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泛连接蛋白通道1、P2×7受体和二甲基亚砜介导斑马鱼的疼痛反应。

Pannexin channel 1, P2×7 receptors, and Dimethyl Sulfoxide mediate pain responses in zebrafish.

作者信息

Gusso Darlan, Cruz Fernanda Fernandes, Fritsch Pâmella Moreira, Gobbo Marília Oberto, Morrone Fernanda Bueno, Bonan Carla Denise

机构信息

Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Medicina e Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.

出版信息

Behav Brain Res. 2022 Apr 9;423:113786. doi: 10.1016/j.bbr.2022.113786. Epub 2022 Feb 3.

DOI:10.1016/j.bbr.2022.113786
PMID:35124136
Abstract

The zebrafish has been considered an ideal model for studies of complex behaviors since its behavioral repertoire is well described. Therefore, this study evaluated the perceived pain through behavioral changes in zebrafish larvae. Here we investigated the Acetic Acid (AA) effects on zebrafish larvae exposed in a short-time period (60 s) and the preventive effect from routinely used compounds, Dimethyl Sulfoxide (DMSO), Ethanol (EtOH), Ibuprofen (IBP), and Paracetamol (PAR). In addition, the effect of P2×7 antagonist, A740003, and pannexin channel 1 (PANX-1) inhibitor Probenecid (PROB) on AA-induced behavioral changes were evaluated. AA impaired the distance covered, acceleration, movement, and latency to the first entry in the center from 5 dpf exposed larvae. At 0.050% AA, PAR prevented alterations from the distance covered, acceleration, and movement. Surprisingly, 0.3% DMSO prevented behavioral changes induced by AA. However, the effects from 0.2% DMSO were not prominent. We used 0.2% DMSO as a PROB diluent. PROB prevented the changes in distance and movement observed at both AA concentrations (0.0025% and 0.05%) tested. Since EtOH had no analgesic properties, we used it as an A740003 vehicle to observe the analgesic effects of this compound. As noted, A740003 did not prevent the behavioral changes in the AA-induced pain model. In contrast, 0.2% DMSO and PROB prevented AA-induced behavioral changes. These data enforce that zebrafish could be used in translational studies since this species has behavioral responses related to pain in the early stages of development and responses to analgesics similar to observed in mammals.

摘要

由于斑马鱼的行为表现已得到充分描述,它被认为是研究复杂行为的理想模型。因此,本研究通过斑马鱼幼体的行为变化来评估其感知疼痛的情况。在此,我们研究了乙酸(AA)对短期(60秒)暴露的斑马鱼幼体的影响,以及常用化合物二甲基亚砜(DMSO)、乙醇(EtOH)、布洛芬(IBP)和对乙酰氨基酚(PAR)的预防作用。此外,还评估了P2×7拮抗剂A740003和泛连接蛋白通道1(PANX-1)抑制剂丙磺舒(PROB)对AA诱导的行为变化的影响。AA损害了5日龄暴露幼体的游动距离、加速度、活动以及首次进入中心区域的潜伏期。在0.050% AA浓度下,PAR可防止游动距离、加速度和活动的改变。令人惊讶的是,0.3% DMSO可防止AA诱导的行为变化。然而,0.2% DMSO的效果并不显著。我们使用0.2% DMSO作为PROB的稀释剂。PROB可防止在两种测试的AA浓度(0.0025%和0.05%)下观察到的距离和活动变化。由于EtOH没有镇痛特性,我们将其用作A740003的载体以观察该化合物的镇痛效果。如前所述,A740003不能预防AA诱导的疼痛模型中的行为变化。相比之下,0.2% DMSO和PROB可预防AA诱导的行为变化。这些数据表明斑马鱼可用于转化研究,因为该物种在发育早期具有与疼痛相关的行为反应,并且对镇痛药的反应与哺乳动物中观察到的相似。

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