Department of Neural and Pain Sciences, School of Dentistry, Program in Neuroscience, Center to Advance Chronic Pain Research, The University of Maryland, Baltimore, MD, USA.
J Dent Res. 2020 Aug;99(9):1004-1012. doi: 10.1177/0022034520919384. Epub 2020 May 6.
Craniofacial muscle pain is highly prevalent in temporomandibular disorders but is difficult to treat. Enhanced understanding of neurobiology unique to craniofacial muscle pain should lead to the development of novel mechanism-based treatments. Herein, we review recent studies to summarize neural pathways of craniofacial muscle pain. Nociceptive afferents in craniofacial muscles are predominantly peptidergic afferents enriched with TRPV1. Signals from peripheral glutamate receptors converge onto TRPV1, leading to mechanical hyperalgesia. Further studies are needed to clarify whether hyperalgesic priming in nonpeptidergic afferents or repeated acid injections also affect craniofacial muscle pain. Within trigeminal ganglia, afferents innervating craniofacial muscles interact with surrounding satellite glia, which enhances the sensitivity of the inflamed neurons as well as nearby uninjured afferents, resulting in hyperalgesia and ectopic pain originating from adjacent orofacial tissues. Craniofacial muscle afferents project to a wide area within the trigeminal nucleus complex, and central sensitization of medullary dorsal horn neurons is a critical factor in muscle hyperalgesia related to ectopic pain and emotional stress. Second-order neurons project rostrally to pathways associated with affective pain, such as parabrachial nucleus and medial thalamic nucleus, as well as sensory-discriminative pain, such as ventral posteromedial thalamic nuclei. Abnormal endogenous pain modulation can also contribute to chronic muscle pain. Descending serotonergic circuits from the rostral ventromedial medulla facilitate activation of second-order neurons in the trigeminal nucleus complex, which leads to the maintenance of mechanical hyperalgesia of inflamed masseter muscle. Patients with temporomandibular disorders exhibit altered brain networks in widespread cortical and subcortical regions. Recent development of methods for neural circuit manipulation allows silencing of specific hyperactive neural circuits. Chemogenetic silencing of TRPV1-expressing afferents or rostral ventromedial medulla neurons attenuates hyperalgesia during masseter inflammation. It is likely, therefore, that further delineation of neural circuits mediating craniofacial muscle hyperalgesia potentially enhances treatment of chronic muscle pain conditions.
颅面部肌肉疼痛在颞下颌关节紊乱中非常普遍，但难以治疗。增强对颅面部肌肉疼痛特有的神经生物学的理解，应能开发出针对新机制的治疗方法。本文综述了最近的研究，以总结颅面部肌肉疼痛的神经通路。颅面部肌肉中的伤害性传入主要是富含 TRPV1 的肽能传入。来自外周谷氨酸受体的信号汇集到 TRPV1 上，导致机械性痛觉过敏。需要进一步的研究来阐明非肽能传入的痛觉过敏启动或重复酸注射是否也会影响颅面部肌肉疼痛。在三叉神经节中，支配颅面部肌肉的传入与周围卫星胶质细胞相互作用，增强了炎症神经元以及附近未受伤传入的敏感性，导致源自相邻口面组织的痛觉过敏和异位疼痛。颅面部肌肉传入投射到三叉神经核复合体的广泛区域，延髓背角神经元的中枢敏化是与异位疼痛和情绪应激相关的肌肉痛觉过敏的关键因素。二级神经元向与情感疼痛相关的通路（如臂旁核和内侧丘脑核）以及与感觉辨别疼痛相关的通路（如腹后内侧丘脑核）向头侧投射。异常的内源性疼痛调节也可能导致慢性肌肉疼痛。来自延髓头端腹内侧的 5-羟色胺能下行通路促进三叉神经核复合体中二级神经元的激活，导致炎症咬肌的机械性痛觉过敏维持。颞下颌关节紊乱患者在广泛的皮质和皮质下区域表现出改变的大脑网络。最近神经回路操作方法的发展允许对特定的过度活跃神经回路进行沉默。TRPV1 表达传入的化学遗传沉默或延髓头端腹内侧神经元可减轻咬肌炎症期间的痛觉过敏。因此，进一步描绘介导颅面部肌肉痛觉过敏的神经回路可能会增强对慢性肌肉疼痛状况的治疗。
