Klafke J Z, da Silva M A, Rossato M F, de Prá S Dal Toé, Rigo F K, Walker C I B, Bochi G V, Moresco R N, Ferreira J, Trevisan G
Grupo Multidisciplinar de Saúde, Programa de Pós-Graduação em Atenção Integral à Saúde, Universidade de Cruz Alta (UNICRUZ), 98020-290, Cruz Alta, RS, Brazil.
Departamento de Saúde, Curso de Biomedicina, Faculdade de Educação e Cultura de Vilhena, 76980-000, Vilhena, RO, Brazil.
Pflugers Arch. 2016 Feb;468(2):229-41. doi: 10.1007/s00424-015-1746-9. Epub 2015 Oct 21.
Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain.
1型复杂性区域疼痛综合征（CRPS1）可能由缺血/再灌注引发，导致难以治疗的急慢性疼痛。尽管如此，CRPS1的潜在机制尚未完全阐明。因此，本研究的目的是在慢性缺血后疼痛（CPIP）动物模型中评估炎症、氧化应激以及瞬时受体电位锚蛋白1（TRPA1）通道（一种炎症和氧化物质的化学感受器）的作用。雄性Wistar大鼠接受3小时后爪缺血/再灌注（CPIP模型）。在CPIP后1天（急性期）和14天（慢性期）评估不同的伤害感受、炎症、缺血和氧化应激参数。CPIP后还观察了TRPA1拮抗剂的作用和TRPA1免疫反应性。在CPIP急性期，我们观察到机械性和冷觉异常性疼痛；肿瘤坏死因子-α（后爪）、缺血修饰白蛋白（IMA）（血清）、蛋白质羰基（后爪和脊髓）、乳酸（血清）和4-羟基壬烯醛（4-HNE，后爪和脊髓）水平升高；以及更高的髓过氧化物酶（MPO）和N-乙酰-β-D-葡萄糖苷酶（NAGase）活性（后爪）。在CPIP慢性期，我们检测到机械性和冷觉异常性疼痛以及IMA（血清）、蛋白质羰基（后爪和脊髓）和4-HNE（后爪和脊髓）水平升高。TRPA1拮抗作用在CPIP后1天和14天减轻了机械性和冷觉异常性疼痛，但未观察到TRPA1免疫反应性的变化。CPIP的急性（炎症和氧化应激）和慢性（氧化应激）阶段存在不同的机制。TRPA1激活可能与CRPS1/CPIP诱导的急慢性疼痛相关。
