title: Intratesticular Bradykinin Involvement in Rat Testicular Pain Models.
abstract: OBJECTIVE
  To clarify the role of bradykinin in urogenital pain, we investigated bradykinin involvement in rat models of testicular pain.
  
  
  METHODS
  Bradykinin (0.1, 0.3, 1, 3 and 10 mmol/L) or distilled water was injected into the testes of male Wistar rats, and induced pain behaviors in conscious rats were evaluated. The effect of pretreatment with bradykinin B2 receptor antagonist FK3657 on bradykinin-induced pain behavior was then examined. We also evaluated the analgesic effect of FK3657 in a rat acetic acid-induced testicular pain as well as changes in the intratesticular bradykinin concentration after testicular injection of acetic acid.
  
  
  RESULTS
  An injection of bradykinin into the testes of conscious rats induced pain behaviors that were dose-proportionally reduced by prior administration of FK3657. In addition, FK3657 dose-dependently inhibited the pain responses induced by testicular injection of 1% acetic acid. An increase in intratesticular bradykinin concentration was detected after the testicular injection of 1% acetic acid.
  
  
  CONCLUSIONS
  Here, we found that intratesticular bradykinin evokes pain behavior via stimulation of bradykinin B2 receptors and that intratesticular acetic acid injection induces intratesticular bradykinin synthesis, consequently leading to pain behavior. These findings suggest that the potential utility of bradykinin B2 receptor antagonists as a novel target for treating urogenital pain.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Yoshino
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Katsuro
authors.initials: K
authors.lastname: Yoshioka
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Yuyama
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeda
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology*; D065094:Bradykinin B2 Receptor Antagonists / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007267:Injections; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D011804:Quinolines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D013737:Testis / Q000378:metabolism
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; C105311:FR 173657; D011804:Quinolines; D043782:Receptor, Bradykinin B2; D019342:Acetic Acid; D001920:Bradykinin
keywords: C fibers; bradykinin; testicular pain