title: Rapid estrogenic effects on TMJ-responsive brainstem neurons.
abstract: Estrogen status is a risk factor for temporomandibular muscle and joint disorders (TMJD) and other craniofacial pain conditions. The basis for estrogen modulation of pain is poorly understood and has often been attributed to long-term genomic effects. However, estrogens also act rapidly through membrane-initiated mechanisms to alter neural activity. To assess if estrogens act rapidly to affect TMJ-responsive neurons, we applied 17β-estradiol (E2) directly at the spinomedullary (Vc/C(1-2)) region, the initial brainstem site for synaptic integration of TMJ sensory signals, while recording single neuron activity. In ovariectomized female rats, E2 rapidly (within 10 minutes) and reversibly reduced TMJ-evoked neural activity at the Vc/C(1-2) region. The effect was estrogen receptor (ER) subtype-specific, since ERβ agonists inhibited, while an ERβ agonist enhanced, evoked activity. A membrane-mediated mechanism was indicated, since the membrane-impermeable analogue, E(2)-BSA, mimicked the inhibitory effect of E2 and was prevented by an ER antagonist. This study demonstrated that E2 acted rapidly, through membrane-mediated pathways, and locally at the Vc/C(1-2) region, to modulate sensory signals from the TMJ region. These results were consistent with the hypothesis that estrogens can act rapidly at the level of the trigeminal brainstem complex to influence sensory integration of TMJ-related information.
authors: Dept. of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN 55455, USA.
authors: A
authors: A
authors: Tashiro
authors: K
authors: K
authors: Okamoto
authors: D A
authors: DA
authors: Bereiter
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D000077267:Fulvestrant; D008024:Ligands; D009434:Neural Pathways / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D010052:Ovariectomy; D010636:Phenols; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D059010:Single-Cell Analysis; D013116:Spinal Cord / Q000187:drug effects; D013569:Synapses / Q000187:drug effects; D013704:Temporomandibular Joint / Q000294:innervation*; D013997:Time Factors; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects; D014278:Trigeminal Nuclei / Q000187:drug effects; D011422:Propionates
chemical_list: D000255:Adenosine Triphosphate; D004958:Estradiol; D004965:Estrogen Antagonists; D047629:Estrogen Receptor beta; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D000077267:Fulvestrant; D008024:Ligands; D009570:Nitriles; D010636:Phenols; D011720:Pyrazoles; D012710:Serum Albumin, Bovine; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C043090:estradiol-bovine serum albumin; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol