Amino acid release at the spinomedullary junction after inflammation of the TMJ region in male and female rats

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Abstract
Temporomandibular joint (TMJ) disorders are painful conditions that are more prevalent in women than men. This study tested the hypothesis that acute inflammation of the TMJ region evoked sex-related changes in amino acid transmitter concentrations at the trigeminal subnucleus/upper cervical cord (Vc/C2) junction, the major terminal zone for TMJ sensory afferents. Microdialysis samples were collected in male, intact and ovariectomized (OvX) female rats after injection of mustard oil into the TMJ region (TMJ-MO) under barbiturate anesthesia. Males displayed increases in glutamate, aspartate and serine at 5 min and secondary increases 40-45 min after TMJ-MO. Intact and OvX females given low dose estrogen (LE2) displayed increases in glutamate, aspartate and serine at 5 min but no secondary increase at 40 min, while OvX females given high dose estrogen (HE2) revealed no increases after TMJ-MO. Glycine increased 20 min after TMJ-MO in males and cycling females, but not in OvX rats. Perfusion of high potassium through the probe evoked similar increases in glutamate, aspartate and glycine in all groups. In separate experiments, perfusion of the glutamate-aspartate reuptake inhibitor, L-trans-2,4-pyrrolidine dicarboxylate (PDC), through the probe caused a prompt elevation in glutamate that was significantly greater in HE2 than LE2 females or males. These results suggested sex hormone status affects glutamatergic neurotransmission at the Vc/C2 junction by acting, in part, through modulation of glutamate reuptake. Altered amino acid transmitter release and/or availability at the Vc/C2 junction may contribute to differential processing of sensory input from the TMJ region in males and females.