Chronic inflammation and estradiol interact through MAPK activation to affect TMJ nociceptive processing by trigeminal caudalis neurons.
The mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway plays a key role in mediating estrogen actions in the brain and neuronal sensitization during inflammation. Estrogen status is a risk factor in chronic temporomandibular muscle/joint (TMJ) disorders; however, the basis for this relationship is not known. The present study tested the hypothesis that estrogen status acts through the MAPK/ERK signaling pathway to alter TMJ nociceptive processing. Single TMJ-responsive neurons were recorded in laminae I-II at the spinomedullary (Vc/C(1-2)) junction in naïve ovariectomized (OvX) female rats treated for 2 days with high-dose (20 microg/day; HE2) or low-dose estradiol (2 microg/day; LE2) and after chronic inflammation of the TMJ region by complete Freund's adjuvant for 12-14 days. Intra-TMJ injection of ATP (1 mM) was used to activate Vc/C(1-2) neurons. The MAPK/ERK inhibitor (PD98059, 0.01-1 mM) was applied topically to the dorsal Vc/C(1-2) surface at the site of recording 10 min prior to each ATP stimulus. In naïve HE2 rats, low-dose PD98059 caused a maximal inhibition of ATP-evoked activity, whereas even high doses had only minor effects on units in LE2 rats. By contrast, after chronic TMJ inflammation, PD98059 produced a marked and similar dose-related inhibition of ATP-evoked activity in HE2 and LE2 rats. These results suggested that E2 status and chronic inflammation acted, at least in part, through a common MAPK/ERK-dependent signaling pathway to enhance TMJ nociceptive processing by laminae I-II neurons at the spinomedullary junction region.
Tashiro
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Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, 18214 Moos Tower, Minneapolis, 515 Delaware Street SE, Minneapolis, MN 55455, USA. tashi004@umn.edu
Okamoto
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K
Bereiter
D A
DA
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D010052:Ovariectomy; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D012867:Skin / Q000187:drug effects / Q000294:innervation; D013704:Temporomandibular Joint / Q000294:innervation / Q000503:physiopathology*; D014275:Trigeminal Caudal Nucleus / Q000502:physiology*
D004967:Estrogens; C074283:estradiol 3-benzoate; D004958:Estradiol; D000255:Adenosine Triphosphate; D020928:Mitogen-Activated Protein Kinases