The majority of myelinated and unmyelinated sensory nerve fibers that innervate bone express the tropomyosin receptor kinase A.
The majority of myelinated and unmyelinated sensory nerve fibers that innervate bone express the tropomyosin receptor kinase A.
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DOI：
10.1016/j.neuroscience.2011.01.039
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发表时间：
2011-03-31
期刊：
影响因子：
3.3
通讯作者：
Mantyh PW
中科院分区：
文献类型：
--
作者：
Castañeda-Corral G;Jimenez-Andrade JM;Bloom AP;Taylor RN;Mantyh WG;Kaczmarska MJ;Ghilardi JR;Mantyh PW
虽然骨骼疼痛是慢性疼痛和残疾的主要原因，但对支配骨骼的特定神经纤维群知之甚少。最近的研究报道，阻断神经生长因子（NGF）或其同源受体，原肌球蛋白受体激酶A（TrkA）的治疗是有效的减轻骨骼疼痛。当评估在疼痛状态中靶向NGF-TrkA信号传导的镇痛功效时要考虑的潜在因素是神经支配疼痛所产生的组织的NGF响应性TrkA+伤害感受器的分数，因为这种神经支配和靶向NGF-TrkA信号传导的镇痛功效可以在组织与组织之间显著变化。为了探讨这一点，在骨骼，组织切片和整个安装准备的正常，成年小鼠股骨进行了分析，使用免疫组织化学和共聚焦显微镜。对这些制备物的分析显示，表达降钙素基因相关肽（CGRP）并支配骨膜、矿化骨和骨髓的80%的无髓鞘/薄髓鞘感觉神经纤维也表达TrkA。类似地，大多数表达神经丝200 kDa（NF 200）的有髓鞘感觉神经纤维也共表达TrkA，神经丝200 kDa支配骨膜、矿化骨和骨髓。在正常股骨中，单位体积内CGRP+、NF 200+和TrkA+感觉神经纤维的相对密度为：骨膜>骨髓>矿化骨>软骨，各自的相对密度为100：2：0.1：0。支配骨骼的大多数感觉神经纤维表达TrkA+的观察结果可以部分解释为什么阻断NGF/TrkA通路的疗法在减轻骨骼疼痛方面非常有效。
Although skeletal pain is a leading cause of chronic pain and disability, relatively little is known about the specific populations of nerve fibers that innervate the skeleton. Recent studies have reported that therapies blocking nerve growth factor (NGF) or its cognate receptor, tropomyosin receptor kinase A (TrkA) are efficacious in attenuating skeletal pain. A potential factor to consider when assessing the analgesic efficacy of targeting NGF-TrkA signaling in a pain state is the fraction of NGF-responsive TrkA+ nociceptors that innervate the tissue from which the pain is arising, as this innervation and the analgesic efficacy of targeting NGF-TrkA signaling may vary considerably from tissue to tissue. To explore this in the skeleton, tissue slices and whole mount preparations of the normal, adult mouse femur were analyzed using immunohistochemistry and confocal microscopy. Analysis of these preparations revealed that 80% of the unmyelinated/thinly myelinated sensory nerve fibers that express calcitonin gene-related peptide (CGRP) and innervate the periosteum, mineralized bone and bone marrow also express TrkA. Similarly, the majority of myelinated sensory nerve fibers that express neurofilament 200 kDa (NF200) which innervate the periosteum, mineralized bone and bone marrow also co-express TrkA. In the normal femur, the relative density of CGRP+, NF200+ and TrkA+ sensory nerve fibers per unit volume is: periosteum > bone marrow > mineralized bone > cartilage with the respective relative densities being 100: 2: 0.1: 0. The observation that the majority of sensory nerve fibers innervating the skeleton express TrkA+, may in part explain why therapies that block NGF/TrkA pathway are highly efficacious in attenuating skeletal pain.
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10.1073/pnas.0508005103
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