Lysophosphatidic acid provides a missing link between osteoarthritis and joint neuropathic pain
Lysophosphatidic acid provides a missing link between osteoarthritis and joint neuropathic pain
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DOI：
10.1016/j.joca.2016.08.016
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发表时间：
2017-06-01
影响因子：
7
通讯作者：
Chambers, M. G.
中科院分区：
文献类型：
--
作者：
McDougall, J. J.;Albacete, S.;Chambers, M. G.
目的：越来越多的证据表明骨关节炎（OA）具有神经病变成分；然而，导致这种周围神经病变的分子的身份是未知的。本研究的目的是确定生物活性脂质溶血磷脂酸（LPA）对关节神经病变和疼痛的作用。设计：雄性Lewis大鼠膝关节关节内注射50 μ g LPA，并允许其恢复长达21天。通过电子显微图计算g-ratio评估隐神经髓鞘形成，通过激活转录因子-3 （ATF-3）表达可视化传入神经损伤。电生理法测定神经传导速度，后肢失电法测定关节疼痛。并对LPA拮抗剂Ki-16425的作用进行了评价。在OA单碘乙酸钠（MIA）模型中重复实验。结果：LPA引起关节神经脱髓鞘，导致神经传导速度下降。感觉神经元呈ATF-3阳性，动物表现为关节疼痛和膝关节损伤。mia治疗的大鼠也表现出脱髓鞘和伴随疼痛的关节神经病变的迹象。Ki-16425预处理可改善神经损伤和疼痛。结论：关节内注射LPA可引起膝关节神经病变、关节损伤和疼痛。药物阻断LPA受体可抑制关节神经损伤和后肢失能。因此，LPA是OA神经损伤发展和关节神经性疼痛起源的候选分子。(C) 2016国际骨关节炎研究学会。Elsevier Ltd.出版。版权所有。
Objective: Emerging evidence suggests that osteoarthritis (OA) has a neuropathic component; however, the identity of the molecules responsible for this peripheral neuropathy is unknown. The aim of this study was to determine the contribution of the bioactive lipid lysophosphatidic acid (LPA) to joint neuropathy and pain.Design: Male Lewis rats received an intra-articular injection of 50 mu g of LPA into the knee and allowed to recover for up to 21 days. Saphenous nerve myelination was assessed by g-ratio calculation from electron micrographs and afferent nerve damage visualised by activation transcription factor-3 (ATF-3) expression. Nerve conduction velocity was measured electrophysiologically and joint pain was determined by hindlimb incapacitance. The effect of the LPA antagonist Ki-16425 was also evaluated. Experiments were repeated in the sodium monoiodoacetate (MIA) model of OA.Results: LPA caused joint nerve demyelination which resulted in a drop in nerve conduction velocity. Sensory neurones were ATF-3 positive and animals exhibited joint pain and knee joint damage. MIA-treated rats also showed signs of demyelination and joint neuropathy with concomitant pain. Nerve damage and pain could be ameliorated by Ki-16425 pre-treatment.Conclusion: Intra-articular injection of LPA caused knee joint neuropathy, joint damage and pain. Pharmacological blockade of LPA receptors inhibited joint nerve damage and hindlimb incapacitance. Thus, LPA is a candidate molecule for the development of OA nerve damage and the origin of joint neuropathic pain. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.