5-HT(1A) receptors in endogenous regulation of neuropathic hypersensitivity in the rat.

Abstract

The role of medullary and spinal 5-HT(1A) receptors in endogenous regulation of neuropathic hypersensitivity was studied. When administered in the rostroventromedial medulla or subcutaneously, WAY-100635, a 5-HT(1A) receptor antagonist, attenuated mechanical hypersensitivity in rats with a spinal nerve injury. Thermal or mechanical nociception outside of the injured area was not influenced by medial medullary or subcutaneous administration of WAY-100635. Intrathecal administration of WAY-100635 had no significant effect on pain-related behavior. Suppression of mechanical hypersensitivity induced by medial medullary administration of WAY-100635 was reversed by intrathecal administration of WAY-100635 or atipamezole, an alpha2-adrenoceptor antagonist, but not by naloxone, an opioid receptor antagonist. The results indicate that endogenous release of 5-HT, via action on medial medullary 5-HT(1A) receptors, tonically suppresses descending inhibition in neuropathic animals. Following medial medullary administration of a 5-HT(1A) receptor antagonist, descending pain regulatory pathways are disinhibited. This leads to selective attenuation of neuropathic hypersensitivity, due to action on spinal 5-HT(1A) receptors and alpha2-adrenoceptors.

• Authors: Hong Wei, Antti Pertovaara
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 535 Issue 1-3 Pg. 157-65 (Mar 27 2006) ISSN: 0014-2999 [Print] Netherlands
• PMID: 16545367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Antagonists
• Imidazoles
• Narcotic Antagonists
• Piperazines
• Pyridines
• Serotonin 5-HT1 Receptor Antagonists
• Serotonin Antagonists
• atipamezole
• Receptor, Serotonin, 5-HT1A
• Naloxone
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide

Topics

• Adrenergic alpha-Antagonists (administration & dosage, pharmacology)
• Animals
• Dose-Response Relationship, Drug
• Hot Temperature (adverse effects)
• Hyperalgesia (etiology, physiopathology, prevention & control)
• Imidazoles (administration & dosage, pharmacology)
• Injections, Intraventricular
• Injections, Spinal
• Injections, Subcutaneous
• Male
• Naloxone (administration & dosage, pharmacology)
• Narcotic Antagonists (administration & dosage, pharmacology)
• Pain (etiology, physiopathology, prevention & control)
• Pain Measurement (methods)
• Pain Threshold (drug effects)
• Piperazines (administration & dosage, pharmacology)
• Pyridines (administration & dosage, pharmacology)
• Rats
• Rats, Wistar
• Receptor, Serotonin, 5-HT1A (physiology)
• Serotonin 5-HT1 Receptor Antagonists
• Serotonin Antagonists (administration & dosage, pharmacology)
• Spinal Nerves (injuries)