Role of spinal 5-HT2 receptors subtypes in formalin-induced long-lasting hypersensitivity.

Abstract

BACKGROUND:

The purpose of this study was to determine the role of spinal 5-HT2A, 5-HT2B and 5-HT2C receptors in the development and maintenance of formalin-induced long-lasting secondary allodynia and hyperalgesia in rats, as well as their expression in the dorsal root ganglia (DRG) during this process.

METHODS:

0.5-1% formalin was used to produce long-lasting secondary allodynia and hyperalgesia in rats. Western blot was used to determine 5-HT2 receptors expression in DRG.

RESULTS:

Formalin (0.5-1%) injection produced long-lasting (1-12 days) secondary allodynia and hyperalgesia in both ipsilateral and contralateral hind paws. Intrathecal pre-treatment or post-treatment with the 5-HT2 receptor agonist, DOI (1-10nmol), increased 0.5% formalin-induced secondary allodynia and hyperalgesia in both paws. In contrast, intrathecal pre-treatment with the selective 5-HT2A (ketanserin 1-100nmol), 5-HT2B (RS 127445 1-100nmol) or 5-HT2C (RS 102221 1-100nmol) receptor antagonists prevented and reversed, respectively, 1% formalin-induced secondary allodynia and hyperalgesia in both paws. Likewise, the pronociceptive effect of DOI (10nmol) was blocked by ketanserin, RS 127445 or RS 102221 (0.01nmol). 5-HT2A/2B/2C receptors were expressed in DRG of naïve rats. Formalin injection (1%) increased bilaterally 5-HT2A/2B receptors expression in DRG. In contrast, formalin injection decreased 5-HT2C receptors expression bilaterally in DRG.

CONCLUSION:

Data suggest that spinal 5-HT2A/2B/2C receptors have pronociceptive effects and participate in the development and maintenance of formalin-induced long-lasting hypersensitivity. These receptors are expressed in DRG and their expression is modulated by formalin.

• Authors: Claudia Cervantes-Durán, Guadalupe C Vidal-Cantú, Beatriz Godínez-Chaparro, Vinicio Granados-Soto
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 68 Issue 2 Pg. 434-42 (Apr 2016) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 26922550 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Chemical References

• 8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione
• Pyrimidines
• Receptors, Serotonin, 5-HT2
• Spiro Compounds
• Sulfonamides
• 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine
• Formaldehyde
• Ketanserin

Topics

• Animals
• Female
• Formaldehyde (pharmacology)
• Ganglia, Spinal (drug effects, metabolism)
• Hyperalgesia (chemically induced, metabolism)
• Ketanserin (pharmacology)
• Pain Measurement (methods)
• Pyrimidines (pharmacology)
• Rats
• Rats, Wistar
• Receptors, Serotonin, 5-HT2 (metabolism)
• Spinal Cord (drug effects, metabolism)
• Spiro Compounds (pharmacology)
• Sulfonamides (pharmacology)