Adães S, Ferreira-Gomes J, Mendonça M, Almeida L, Castro-Lopes J M, Neto F L
Departamento de Biologia Experimental, Centro de Investigação Médica da Faculdade de Medicina da Universidade do Porto (CIM-FMUP), Alameda Prof Hernâni Monteiro, 4200-319 Porto, Portugal; Morphysiology of the Somatosensory System Group, Instituto de Biologia Molecular e Celular (IBMC), Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
Departamento de Biologia Experimental, Centro de Investigação Médica da Faculdade de Medicina da Universidade do Porto (CIM-FMUP), Alameda Prof Hernâni Monteiro, 4200-319 Porto, Portugal; Morphysiology of the Somatosensory System Group, Instituto de Biologia Molecular e Celular (IBMC), Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
Osteoarthritis Cartilage. 2015 Jun;23(6):914-24. doi: 10.1016/j.joca.2015.02.010. Epub 2015 Feb 18.
Pain exacerbated by movement and loading on the joint is the major symptom of osteoarthritis (OA), but the mechanisms of chronic pain in this pathology are still poorly understood. Using the intra-articular (i.a.) injection of collagenase in the knee of rats as a model of OA, we aimed at evaluating whether injury of sensory neurons may contribute to the development of OA-associated nociception.
OA was induced by i.a. injection of collagenase into the left knee joint of adult male Wistar rats. Histopathological changes and movement and loading-induced nociception were assessed for 6 weeks. A time-course analysis of the expression of the neuronal injury markers activating transcription factor-3 (ATF-3) and neuropeptide Y (NPY) and of the neuropeptide SP in the dorsal root ganglion (DRG) was performed. Gabapentin's effect on nociception was evaluated, as well as the expression of the α2δ-1 voltage-gated calcium channel subunit.
Collagenase induced the development of OA-like histopathological changes and of movement-induced nociception. Altered expression of ATF-3, NPY and SP was observed in the DRG, correlating with the degree of articular degeneration after 6 weeks of disease progression. Repeated administration of gabapentin reversed the nociceptive responses 6 weeks after the induction of OA. α2δ-1 was upregulated in the DRG.
By inducing nociceptive behaviours associated with relevant joint structural changes, the i.a. injection of collagenase presents itself as a pertinent model for the study of OA pain. The findings in this study support the hypothesis that injury of sensory neurons innervating OA joints may be a significant element in the mechanisms of OA-associated pain.
运动和关节负重时疼痛加剧是骨关节炎（OA）的主要症状，但该病理过程中慢性疼痛的机制仍知之甚少。我们以向大鼠膝关节内注射胶原酶作为OA模型，旨在评估感觉神经元损伤是否会导致OA相关伤害感受的发展。
通过向成年雄性Wistar大鼠的左膝关节内注射胶原酶诱导OA。评估6周内的组织病理学变化以及运动和负重诱导的伤害感受。对背根神经节（DRG）中神经元损伤标志物激活转录因子-3（ATF-3）、神经肽Y（NPY）和神经肽P物质（SP）进行时间进程分析。评估加巴喷丁对伤害感受的影响以及α2δ-1电压门控钙通道亚单位的表达。
胶原酶诱导了OA样组织病理学变化和运动诱导的伤害感受。在DRG中观察到ATF-3、NPY和SP的表达改变，与疾病进展6周后的关节退变程度相关。OA诱导6周后，重复给予加巴喷丁可逆转伤害性反应。DRG中α2δ-1上调。
通过诱导与相关关节结构变化相关的伤害性行为，膝关节内注射胶原酶是研究OA疼痛的一个相关模型。本研究结果支持以下假设：支配OA关节的感觉神经元损伤可能是OA相关疼痛机制中的一个重要因素。
