Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
Eur J Pain. 2019 Feb;23(2):397-409. doi: 10.1002/ejp.1315. Epub 2018 Oct 11.
Pathologies that affect the bone marrow have a significant inflammatory component; however, it is not clear how inflammatory mediators affect nociceptive nerve terminals within the marrow cavity.
In this study, an in vivo bone-nerve preparation was used to directly record the physiological response properties of bone marrow nociceptors innervating the tibial marrow cavity of rats, before and after application of the inflammatory agent carrageenan. In addition, endogenous artemin was sequestered by application of an artemin neutralizing antibody to determine if this could prevent the inflammation-induced physiological changes observed.
A single injection of carrageenan administered into the tibial marrow cavity produced rapid changes in weight bearing (pain-like behaviour) in conscious animals. Carrageenan, but not saline, activated bone marrow nociceptors in whole-nerve recordings and sensitized a subtype of Aδ-bone marrow nociceptors to mechanical stimulation. The activation and sensitization had a rapid time course that matched that of pain-like behaviours. Sequestration of endogenous artemin significantly reduced carrageenan-induced increases in ongoing activity and completely abolished sensitization of bone marrow nociceptors to mechanical stimulation.
These observations indicate that inflammation affects the activity and sensitivity of bone marrow nociceptors; that artemin plays a role in these changes; and that artemin might be a promising target for pharmacological manipulations in the treatment of inflammatory bone pain.
Most pathologies that affect the bone marrow have an inflammatory component. We have used a model of carrageenan-induced inflammation to show that sequestration of artemin reduces inflammation-induced activation and sensitization of bone marrow nociceptors. Our findings suggest that artemin signalling is a target for the treatment of inflammatory bone pain.
影响骨髓的病变具有显著的炎症成分；然而，炎症介质如何影响骨髓腔内的伤害性神经末梢尚不清楚。
在这项研究中，使用体内骨神经制备物直接记录支配大鼠胫骨骨髓腔的骨髓伤害感受器的生理反应特性，在应用炎症剂角叉菜胶之前和之后。此外，应用 artemin 中和抗体来隔离内源性 artemin，以确定这是否可以防止观察到的炎症引起的生理变化。
单次注射到胫骨骨髓腔中的角叉菜胶在清醒动物中迅速引起负重变化（疼痛样行为）。角叉菜胶而不是生理盐水，在全神经记录中激活了骨髓伤害感受器，并使 Aδ-骨髓伤害感受器对机械刺激敏感。激活和敏化具有与疼痛样行为相匹配的快速时程。内源性 artemin 的隔离显著降低了角叉菜胶诱导的持续活动增加，并完全消除了骨髓伤害感受器对机械刺激的敏化。
这些观察表明炎症影响骨髓伤害感受器的活性和敏感性；artemin 在这些变化中起作用；并且 artemin 可能是治疗炎症性骨痛的药理学干预的有希望的靶点。
大多数影响骨髓的病变都有炎症成分。我们使用角叉菜胶诱导的炎症模型表明，artemin 隔离减少了炎症诱导的骨髓伤害感受器的激活和敏化。我们的发现表明，artemin 信号是治疗炎症性骨痛的靶点。
