School of Physiology and Pharmacology, Medical Sciences Building, University of Bristol, BS8 1TD, UK.
Osteoarthritis Cartilage. 2012 Apr;20(4):305-13. doi: 10.1016/j.joca.2012.01.002. Epub 2012 Jan 10.
Osteoarthritis (OA) pain mechanisms are poorly understood. We used the monosodium iodoacetate (MIA) model of knee OA to characterize changes in excitability during the course of OA in different classes of mechanosensitive afferents projecting to joint-associated tissues, and examine whether these afferent responses and pain behavior are correlated.
Rats were injected intra-articularly with MIA (1mg in 50 μl). Hind-limb weight bearing was studied 3 (MIA3) and 14 (MIA14) days after MIA, followed by deep anesthesia and teased-nerve-fiber recordings. Spontaneous activity (SA) and mechanically evoked responses of A- and C-mechanosensitive fibers (AM and CM respectively, probably nociceptive) innervating tissues associated with the ipsilateral knee joint were examined.
MIA3 and MIA14 rats exhibited reduced ipsilateral weight bearing. SA (>0.02 impulses/s) occurred in ∼50% of CMs from MIA rats vs 0% in normals. SA firing rates in CMs were significantly higher than normal; decreased weight bearing was correlated with increased CM SA rates. Neither percentages of AMs with SA (20%) nor their firing rates (0-0.01 impulses/s) significantly increased after MIA. In contrast, in MIA rats AMs, but not CMs, exhibited decreased mechanical thresholds and increased firing rates in response to suprathreshold mechanical stimulation.
These findings of increased SA firing rate in CMs but not AMs and increased mechanical sensitivity of AMs, but not CMs, have not previously been reported. These are two distinct important physiological mechanisms that may underpin spontaneous pain (CMs) and stimulus-evoked pain (AMs) in OA. Our data contribute to a mechanism-based understanding of OA pain.
骨关节炎（OA）的疼痛机制尚不清楚。我们使用膝骨关节炎的碘乙酸单钠（MIA）模型，在不同类别的机械敏感传入纤维投射到关节相关组织的 OA 过程中，描述兴奋性变化，并检查这些传入反应和疼痛行为是否相关。
将 MIA（1mg 于 50μl 中）关节内注射到大鼠体内。在 MIA 后 3 天（MIA3）和 14 天（MIA14）测量后肢负重情况，然后进行深麻醉和 teased-nerve-fiber 记录。检测支配同侧膝关节相关组织的 A-和 C-机械敏感纤维（分别为 AM 和 CM，可能是伤害性）的自发性活动（SA）和机械诱发反应。
MIA3 和 MIA14 大鼠表现出对侧负重减少。与正常大鼠相比，MIA 大鼠中约 50%的 CM 出现 SA（>0.02 脉冲/s）。CM 的 SA 放电率明显高于正常水平；减少的负重与 CM SA 率的增加相关。SA 发生的 AM 百分比（20%）和它们的放电率（0-0.01 脉冲/s）在 MIA 后均无明显增加。相比之下，在 MIA 大鼠中，AM 而不是 CM，表现出机械阈值降低和对超阈值机械刺激的放电率增加。
CM 中 SA 放电率增加而 AM 中 SA 放电率不增加，以及 AM 的机械敏感性增加而 CM 不增加，这些发现以前没有报道过。这些是两种不同的重要生理机制，可能是 OA 自发性疼痛（CM）和刺激诱发疼痛（AM）的基础。我们的数据有助于对 OA 疼痛的基于机制的理解。
