Nencini Sara, Ivanusic Jason J
Department of Anatomy and Neuroscience, University of Melbourne Melbourne, VIC, Australia.
Front Physiol. 2016 Apr 26;7:157. doi: 10.3389/fphys.2016.00157. eCollection 2016.
Pain is associated with most bony pathologies. Clinical and experimental observations suggest that bone pain can be derived from noxious stimulation of the periosteum or bone marrow. Sensory neurons are known to innervate the periosteum and marrow cavity, and most of these have a morphology and molecular phenotype consistent with a role in nociception. However, little is known about the physiology of these neurons, and therefore information about mechanisms that generate and maintain bone pain is lacking. The periosteum has received greater attention relative to the bone marrow, reflecting the easier access of the periosteum for experimental assessment. With the electrophysiological preparations used, investigators have been able to record from single periosteal units in isolation, and there is a lot of information available about how they respond to different stimuli, including those that are noxious. In contrast, preparations used to study sensory neurons that innervate the bone marrow have been limited to recording multi-unit activity in whole nerves, and whilst they clearly report responses to noxious stimulation, it is not possible to define responses for single sensory neurons that innervate the bone marrow. There is only limited evidence that peripheral sensory neurons that innervate bone can be sensitized or that they can be activated by multiple stimulus types, and at present this only exists in part for periosteal units. In the central nervous system, it is clear that spinal dorsal horn neurons can be activated by noxious stimuli applied to bone. Some can be sensitized under pathological conditions and may contribute in part to secondary or referred pain associated with bony pathology. Activity related to stimulation of sensory nerves that innervate bone has also been reported in neurons of the spinoparabrachial pathway and the somatosensory cortices, both known for roles in coding information about pain. Whilst these provide some clues as to the way information about bone pain is centrally coded, they need to be expanded to further our understanding of other central territories involved. There is a lot more to learn about the physiology of peripheral sensory neurons that innervate bone and their central projections.
疼痛与大多数骨病理状况相关。临床和实验观察表明，骨痛可能源于对骨膜或骨髓的伤害性刺激。已知感觉神经元支配骨膜和骨髓腔，其中大多数的形态和分子表型与伤害感受功能相符。然而，对于这些神经元的生理学特性了解甚少，因此缺乏关于产生和维持骨痛机制的信息。相对于骨髓，骨膜受到了更多关注，这反映出骨膜更便于进行实验评估。使用现有的电生理制备方法，研究人员能够单独记录单个骨膜单位的活动，并且有大量关于它们如何对不同刺激（包括伤害性刺激）做出反应的信息。相比之下，用于研究支配骨髓的感觉神经元的制备方法仅限于记录整条神经中的多单位活动，虽然它们能清楚地报告对伤害性刺激的反应，但无法确定支配骨髓的单个感觉神经元的反应。仅有有限的证据表明，支配骨骼的外周感觉神经元会被致敏，或者它们能被多种刺激类型激活，目前这仅部分适用于骨膜单位。在中枢神经系统中，很明显，施加于骨骼的伤害性刺激可激活脊髓背角神经元。有些神经元在病理条件下会被致敏，可能部分导致与骨病理相关的继发性或牵涉痛。在脊髓臂旁通路和躯体感觉皮层的神经元中也报告了与支配骨骼的感觉神经刺激相关的活动，这两个区域都在疼痛信息编码中发挥作用。虽然这些为骨痛信息在中枢的编码方式提供了一些线索，但需要进一步扩展研究，以加深我们对其他相关中枢区域的理解。关于支配骨骼的外周感觉神经元及其中枢投射的生理学特性，还有很多有待了解。
