title: 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.affiliation: Department of Medicine, Division of Neuroscience, University of California at San Francisco, San Francisco, CA 94143-0440, United States; Department of Oral & Maxillofacial Surgery, University of California at San Francisco, San Francisco, CA 94143-0440, United States.
authors.forename: E K
authors.initials: EK
authors.lastname: Joseph
authors.affiliation: Department of Medicine, Division of Neuroscience, University of California at San Francisco, San Francisco, CA 94143-0440, United States; Department of Oral & Maxillofacial Surgery, University of California at San Francisco, San Francisco, CA 94143-0440, United States.
authors.forename: P G
authors.initials: PG
authors.lastname: Green
authors.affiliation: Department of Medicine, Division of Neuroscience, University of California at San Francisco, San Francisco, CA 94143-0440, United States; Department of Oral & Maxillofacial Surgery, University of California at San Francisco, San Francisco, CA 94143-0440, United States.
authors.forename: L F
authors.initials: LF
authors.lastname: Ferrari
authors.affiliation: Department of Medicine, Division of Neuroscience, University of California at San Francisco, San Francisco, CA 94143-0440, United States; Department of Oral & Maxillofacial Surgery, University of California at San Francisco, San Francisco, CA 94143-0440, United States. Electronic address: Jon.Levine@ucsf.edu.
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D019332:Endothelin-1; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006710:Homocysteine / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain; D008297:Male; D008715:Methionine / Q000494:pharmacology; D009068:Movement; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D063806:Myalgia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D012019:Reflex Sympathetic Dystrophy / Q000188:drug therapy / Q000503:physiopathology; D014110:Touch; D014732:Vibration
chemical_list: D018712:Analgesics, Non-Narcotic; D002317:Cardiovascular Agents; D019332:Endothelin-1; D006710:Homocysteine; D008715:Methionine
keywords: homocysteine; methionine endothelium; muscle pain; vascular pain