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1 Biomedical Sciences, Dental School, University of Maryland, Baltimore, Baltimore, MD, USA
* To whom correspondence should be addressed. E-mail: msg001{at}dental.umaryland.edu.
Several painful conditions, including temporomandibular disorders (TMD), are more prevalent and more severe in women than in men. Although the physiological basis for this sex difference remains to be determined, it is likely that estrogen is an underlying factor. The present study was performed in order to test the hypotheses that estrogen increases the excitability of rat temporomandibular joint (TMJ) afferents and exacerbates the inflammation-induced sensitization of these sensory neurons. Retrogradely-labeled TMJ neurons from ovariectomized rats and ovariectomized rats receiving chronic estrogen replacement were studied using whole cell patch clamp techniques three days after injecting the TMJ with either saline or Complete Freund[[rad]]s Adjuvant to induce inflammation. Excitability was assessed with depolarizing current injection in order to determine action potential threshold, rheobase and the response to suprathreshold stimuli. Spontaneous activity was also assessed. Both inflammation and estrogen increased the excitability of TMJ neurons as reflected by decreases in action potential threshold and rheobase and increases in the incidence of spontaneous activity. The effects were additive, with neurons from rats receiving both estrogen and inflammation being the most excitable. The increases in excitability were associated with changes in passive properties and action potential waveform, suggesting that estrogen and inflammation affect the expression and/or properties of ion channels in TMJ neurons. Importantly, the influence of estrogen on both baseline and inflammation-induced changes in TMJ neuronal excitability may help explain the profound sex difference observed in TMD, as well as suggest a novel target for the treatment of this pain condition.
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