Evidence for the participation of peripheral 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors in formalin-induced secondary mechanical allodynia and hyperalgesia.

Abstract

The role of 5-HT₂A/₂B/₂C receptors in formalin-induced secondary allodynia and hyperalgesia in rats was assessed. Formalin produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-term secondary mechanical allodynia and hyperalgesia. Pre-treatment for five consecutive days with compound 48/80 (1, 3, 10, 10, and 10 μg/paw) prevented formalin-induced secondary allodynia and hyperalgesia. Ipsilateral, but not contralateral, peripheral pre-treatment (nmol/paw) with the 5-HT₂ receptor agonist DOI (3-30), 5-HT (10-100) or fluoxetine (0.3-3) significantly increased 0.5% formalin-induced secondary allodynia and hyperalgesia in both paws. The pronociceptive effect of DOI (10 nmol/paw), 5-HT (100 nmol/paw) and fluoxetine (1 nmol/paw) was blocked by selective 5-HT₂A (ketanserin), 5-HT₂B (RS-127445), and 5-HT₂C (RS-102221) receptor antagonists. Furthermore, ipsilateral pre-treatment (nmol/paw) with ketanserin (1, 10, and 100), RS-127445 (0.01, 0.1 and 1) or RS-102221 (1, 10 and 100) prevented while post-treatment reversed 1% formalin-induced secondary allodynia and hyperalgesia in both paws. In marked contrast, contralateral injection of the greatest tested dose of 5-HT₂A/₂B/₂C receptor antagonists did not modify long-lasting secondary allodynia and hyperalgesia. These results suggest that 5-HT released from mast cells after formalin injection sensitizes primary afferent neurons via 5-HT₂A/₂B/₂C receptors leading to the development and maintenance of secondary allodynia and hyperalgesia.

• Authors: C Cervantes-Durán, J B Pineda-Farias, M Bravo-Hernández, G N Quiñonez-Bastidas, G C Vidal-Cantú, P Barragán-Iglesias, V Granados-Soto
• Journal: Neuroscience (Neuroscience) Vol. 232 Pg. 169-81 (Mar 01 2013) ISSN: 1873-7544 [Electronic] United States
• PMID: 23219842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• 8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione
• Amphetamines
• Analgesics
• Pyrimidines
• Receptor, Serotonin, 5-HT2A
• Receptor, Serotonin, 5-HT2B
• Receptor, Serotonin, 5-HT2C
• Serotonin Antagonists
• Serotonin Receptor Agonists
• Serotonin Uptake Inhibitors
• Spiro Compounds
• Sulfonamides
• Fluoxetine
• 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine
• Formaldehyde
• Serotonin
• p-Methoxy-N-methylphenethylamine
• Ketanserin
• 4-iodo-2,5-dimethoxyphenylisopropylamine

Topics

• Amphetamines (pharmacology)
• Analgesics (pharmacology)
• Animals
• Dose-Response Relationship, Drug
• Female
• Fluoxetine (pharmacology)
• Formaldehyde (toxicity)
• Hyperalgesia (chemically induced, drug therapy, metabolism)
• Ketanserin (pharmacology)
• Pyrimidines (pharmacology)
• Rats, Wistar
• Receptor, Serotonin, 5-HT2A (metabolism)
• Receptor, Serotonin, 5-HT2B (metabolism)
• Receptor, Serotonin, 5-HT2C (metabolism)
• Serotonin (administration & dosage)
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)
• Selective Serotonin Reuptake Inhibitors (pharmacology)
• Spiro Compounds (pharmacology)
• Sulfonamides (pharmacology)
• p-Methoxy-N-methylphenethylamine (pharmacology)