Estrogen and progesterone activate spinal kappa-opiate receptor analgesic mechanisms

摘要: Rats and humans manifest elevated response thresholds to aversive stimuli during gestation parturition. This pregnancy-associated antinociception is mediated, in part, by a spinal cord dynorphin/kappa antinociceptive system. Simulating the maternal pregnancy blood concentration profile (in non-pregnant animals) of 17-beta-estradiol (E2) progesterone (P) produces an opioid which closely approximates that actual pregnancy. The current study was initiated order determine whether sex steroid-induced involves kappa-opiate receptor-coupled system (as does gestation). Additionally, steroid modulation intrathecal (i.t.) effectiveness kappa agonist investigated. associated with simulating E2 P (hormone-stimulated pregnancy, HSP) significantly antagonized i.t. administration nor-binaltorphimine, antagonist highly specific for receptor. indicates exposure (of activates receptor analgesic system, as occurs gestation. Furthermore, HSP, responsiveness U50,488H (kappa-selective) enhanced (approximately 40%). effect abolished animals treated concomitantly hormones systemic naltrexone or nor-binaltorphimine. In contrast effects treatment on U50,488H, no alteration sufentanil observed day 19 HSP over all doses tested (0.1-1 nmol). Thus, (and gestation), less robust constituent intrinsic pain-attenuating systems recruited. pF mediate, at least pF, positive post-synaptically. laboratory previously reported also positively modulates dynorphin content processing its precursor, suggesting presynaptic loci action. female rats possess can be modulated, pre-synaptically well post-synaptically, circulating steroids.