nmol/rat). Data suggest that 5-HT7, but not 5-HT1A, receptors play a pronociceptive role in peripheral and spinal sites in the rat formalin test.

    Original languageEnglish (US)
    Pages (from-to)182-192
    Number of pages11
    JournalPain
    Volume117
    Issue number1-2
    DOIs
    StatePublished - Sep 1 2005

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    Keywords

    • 5-HT receptor
    • 5-HT receptor
    • Hyperalgesia
    • SB-269970
    • Serotonin
    • Spinal processing

    ASJC Scopus subject areas

    • Neurology
    • Clinical Neurology
    • Anesthesiology and Pain Medicine

    Cite this

    Rocha-González, H. I., Meneses, A., Carlton, S. M., & Granados-Soto, V. (2005). Pronociceptive role of peripheral and spinal 5-HT7 receptors in the formalin test. Pain, 117(1-2), 182-192. https://doi.org/10.1016/j.pain.2005.06.011