Flake Natasha M, Bonebreak David B, Gold Michael S
Department of Biomedical Sciences, Dental School, University of Maryland, 666 W. Baltimore St., Rm. 5-A-12, Baltimore, MD 21201, USA.
J Neurophysiol. 2005 Mar;93(3):1585-97. doi: 10.1152/jn.00269.2004. Epub 2004 Nov 3.
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 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's Adjuvant to induce inflammation. Excitability was assessed with depolarizing current injection 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.
包括颞下颌关节紊乱症（TMD）在内的几种疼痛性疾病，在女性中比在男性中更为普遍和严重。尽管这种性别差异的生理基础尚待确定，但雌激素很可能是一个潜在因素。本研究旨在检验以下假设：雌激素会增加大鼠颞下颌关节（TMJ）传入神经的兴奋性，并加剧炎症诱导的这些感觉神经元的敏化。使用全细胞膜片钳技术，对注射生理盐水或完全弗氏佐剂以诱导炎症三天后的去卵巢大鼠以及接受慢性雌激素替代的去卵巢大鼠的逆行标记TMJ神经元进行研究。通过去极化电流注入来评估兴奋性，以确定动作电位阈值、基强度以及对阈上刺激的反应。还评估了自发活动。炎症和雌激素均增加了TMJ神经元的兴奋性，表现为动作电位阈值和基强度降低以及自发活动发生率增加。这些效应是相加的，接受雌激素和炎症刺激的大鼠的神经元兴奋性最高。兴奋性的增加与被动特性和动作电位波形的变化有关，这表明雌激素和炎症会影响TMJ神经元中离子通道的表达和/或特性。重要的是，雌激素对TMJ神经元兴奋性的基线和炎症诱导变化的影响，可能有助于解释在TMD中观察到的显著性别差异，并为这种疼痛状况的治疗提出一个新的靶点。
