Role of the 5-HT(7) receptor in the effects of intrathecal nefopam in neuropathic pain in rats.

Abstract

Nefopam is a non-opioid analgesic drug, used widely in European countries to control postoperative pain. However, its mechanism of action remains unclear. In this study, the effects of intrathecal nefopam on spinal nerve-ligated induced neuropathic pain in rats were examined and the involvement of the 5-HT7 receptor at the spinal level was determined. Next, a 5-HT7 receptor antagonist (SB-269970) or descending serotonergic pathway ablation agent (5,7-DHT) was administered intrathecally before delivery of the nefopam to determine the contribution of spinal 5-HT7 receptors or descending serotonergic pathway to the activity of nefopam. The concentrations of 5-HT were measured. Intrathecal nefopam dose-dependently produced the antiallodynic effect. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect of the nefopam. 5,7-DHT failed to affect the effect of nefopam. The concentrations of 5-HT in the spinal cord and plasma were decreased in neuropathic pain. Intrathecal nefopam increased the levels of 5-HT in the spinal cord and plasma. Intrathecal nefopam is effective in the attenuation of neuropathic pain induced by spinal nerve ligation and nefopam increases the level of 5-HT. Additionally, the 5-HT7 receptor is involved in the antiallodynic action of nefopam in the spinal cord.

• Authors: Lee Jae Dam, Lin Hai, Yoon Myung Ha
• Journal: Neuroscience letters (Neurosci Lett) Vol. 566 Pg. 50-4 (Apr 30 2014) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 24561091 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Analgesics, Non-Narcotic
• Phenols
• Receptors, Serotonin
• SB 269970
• Serotonin Antagonists
• Sulfonamides
• serotonin 7 receptor
• Serotonin
• Nefopam

Topics

• Analgesics, Non-Narcotic (pharmacology, therapeutic use)
• Animals
• Dose-Response Relationship, Drug
• Hyperalgesia (drug therapy, metabolism, physiopathology)
• Injections, Spinal
• Male
• Nefopam (pharmacology, therapeutic use)
• Neuralgia (drug therapy, metabolism, physiopathology)
• Phenols (pharmacology)
• Rats, Sprague-Dawley
• Receptors, Serotonin (metabolism)
• Serotonin (metabolism)
• Serotonin Antagonists (pharmacology)
• Spinal Cord (metabolism)
• Spinal Nerves (injuries)
• Sulfonamides (pharmacology)