Homocysteine-induced attenuation of vascular endothelium-dependent hyperalgesia in the rat.

Abstract

We have recently demonstrated a role of the vascular endothelium in peripheral pain mechanism by disrupting endothelial cell function using intravascular administration of octoxynol-9, a non-selective membrane active agent. As an independent test of the role of endothelial cells in pain mechanisms, we evaluated the effect of homocysteine, an agent that damages endothelial cell function. Mechanical stimulus-induced enhancement of endothelin-1 hyperalgesia in the gastrocnemius muscle of the rat was first prevented then enhanced by intravenous administration of homocysteine, but was only inhibited by its precursor, methionine. Both homocysteine and methionine significantly attenuated mechanical hyperalgesia in two models of ergonomic muscle pain, induced by exposure to vibration, and by eccentric exercise, and cutaneous mechanical hyperalgesia in an ischemia-reperfusion injury model of Complex Regional Pain Syndrome type I, all previously shown responsive to octoxynol-9. This study provides independent support for a role of the endothelial cell in pain syndromes thought to have a vascular basis, and suggests that substances that are endothelial cell toxins can enhance vascular pain.

• Authors: E K Joseph, P G Green, L F Ferrari, J D Levine
• Journal: Neuroscience (Neuroscience) Vol. 284 Pg. 678-684 (Jan 22 2015) ISSN: 1873-7544 [Electronic] United States
• PMID: 25451284 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Analgesics, Non-Narcotic
• Cardiovascular Agents
• Endothelin-1
• Homocysteine
• Methionine

Topics

• Analgesics, Non-Narcotic (pharmacology)
• Animals
• Cardiovascular Agents (pharmacology)
• Disease Models, Animal
• Endothelin-1
• Endothelium, Vascular (drug effects, physiopathology)
• Homocysteine (pharmacology)
• Hyperalgesia (chemically induced, drug therapy, physiopathology)
• Hypoxia-Ischemia, Brain
• Male
• Methionine (pharmacology)
• Movement
• Muscle, Skeletal (drug effects, physiopathology)
• Myalgia (chemically induced, drug therapy, physiopathology)
• Rats, Sprague-Dawley
• Reflex Sympathetic Dystrophy (drug therapy, physiopathology)
• Touch
• Vibration