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使用电生理学比较骨关节炎临床前模型中的伤害感受器特性。

Comparison of nociceptor properties using electrophysiology in preclinical models of osteoarthritis.

机构信息

Departments of Pharmacology and Anaesthesia, Pain Management & Perioperative Medicine, Dalhousie University, 5850 College Street, Halifax, Nova Scotia, B3H 4R2, Canada.

出版信息

Neurosci Lett. 2024 Sep 25;840:137950. doi: 10.1016/j.neulet.2024.137950. Epub 2024 Aug 23.

Abstract

Osteoarthritis (OA) pain originates in the joint by sensitization of articular nociceptors. While behavioural assessments provide valuable information regarding pain symptoms, the techniques are subjective and open to interpretation by the experimenter. This study used in vivo electrophysiological approaches to measure objectively joint nociceptor properties in three rodent models of OA. Single unit extracellular recordings of joint mechanosensitive afferents were carried out in male and female rats following either (1) transection of the medial meniscus (MMT: post-traumatic OA), (2) intra-articular injection of sodium monoiodoacetate (MIA: chemically-induced OA), or (3) intra-articular injection of lysophosphatidic acid (LPA: neuropathic OA). In naïve male control rats, the mechanical threshold of joint mechanonociceptors (23.5 ± 1.8 mNm) was significantly reduced with MMT (9.4 ± 1.1 mNm) and MIA (15.1 ± 1.6 mNm). In females, the mechanical threshold of naïve rats (23.2 ± 3.1 mNm) was reduced following induction of MMT (8.3 ± 1.0 mNm) and LPA (10.6 ± 2.2 mNm). Afferent firing frequency increased in male MMT (∼275 %), LPA (∼175 %), MIA (225 %), and female MMT (∼146 %), LPA (∼200 %), and MIA (∼192 %). Mechanical threshold and evoked firing were negatively correlated in all models for both sexes except LPA rats (male + female) and female MMT. These data indicate that MMT, MIA, and LPA induce peripheral sensitization of joint afferents thereby validating their use in OA pain studies.

摘要

骨关节炎 (OA) 疼痛源于关节,关节伤害感受器敏化。虽然行为评估提供了有关疼痛症状的有价值的信息,但这些技术是主观的,容易受到实验者的解释。本研究使用体内电生理方法测量三种 OA 啮齿动物模型中关节伤害感受器的特性。在雄性和雌性大鼠中,在以下情况下进行关节机械敏感传入神经的单个单位细胞外记录:(1) 内侧半月板 (MMT) 横断 (创伤后 OA),(2) 关节内注射单碘乙酸钠 (MIA:化学诱导性 OA),或 (3) 关节内注射溶血磷脂酸 (LPA:神经病理性 OA)。在未处理的雄性对照大鼠中,关节机械伤害感受器的机械阈值 (23.5 ± 1.8 mNm) 显著降低,MMT (9.4 ± 1.1 mNm) 和 MIA (15.1 ± 1.6 mNm)。在雌性中,未处理的大鼠的机械阈值 (23.2 ± 3.1 mNm) 在 MMT (8.3 ± 1.0 mNm) 和 LPA (10.6 ± 2.2 mNm) 诱导后降低。在雄性 MMT (∼275%)、LPA (∼175%)、MIA (225%) 和雌性 MMT (∼146%)、LPA (∼200%) 和 MIA (∼192%) 中,传入神经的放电频率增加。除了 LPA 大鼠 (雄性+雌性) 和雌性 MMT 之外,在所有模型中,机械阈值和诱发放电之间呈负相关。这些数据表明,MMT、MIA 和 LPA 诱导关节传入神经的外周敏化,从而验证了它们在 OA 疼痛研究中的应用。

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