Behavioral signs of acute pain produced by application of endothelin-1 to rat sciatic nerve.
We examined whether endothelin-1 (ET-1), a potent vasoconstrictive peptide secreted in high concentration by metastatic prostate cancer cells, produces endothelin receptor-dependent pain behavior when applied to rat sciatic nerve. ET-1 (200-800 microM) applied to the epineurial surface of rat sciatic nerve produced reliable, robust, unilateral hindpaw flinching lasting 60 min. Pre-emptive systemic morphine completely blocked this effect in a naloxone-reversible manner, suggesting that this behavior was pain-related. Equipotent doses of epineurially applied epinephrine had no effect, suggesting that ET-1 effects are on tissue sites other than sciatic nerve microvessels. Prior and co-administration of BQ-123, an endothelin-A (ET(A)) receptor antagonist, also blocked ET-1-induced hindpaw flinching establishing that pain behavior induced by ET-1 application to rat sciatic nerve is ET(A) receptor mediated.
Molecular Neurobiology of Pain, Pain Research Center, Department of Anesthesia, Brigham and Women's Hospital, Boston, MA 02115, USA.
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Davar
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Hans
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Fareed
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Sinnott
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Strichartz
D000208:Acute Disease; D000287:Administration, Topical; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004347:Drug Interactions; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D008297:Male; D008833:Microcirculation; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced* / Q000523:psychology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D019332:Endothelin-1; D009292:Narcotic Antagonists; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D009270:Naloxone; D009020:Morphine; D004837:Epinephrine