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P2X3 receptors contribute to muscle pain induced by static contraction by a mechanism dependent on neutrophil migration.
Purinergic Signalling ( IF 3.0 ) Pub Date : 2019-05-21 , DOI: 10.1007/s11302-019-09659-0
Bruna de Melo Aquino 1 , Diogo Francisco da Silva Dos Santos 1 , Carolina Ocanha Jorge 1 , Aline Carolina Salgado Marques 1 , Juliana Maia Teixeira 2 , Carlos Amilcar Parada 2 , Maria Claudia Goncalves Oliveira-Fusaro 1
Affiliation  

P2X3 receptors are involved with several pain conditions. Muscle pain induced by static contraction has an important socioeconomic impact. Here, we evaluated the involvement of P2X3 receptors on mechanical muscle hyperalgesia and neutrophil migration induced by static contraction in rats. Also, we evaluated whether static contraction would be able to increase muscle levels of TNF-α and IL-1β. Male Wistar rats were pretreated with the selective P2X3 receptor antagonist, A-317491, by intramuscular or intrathecal injection and the static contraction-induced mechanical muscle hyperalgesia was evaluated using the Randall–Selitto test. Neutrophil migration was evaluated by measurement of myeloperoxidase (MPO) kinetic–colorimetric assay and the cytokines TNF-α and IL-1β by enzyme-linked immunosorbent assay. Intramuscular or intrathecal pretreatment with A-317491 prevented static contraction-induced mechanical muscle hyperalgesia. In addition, A-317491 reduced static contraction-induced mechanical muscle hyperalgesia when administered 30 and 60 min of the beginning of static contraction, but not after 30 and 60 min of the end of static contraction. Intramuscular A-317491 also prevented static contraction-induced neutrophil migration. In a period of 24 h, static contraction did not increase muscle levels of TNF-α and IL-1β. These findings demonstrated that mechanical muscle hyperalgesia and neutrophil migration induced by static contraction are modulated by P2X3 receptors expressed on the gastrocnemius muscle and spinal cord dorsal horn. Also, we suggest that P2X3 receptors are important to the development but not to maintenance of muscle hyperalgesia. Therefore, P2X3 receptors can be pointed out as a target to musculoskeletal pain conditions induced by daily or work-related activities.

中文翻译:

P2X3受体通过依赖于嗜中性粒细胞迁移的机制导致静态收缩引起的肌肉疼痛。

P2X3受体涉及多种疼痛状况。静态收缩引起的肌肉疼痛具有重要的社会经济影响。在这里,我们评估了P2X3受体参与大鼠的静态收缩引起的机械性肌肉痛觉过敏和中性粒细胞迁移。此外,我们评估了静态收缩是否能够增加肌肉中TNF-α和IL-1β的水平。雄性Wistar大鼠通过肌肉内或鞘内注射用选择性P2X3受体拮抗剂A-317491进行了预处理,并使用Randall-Selitto测试评估了静态收缩引起的机械性肌肉痛觉过敏。通过测量髓过氧化物酶(MPO)动力学比色法以及通过酶联免疫吸附法测定细胞因子TNF-α和IL-1β来评估中性粒细胞的迁移。用A-317491进行肌内或鞘内预处理可防止静态收缩引起的机械性肌肉痛觉过敏。此外,A-317491在静态收缩开始30和60分钟时(但在静态收缩结束30和60分钟后)给药时,可减少静态收缩引起的机械性肌肉痛觉过敏。肌内A-317491还阻止了静态收缩诱导的中性粒细胞迁移。在24小时内,静态收缩并没有增加TNF-α和IL-1β的肌肉水平。这些发现表明,由机械收缩引起的机械性痛觉过敏和中性粒细胞迁移受腓肠肌和脊髓背角表达的P2X3受体调节。此外,我们建议P2X3受体对肌肉的痛觉过敏的发展很重要,但对维持皮肤痛觉过敏却不重要。
更新日期:2019-05-21
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