Different role of spinal 5-HT(hydroxytryptamine)7 receptors and descending serotonergic modulation in inflammatory pain induced in formalin and carrageenan rat models.

Abstract

BACKGROUND:

Spinal serotonin (5-HT) receptors 3 (5-HT3R) and 7 (5-HT7R) are differentially involved in facilitatory or inhibitory descending modulation, respectively. Electrophysiological studies of the spinal cord have demonstrated that 5-HT3R is involved in nociception induced by intraplantar injection of formalin, but not carrageenan. In addition, depletion of spinal serotonin has been shown to attenuate pain behaviour in the formalin test, but there have been no such reports regarding the carrageenan model. This study compared the role of 5-HT7R and the influence of descending serotonergic modulation between formalin- and carrageenan-induced inflammatory pain.

METHODS:

Effects of intrathecal (i.t.) AS-19 (5-HT7R agonist) and SB-269970 (5-HT3R antagonist) on flinching response in the formalin test and mechanical allodynia in the carrageenan model were evaluated in male Sprague-Dawley rats. The effect of serotonin depletion by i.t. 5,7-dihydroxytryptamine was also examined in the two models.

RESULTS:

Intrathecal AS-19 significantly reduced the flinching responses in the formalin test (P<0.01), which was reversed by i.t. SB269970. However, neither AS-19 nor SB269970 produced a significant change in mechanical allodynia in the carrageenan model. Depletion of spinal serotonin attenuated the flinching response in phase 2 of the formalin test (P<0.01), but increased mechanical allodynia in the carrageenan model compared with controls (P<0.01).

CONCLUSIONS:

Spinal 5-HT7R plays a significant inhibitory role in descending serotonergic modulation in pain induced by formalin but not carrageenan. Descending serotonergic modulation is differentially involved in inflammatory pain induced by formalin and carrageenan, with facilitatory and inhibitory effects, respectively.

• Authors: J Yang, H B Bae, H G Ki, J M Oh, W M Kim, H G Lee, M H Yoon, J I Choi
• Journal: British journal of anaesthesia (Br J Anaesth) Vol. 113 Issue 1 Pg. 138-47 (Jul 2014) ISSN: 1471-6771 [Electronic] England
• PMID: 24129596 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author [2013]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Receptors, Serotonin
• Receptors, Serotonin, 5-HT3
• serotonin 7 receptor
• Formaldehyde
• Serotonin
• Carrageenan

Topics

• Animals
• Carrageenan
• Disease Models, Animal
• Formaldehyde
• Hyperalgesia (chemically induced, physiopathology)
• Inflammation (chemically induced, physiopathology)
• Male
• Pain (chemically induced, physiopathology)
• Pain Measurement (methods)
• Pain Threshold (physiology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Serotonin (physiology)
• Receptors, Serotonin, 5-HT3 (physiology)
• Serotonin (deficiency, metabolism, physiology)
• Spinal Cord (metabolism)