Michael G DeGroote Institute for Pain Research and Care, McMaster University, 1200 Main Street West, HSC 4N35, Hamilton ON, L8N 3Z5, Canada.
Mol Pain. 2009 Sep 28;5:57. doi: 10.1186/1744-8069-5-57.
Clinical data on osteoarthritis (OA) suggest widespread changes in sensory function that vary during the progression of OA. In previous studies on a surgically-induced animal model of OA we have observed that changes in structure and gene expression follow a variable trajectory over the initial days and weeks. To investigate mechanisms underlying changes in sensory function in this model, the present electrophysiological study compared properties of primary sensory nociceptive neurons at one and two months after model induction with properties in naïve control animals. Pilot data indicated no difference in C- or Adelta-fiber associated neurons and therefore the focus is on Abeta-fiber nociceptive neurons.
At one month after unilateral derangement of the knee by cutting the anterior cruciate ligament and removing the medial meniscus, the only changes observed in Abeta-fiber dorsal root ganglion (DRG) neurons were in nociceptor-like unresponsive neurons bearing a hump on the repolarization phase; these changes consisted of longer half width, reflecting slowed dynamics of AP genesis, a depolarized Vm and an increased AP amplitude. At two months, changes observed were in Abeta-fiber high threshold mechanoreceptors, which exhibited shorter AP duration at base and half width, shorter rise time and fall time, and faster maximum rising rate/maximum falling rate, reflecting accelerated dynamics of AP genesis.
These data indicate that Abeta nociceptive neurons undergo significant changes that vary in time and occur later than changes in structure and in nociceptive scores in this surgically induced OA model. Thus, if changes in Abeta-fiber nociceptive neurons in this model reflect a role in OA pain, they may relate to mechanisms underlying pain associated with advanced OA.
有关骨关节炎（OA）的临床数据表明，感觉功能广泛改变，且在 OA 进展过程中发生变化。在以前的关于手术诱导的 OA 动物模型的研究中，我们观察到结构和基因表达的变化在最初几天和几周内呈现出不同的轨迹。为了研究该模型中感觉功能变化的机制，本电生理学研究比较了模型诱导后 1 个月和 2 个月时初级感觉伤害性神经元的特性与未处理对照动物的特性。初步数据表明 C 纤维或 Aδ纤维相关神经元没有差异，因此研究重点是 Aβ纤维伤害性神经元。
在膝关节通过切断前交叉韧带和切除内侧半月板而单侧紊乱后 1 个月，在 Aβ纤维背根神经节（DRG）神经元中观察到的唯一变化是在伤害感受器样无反应神经元中，在复极相上出现驼峰；这些变化包括更长的半宽度，反映了 AP 产生的动力学减慢，Vm 去极化和 AP 幅度增加。在 2 个月时，观察到的变化是 Aβ纤维高阈值机械感受器，其在基值和半宽度处的 AP 持续时间更短，上升时间和下降时间更短，最大上升率/最大下降率更快，反映了 AP 产生的动力学加快。
这些数据表明，Aβ伤害性神经元发生了显著变化，其时间变化与结构变化和该手术诱导的 OA 模型中的伤害性评分变化不同。因此，如果该模型中 Aβ纤维伤害性神经元的变化反映了 OA 疼痛的作用，它们可能与晚期 OA 相关疼痛的机制有关。
