Harriott A M, Dessem D, Gold M S
University of Maryland, Baltimore Dental School, Department of Biomedical Sciences, Room 5-A-12 HHH, 666 West Baltimore Street, Baltimore, MD 21201, USA.
Neuroscience. 2006 Aug 11;141(1):433-42. doi: 10.1016/j.neuroscience.2006.03.049. Epub 2006 May 9.
Temporomandibular disorder is a major health problem associated with chronic orofacial pain in the masticatory muscles and/or temporomandibular joint. Evidence suggests that changes in primary afferents innervating the muscles of mastication may contribute to temporomandibular disorder. However, there has been little systematic study of the mechanisms controlling the excitability of these muscle afferents, nor their response to inflammation. In the present study, we tested the hypotheses that inflammation increases the excitability of sensory neurons innervating the masseter muscle of the rat and that the ionic mechanisms underlying these changes are unique to these neurons. We examined inflammation-induced changes in the excitability of trigeminal ganglia muscle neurons following intramuscular injections of complete Freund's adjuvant. Three days after complete Freund's adjuvant injection acutely dissociated, retrogradely labeled trigeminal ganglia neurons were studied using whole cell patch clamp techniques. Complete Freund's adjuvant-induced inflammation was associated with an increase in neuronal excitability marked by a significant decrease in rheobase and increase in the slope of the stimulus response function assessed with depolarizing current injection. The increase in excitability was associated with significant decreases in the rate of action potential fall and the duration of the action potential afterhyperpolarization. These changes in excitability and action potential waveform were associated with significant shifts in the voltage-dependence of activation and steady-state availability of voltage-gated K(+) current as well as significant decreases in the density of voltage-gated K(+) current subject to steady-state inactivation. These data suggest that K(+) channel subtypes may provide novel targets for the treatment of pain arising from inflamed muscle. These results also support the hypothesis that the underlying mechanisms of pain arising from specific regions of the body are unique suggesting that it may be possible, if not necessary to treat pain originating from different parts of the body with specific therapeutic interventions.
颞下颌关节紊乱病是一种与咀嚼肌和/或颞下颌关节慢性口面部疼痛相关的主要健康问题。有证据表明，支配咀嚼肌的初级传入神经的变化可能导致颞下颌关节紊乱病。然而，对于控制这些肌肉传入神经兴奋性的机制及其对炎症的反应，几乎没有系统的研究。在本研究中，我们检验了以下假设：炎症会增加支配大鼠咬肌的感觉神经元的兴奋性，且这些变化背后的离子机制是这些神经元所特有的。我们通过肌肉内注射完全弗氏佐剂，研究了炎症诱导的三叉神经节肌肉神经元兴奋性的变化。在注射完全弗氏佐剂三天后，使用全细胞膜片钳技术对急性分离、逆行标记的三叉神经节神经元进行了研究。完全弗氏佐剂诱导的炎症与神经元兴奋性增加有关，表现为阈强度显著降低，以及通过去极化电流注射评估的刺激反应函数斜率增加。兴奋性的增加与动作电位下降速率和动作电位后超极化持续时间的显著降低有关。这些兴奋性和动作电位波形的变化与电压门控钾电流激活的电压依赖性和稳态可用性的显著变化以及稳态失活的电压门控钾电流密度的显著降低有关。这些数据表明，钾通道亚型可能为治疗炎症性肌肉疼痛提供新的靶点。这些结果也支持了这样的假设，即身体特定区域产生疼痛的潜在机制是独特的，这表明即使不是必须，用特定的治疗干预措施治疗源自身体不同部位的疼痛也可能是可行的。
