Role of peripheral versus spinal 5-HT(7) receptors in the modulation of pain undersensitizing conditions.
Eur J Pain
; 16(1): 72-81, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-21843960
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Dolor
/
Nervios Periféricos
/
Pirazoles
/
Médula Espinal
/
2-Hidroxifenetilamina
/
Receptores de Serotonina
/
Agonistas de Receptores de Serotonina
Límite:
Animals
Idioma:
En
Revista:
Eur J Pain
Asunto de la revista:
NEUROLOGIA
/
PSICOFISIOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
España