Fanton L E, Macedo C G, Torres-Chávez K E, Fischer L, Tambeli C H
Department of Physiology, Piracicaba Dental School, State University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
Laboratory of Pain Physiology, Department of Physiology, Federal University of Parana, Curitiba, Parana, Brazil.
Pharmacol Biochem Behav. 2017 Jan;152:30-35. doi: 10.1016/j.pbb.2016.07.005. Epub 2016 Jul 25.
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.
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.
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.
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.
睾酮可保护雄性大鼠免受颞下颌关节（TMJ）疼痛的影响。本研究调查了这种保护作用是否由睾酮在神经系统发育过程中的组织作用、中枢雌激素和雄激素受体以及睾酮的5α还原代谢产物二氢睾酮介导。
采用药理学方法评估雄激素受体拮抗剂氟他胺、雌激素受体拮抗剂ICI 182 780和5-α还原酶抑制剂度他雄胺阻断睾酮保护作用的能力，通过TMJ注射0.5%福尔马林诱导的行为反应进行评估。氟他胺和ICI 182 780注入延髓蛛网膜下腔，度他雄胺和睾酮进行全身给药。
TMJ注射0.5%福尔马林在去势雄性和未处理雌性大鼠中诱导出显著的伤害性行为反应，但在假去势雄性大鼠中未诱导出该反应，证实内源性睾酮可预防雄性大鼠的TMJ伤害感受。睾酮给药可预防在新生期（出生当天）或成年期去势的雄性大鼠以及未处理雌性大鼠中福尔马林诱导的TMJ伤害感受，表明睾酮对TMJ伤害感受的保护作用不依赖于其在发育关键期的组织作用。氟他胺和度他雄胺给药可阻断睾酮的保护作用，但ICI 182 780给药未阻断。
我们得出结论，睾酮对TMJ伤害感受的保护作用取决于二氢睾酮对雄激素受体的激活作用，而非中枢神经系统发育过程中的组织雄激素作用或雌激素作用。
