Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Role of peripheral versus spinal 5-HT(7) receptors in the modulation of pain undersensitizing conditions.

Authors: Brenchat, A  Zamanillo, D  Hamon, M  Romero, L  Vela, JM 
Citation: Brenchat A, etal., Eur J Pain. 2012 Jan;16(1):72-81. doi: 10.1016/j.ejpain.2011.07.004.
Pubmed: (View Article at PubMed) PMID:21843960
DOI: Full-text: DOI:10.1016/j.ejpain.2011.07.004

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 mug) 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 mug). 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 mug) 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.

Annotation

Disease Annotations
Gene Ontology Annotations
Objects Annotated

Additional Information

 
RGD Object Information
RGD ID: 6482179
Created: 2012-04-13
Species: All species
Last Modified: 2012-04-13
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.