Abstract:
The goals of this review are to improve understanding of the aetiology of chronic muscle pain and identify new targets for treatments. Muscle pain is usually associated with trigger points in syndromes such as fibromyalgia and myofascial syndrome, and with small spots associated with spontaneous electrical activity that seems to emanate from fibers inside muscle spindles in EMG studies. These observations, added to the reports that large-diameter primary afferents, such as those innervating muscle spindles, become hyperexcitable and develop spontaneous ectopic firing in conditions leading to neuropathic pain, suggest that changes in excitability of these afferents might make an important contribution to the development of pathological pain. Here, we review evidence that the muscle spindle afferents (MSAs) of the jaw-closing muscles become hyperexcitable in a model of chronic orofacial myalgia. In these afferents, as in other large-diameter primary afferents in dorsal root ganglia, firing emerges from fast membrane potential oscillations that are supported by a persistent sodium current (INaP ) mediated by Na+ channels containing the α-subunit NaV 1.6. The current flowing through NaV 1.6 channels increases when the extracellular Ca2+ concentration decreases, and studies have shown that INaP -driven firing is increased by S100β, an astrocytic protein that chelates Ca2+ when released in the extracellular space. We review evidence of how astrocytes, which are known to be activated in pain conditions, might, through their regulation of extracellular Ca2+ , contribute to the generation of ectopic firing in MSAs. To explain how ectopic firing in MSAs might cause pain, we review evidence supporting the hypothesis that cross-talk between proprioceptive and nociceptive pathways might occur in the periphery, within the spindle capsule.
摘要:
这篇综述的目的是提高对慢性肌肉疼痛病因的理解,并确定新的治疗目标。肌肉疼痛通常与纤维肌痛和肌筋膜综合征等综合征的触发点有关,在EMG研究中,与自发的电活动相关的小斑点似乎是从肌肉纺锤体内部的纤维发出的。这些观察,增加了大直径初级传入的报告,比如那些神经支配的肌肉纺锤,在导致神经性疼痛的条件下变得过度兴奋并发展自发性异位放电,表明这些传入者的兴奋性变化可能对病理性疼痛的发展做出重要贡献。这里,我们回顾了证据,证明在慢性口面部肌痛模型中,下颌闭合肌的肌梭传入(MSA)变得过度兴奋。在这些传入中,与背根神经节的其他大直径初级传入一样,放电是由快速的膜电位振荡产生的,该振荡由包含α亚基NaV1.6的Na通道介导的持续钠电流(INaP)支持。当细胞外Ca2+浓度降低时,流过NaV1.6通道的电流增加,研究表明,INaP驱动的点火增加了S100β,在细胞外空间释放时螯合Ca2+的星形胶质细胞蛋白。我们回顾了星形胶质细胞,已知在疼痛条件下被激活,可能,通过它们对细胞外Ca2+的调节,有助于MSA中异位激发的产生。为了解释MSA中的异位激发可能会导致疼痛,我们回顾了支持以下假设的证据:本体感受和伤害性途径之间的交叉对话可能发生在外围,在纺锤体胶囊内。