Behavioral signs of acute pain produced by application of endothelin-1 to rat sciatic nerve

Neuroreport. 1998 Jul 13;9(10):2279-83. doi: 10.1097/00001756-199807130-00025.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Administration, Topical
  • Adrenergic alpha-Agonists / pharmacology
  • Analgesics, Opioid / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Drug Interactions
  • Endothelin-1 / administration & dosage
  • Endothelin-1 / pharmacology*
  • Epinephrine / pharmacology
  • Male
  • Microcirculation
  • Morphine / pharmacology
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Pain / chemically induced*
  • Pain / psychology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Endothelin A
  • Receptors, Endothelin / drug effects
  • Sciatic Nerve / drug effects*


  • Adrenergic alpha-Agonists
  • Analgesics, Opioid
  • Endothelin-1
  • Narcotic Antagonists
  • Receptor, Endothelin A
  • Receptors, Endothelin
  • Naloxone
  • Morphine
  • Epinephrine