title: Coactivation of μ- and κ-Opioid Receptors May Mediate the Protective Effect of Testosterone on the Development of Temporomandibular Joint Nociception in Male Rats.
abstract: OBJECTIVE
  To investigate whether the protective effect of testosterone on the development of temporomandibular joint (TMJ) nociception in male rats is mediated by the activation of central opioid mechanisms.
  
  
  METHODS
  Experiments were performed on 156 male Wistar rats. A pharmacologic approach was used to assess the ability of opioid receptor antagonists infused into the dorsal portion of the brainstem and adjacent to the caudal component (subnucleus caudalis) of the spinal trigeminal nucleus to block the protective effect of testosterone in male rats. The TMJ injection of 0.5% formalin was used as a nociceptive stimulus. One-way or two-way ANOVA was used for data analyses.
  
  
  RESULTS
  The injection of 0.5% formalin into the TMJ induced a significant nociceptive behavior in gonadectomized male rats (P < .05), but not in naïve, sham, and testosterone-replaced gonadectomized rats, confirming that testosterone prevents the development of TMJ nociception. The injection of either the nonselective opioid receptor antagonist naloxone (15 μg) or the simultaneous injection of the μ-opioid receptor antagonist Cys2, Tyr3, Orn5, Pen7amide (CTOP, 30 μg) and the κ-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI, 90 μg) significantly increased the 0.5% formalin-induced behavioral response in sham and testosterone-replaced gonadectomized rats (P < .05) but had no effect in gonadectomized rats. However, the injection of each selective opioid receptor antagonist alone or the simultaneous injection of μ- or κ- and δ-opioid receptor antagonists had no effect.
  
  
  CONCLUSIONS
  These findings indicate that the protective effect of endogenous testosterone on the development of TMJ nociception in male rats is mediated by the activation of central opioid mechanisms. Furthermore, the coactivation of central μ- and κ-opioid receptors is necessary for testosterone to protect male rats from developing TMJ nociception.
authors.forename: Cristina G
authors.initials: CG
authors.lastname: Macedo
authors.forename: Leticia E
authors.initials: LE
authors.lastname: Fanton
authors.forename: Luana
authors.initials: L
authors.lastname: Fischer
authors.forename: Claudia Herrera
authors.initials: CH
authors.lastname: Tambeli
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects; D005157:Facial Pain / Q000517:prevention & control; D005557:Formaldehyde / Q000009:adverse effects; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D059226:Nociceptive Pain / Q000139:chemically induced; D009919:Orchiectomy; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013704:Temporomandibular Joint / Q000502:physiology*; D013705:Temporomandibular Joint Disorders / Q000517:prevention & control; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology*; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects
chemical_list: D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D005557:Formaldehyde; D009270:Naloxone; C051844:norbinaltorphimine; D013739:Testosterone; D013004:Somatostatin; D009271:Naltrexone