title: Activational action of testosterone on androgen receptors protects males preventing temporomandibular joint pain.
abstract: BACKGROUND
  Testosterone protects male rats from Temporomandibular Joint (TMJ) pain. This study investigated whether this protective effect is mediated by an organizational action of testosterone during nervous system development, by central estrogen and androgen receptors and by the 5α-reduced metabolite of testosterone, dihydrotestosterone.
  
  
  METHODS
  A pharmacological approach was used to assess the ability of the androgen receptor antagonist flutamide, the estrogen receptor antagonist ICI 182 780 and the 5-α reductase inhibitor dutasteride to block the protective effect of testosterone, evaluated through the behavioral response induced by a TMJ injection of 0.5% formalin. Flutamide and ICI 182 780 were injected into the medullary subarachnoid space, and dutasteride and testosterone were systemically administered.
  
  
  RESULTS
  The TMJ injection of 0.5% formalin induced a significant nociceptive behavioral response in gonadectomized male and naïve female, but not in sham gonadectomized male rats, confirming that endogenous testosterone prevents TMJ nociception in males. Testosterone administration prevented formalin-induced TMJ nociception in males gonadectomized either in the neonatal (at the day of birth) or adult period and in naïve female rats, suggesting that the protective effect of testosterone on TMJ nociception does not depend on its organizational actions during critical periods of development. The administration of flutamide and dutasteride but not of ICI 182 780 blocked the protective effect of testosterone.
  
  
  CONCLUSIONS
  We conclude that the protective effect of testosterone on TMJ nociception depends on activational actions of dihydrotestosterone on androgen receptors rather than on organizational androgenic actions during central nervous system development or estrogenic actions.
authors.affiliation: Department of Physiology, Piracicaba Dental School, State University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
authors.forename: L E
authors.initials: LE
authors.lastname: Fanton
authors.affiliation: Department of Physiology, Piracicaba Dental School, State University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
authors.forename: C G
authors.initials: CG
authors.lastname: Macedo
authors.affiliation: Department of Physiology, Piracicaba Dental School, State University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
authors.forename: K E
authors.initials: KE
authors.lastname: Torres-Chávez
authors.affiliation: Laboratory of Pain Physiology, Department of Physiology, Federal University of Parana, Curitiba, Parana, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Fischer
authors.affiliation: Department of Functional and Structural Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil. Electronic address: tambeli@unicamp.br.
authors.forename: C H
authors.initials: CH
authors.lastname: Tambeli
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology*; D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D000068538:Dutasteride / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D005557:Formaldehyde; D000077267:Fulvestrant; D008297:Male; D010146:Pain / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism*; D013704:Temporomandibular Joint / Q000187:drug effects* / Q000503:physiopathology; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D065171:Estrogen Receptor Antagonists; D011944:Receptors, Androgen; D005557:Formaldehyde; D000077267:Fulvestrant; D013739:Testosterone; D004958:Estradiol; D005485:Flutamide; D000068538:Dutasteride
keywords: Androgen receptors; Formalin; Nociception; TMJ; Testosterone