Experimental & Clinical Pharmacology
Role of peripheral versus spinal 5-HT7 receptors in the modulation of pain undersensitizing conditions
Article first published online: 11 JAN 2012
© 2011 European Federation of International Association for the Study of Pain Chapters
European Journal of Pain
Volume 16, Issue 1, pages 72–81, January 2012
How to Cite
Brenchat, A., Zamanillo, D., Hamon, M., Romero, L. and Vela, J.M. (2012), Role of peripheral versus spinal 5-HT7 receptors in the modulation of pain undersensitizing conditions. European Journal of Pain, 16: 72–81. doi: 10.1016/j.ejpain.2011.07.004
Conflicts of interestsThe authors state that there were no conflicts of interests in respect to the work reported in this paper.
- Issue published online: 11 JAN 2012
- Article first published online: 11 JAN 2012
- Manuscript Accepted: 4 JUL 2011
Several studies have suggested that 5-HT7 receptors are involved in nociceptive processing but the exact contribution of peripheral versus central 5-HT7 receptors still needs to be elucidated. In the present study, the respective roles of peripheral and spinal 5-HT7 receptors in the modulation of mechanical hypersensitivity were investigated under two different experimental pain conditions. In a first set of experiments, the selective 5-HT7 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-HT7 receptors exerts antinociceptive effects at the level of the spinal cord and pronociceptive effects at the periphery. The antinociceptive effect mediated by central 5-HT7 receptors seems to predominate over the pronociceptive effect at the periphery when a selective 5-HT7 receptor agonist is systemically administered.