Intradermal 5-HT induces Fos expression in rat dorsal horn neurons not via 5-HT3 but via 5-HT2A receptors

Abstract We investigated the effects of peripherally administered 5-HT on the secondary neurons in the spinal cord of rats using Fos-like immunoreactivity (FLI) as a marker of neuronal activation. The intradermal administration of 5-HT (30, 60 μ g) induced a large number of FLI neurons in the ipsilateral dorsal horn. In animals given 5-HT 2A receptor agonists (DOI: 0.28∼2.8 μ mol/kg, α -methyl 5-HT: 0.28∼2.8 μ mol/kg) intradermally, immunoreactive neurons were evoked in the same manner as those given 5-HT. Other agonists, including 5-HT 3 receptor agonists ( m -CPG: 16∼32 μ mol/kg, 2-methyl 5-HT: 0.0028∼2.8 μ mol/kg), did not induce FLI neurons at any dose examined. Furthermore, 5-HT 2A receptor antagonist (ketanserin: 1 mg/kg, i.p.) suppressed the expression of FLI in the dorsal horn caused by peripheral 5-HT, but 5-HT 3 receptor antagonist (tropisetron: 1 mg/kg, i.p.) did not. These findings suggest that the 5-HT-induced nociceptive response is mediated by 5-HT 2A receptors in the periphery.