Mense S
Department of Anatomy and Cell Biology III, Heidelberg University, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.
Exp Brain Res. 2009 Jun;196(1):89-100. doi: 10.1007/s00221-008-1674-4. Epub 2009 Jan 13.
Morphologically, muscle nociceptors are free nerve endings connected to the CNS by thin myelinated (group III) or unmyelinated (group IV) afferent fibers. Not all of these endings are nociceptive; approximately 40% have a low mechanical threshold and likely fulfill non-nociceptive functions. Two chemical stimuli are particularly relevant as causes of muscle pain. The first is a drop in tissue pH, i.e. an increase in proton (H+) concentration. A large number of painful patho(physio)logical alterations of muscle tissue are associated with an acidic interstitial pH (e.g. tonic contractions, spasm, inflammation). The second important cause of muscle pain is a release of adenosine triphosphate (ATP). ATP is present in all body cells, but in muscle its concentration is particularly high. Any damage of muscle cells (trauma, necrotic myositis) is accompanied by a release of ATP from the cells. Therefore, ATP is considered a general pain stimulus by some. ATP and protons are relatively specific stimuli for muscle pain; in cutaneous pain they play a less important role. The numerous agents that are released in pathologically altered muscle include substances that desensitize mechanosensitive group IV receptors. Capsaicin has a long-lasting desensitizing action, brain-derived neurotrophic factor, and tumor necrosis factor-alpha, a short-lasting one. Most of the agents exciting group IV units (e.g. low pH, ATP, capsaicin) activate not only nociceptive endings but also non-nociceptive ones. The only substance encountered that excites exclusively nociceptive group IV receptors is nerve growth factor (NGF). In rat muscle chronically inflamed with complete Freund's adjuvant, most group IV endings are sensitized to mechanical (and to some) chemical stimuli. However, stimulants such as ATP, NGF, and solutions of low pH were found to be less effective in inflamed muscle. A possible explanation for this surprising finding is that in inflamed muscle the concentrations of ATP and NGF and H+ are increased. Therefore, experimental administration of these agents is a less effective stimulus.
在形态学上，肌肉伤害感受器是通过细有髓鞘（III组）或无髓鞘（IV组）传入纤维与中枢神经系统相连的游离神经末梢。并非所有这些末梢都是伤害性的；大约40%具有低机械阈值，可能履行非伤害性功能。有两种化学刺激作为肌肉疼痛的原因特别相关。第一种是组织pH值下降，即质子（H+）浓度增加。肌肉组织的大量疼痛性病理（生理）改变与酸性间质pH值相关（例如强直性收缩、痉挛、炎症）。肌肉疼痛的第二个重要原因是三磷酸腺苷（ATP）的释放。ATP存在于所有体细胞中，但在肌肉中其浓度特别高。肌肉细胞的任何损伤（创伤、坏死性肌炎）都会伴随着ATP从细胞中释放。因此，ATP被一些人认为是一种普遍的疼痛刺激物。ATP和质子是肌肉疼痛相对特异性的刺激物；在皮肤疼痛中它们起的作用较小。在病理改变的肌肉中释放的众多因子包括使机械敏感的IV组受体脱敏的物质。辣椒素具有持久的脱敏作用，脑源性神经营养因子和肿瘤坏死因子-α具有短暂的脱敏作用。大多数刺激IV组单位的因子（例如低pH值、ATP、辣椒素）不仅激活伤害性末梢，也激活非伤害性末梢。唯一遇到的专门刺激伤害性IV组受体的物质是神经生长因子（NGF）。在用完全弗氏佐剂慢性炎症的大鼠肌肉中，大多数IV组末梢对机械（和一些）化学刺激敏感。然而，发现ATP、NGF和低pH值溶液等刺激物在炎症肌肉中效果较差。对这一惊人发现可能的解释是，在炎症肌肉中ATP、NGF和H+的浓度增加。因此，实验性给予这些因子是一种效果较差的刺激。
