Role of peripheral versus spinal 5-HT(7) receptors in the modulation of pain undersensitizing conditions
| Autor: | A, Brenchat, D, Zamanillo, M, Hamon, L, Romero, J M, Vela |
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| Rok vydání: | 2011 |
| Předmět: |
Male
2-Hydroxyphenethylamine Analysis of Variance Dose-Response Relationship Drug Foot Administration Oral Pain Denervation Injections Rats Serotonin Receptor Agonists Spinal Cord Physical Stimulation Receptors Serotonin Animals Neuralgia Pyrazoles Peripheral Nerves Capsaicin Rats Wistar Sciatic Neuropathy Injections Spinal Pain Measurement |
| Zdroj: | European journal of pain (London, England). 16(1) |
| ISSN: | 1532-2149 |
| Popis: | Several studies have suggested that 5-HT(7) receptors are involved in nociceptive processing but the exact contribution of peripheral versus central 5-HT(7) receptors still needs to be elucidated. In the present study, the respective roles of peripheral and spinal 5-HT(7) receptors in the modulation of mechanical hypersensitivity were investigated under two different experimental pain conditions. In a first set of experiments, the selective 5-HT(7) receptor agonist, E-57431, was systemically, intrathecally or peripherally (intraplantarly) administered to rats sensitized by intraplantar injection of capsaicin. Oral administration of E-57431 (1.25-10 mg/kg) was found to exert a clear-cut dose-dependent reduction of capsaicin-induced mechanical hypersensitivity. Interestingly, intrathecal administration of E-57431 (100 μg) also inhibited mechanical hypersensitivity secondary to capsaicin injection. In contrast, a dose-dependent enhancement of capsaicin-induced mechanical hypersensitivity was observed after local intraplantar injection of E-57431 (0.01-1 μg). In a second set of experiments, E-57431 was systemically or intrathecally administered to rats submitted to neuropathic pain (spared nerve injury model). Significant inhibition of nerve injury-induced mechanical hypersensitivity was found after intraperitoneal (10 mg/kg) as well as intrathecal (100 μg) administration of E-57431 in this chronic pain model. These studies provide evidence that, under sensitizing neurogenic/neuropathic conditions, activation of 5-HT(7) receptors exerts antinociceptive effects at the level of the spinal cord and pronociceptive effects at the periphery. The antinociceptive effect mediated by central 5-HT(7) receptors seems to predominate over the pronociceptive effect at the periphery when a selective 5-HT(7) receptor agonist is systemically administered. |
| Databáze: | OpenAIRE |
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