title: Endothelin-1 induces itch and pain in the mouse cheek model.
abstract: OBJECTIVE
  To date, suggestions that endothelin-1 (ET-1) causes nociception and pruritus are based on results in preclinical models in which responses to pruritic and nociceptive stimuli cannot be distinguished. This study reexamines these sensory effects of ET-1 in the new mouse cheek model, in which pruritogens and algogens evoke distinct behavioral responses.
  
  
  METHODS
  Mice received intradermal (i.d.) injections of test substances into the left cheek and bouts of hind limb scratches or forepaw wipes, directed to the injection site, were considered indicative of pruritus and nociception, respectively.
  
  
  RESULTS
  Histamine and capsaicin selectively evoked scratching and wipes, respectively, whereas ET-1 (3-60 pmol) promoted dose-dependent bouts of both behaviors. While scratching and wipe responses to ET-1 (30 pmol) were potentiated by BQ-788 (an ET(B) receptor antagonist) and reduced by co-injection of BQ-788 plus BQ-123 (an ET(A) receptor antagonist), BQ-123 alone inhibited scratching responses only. CTOP (μ-opioid receptor selective antagonist) only augmented scratching responses to ET-1, whereas DAMGO (μ-opioid receptor selective agonist) reduced both behaviors. Loratadine (histamine H(1) receptor antagonist) marginally reduced scratching, but markedly suppressed wipes.
  
  
  CONCLUSIONS
  These results demonstrate that ET-1 evokes pruritic and nociceptive behaviors in the mouse cheek model. Both responses to ET-1 appear to be mediated via ET(A) receptors and subjected to limitation by simultaneous ET(B) receptor activation. Local endogenous opioids acting on μ-opioid receptors selectively modulate the pruritic response to ET-1, whereas histamine, possibly derived from mast cells and acting on H(1) receptors, contributes importantly to the nociceptive effect of ET-1 in this model.
authors.affiliation: Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Lenyta Oliveira
authors.initials: LO
authors.lastname: Gomes
authors.forename: Daniela Balz
authors.initials: DB
authors.lastname: Hara
authors.forename: Giles Alexander
authors.initials: GA
authors.lastname: Rae
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002211:Capsaicin / Q000008:administration & dosage; D002610:Cheek; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000008:administration & dosage / Q000378:metabolism*; D006632:Histamine / Q000008:administration & dosage; D007271:Injections, Intradermal; D008297:Male; D051379:Mice; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D011537:Pruritus / Q000209:etiology / Q000503:physiopathology*; D044022:Receptor, Endothelin A / Q000819:agonists / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000819:agonists / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D011969:Receptors, Histamine H1; D017450:Receptors, Opioid, mu; D006632:Histamine; D002211:Capsaicin