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局部应用一种 TRPA1 拮抗剂可减少大鼠创伤性肌肉损伤模型中的疼痛和炎症。

Topical application of a TRPA1 antagonist reduced nociception and inflammation in a model of traumatic muscle injury in rats.

机构信息

Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Avenida Roraima, 1000, Building 21, Room 5207, Santa Maria, RS, 97105-900, Brazil.

Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil.

出版信息

Inflammopharmacology. 2023 Dec;31(6):3153-3166. doi: 10.1007/s10787-023-01337-3. Epub 2023 Sep 27.


DOI:10.1007/s10787-023-01337-3
PMID:37752305
Abstract

Musculoskeletal pain is a widely experienced public healthcare issue, especially after traumatic muscle injury. Besides, it is a common cause of disability, but this pain remains poorly managed. However, the pathophysiology of traumatic muscle injury-associated pain and inflammation has not been fully elucidated. In this regard, the transient receptor potential ankyrin 1 (TRPA1) has been studied in inflammatory and painful conditions. Thus, this study aimed to evaluate the antinociceptive and anti-inflammatory effect of the topical application of a TRPA1 antagonist in a model of traumatic muscle injury in rats. The mechanical trauma model was developed by a single blunt trauma impact on the right gastrocnemius muscle of Wistar male rats (250-350 g). The animals were divided into four groups (Sham/Vehicle; Sham/HC-030031 0.05%; Injury/Vehicle, and Injury/HC-030031 0.05%) and topically treated with a Lanette® N cream base containing a TRPA1 antagonist (HC-030031, 0.05%; 200 mg/muscle) or vehicle (Lanette® N cream base; 200 mg/muscle), which was applied at 2, 6, 12, 24, and 46 h after muscle injury. Furthermore, we evaluated the contribution of the TRPA1 channel on nociceptive, inflammatory, and oxidative parameters. The topical application of TRPA1 antagonist reduced biomarkers of muscle injury (lactate/glucose ratio), spontaneous nociception (rat grimace scale), inflammatory (inflammatory cell infiltration, cytokine levels, myeloperoxidase, and N-acetyl-β-D-glucosaminidase activities) and oxidative (nitrite levels and dichlorofluorescein fluorescence) parameters, and mRNA Trpa1 levels in the muscle tissue. Thus, these results demonstrate that TRPA1 may be a promising anti-inflammatory and antinociceptive target in treating muscle pain after traumatic muscle injury.

摘要

肌肉骨骼疼痛是一个广泛存在的公共健康问题,尤其是在创伤性肌肉损伤后。此外,它也是导致残疾的常见原因,但这种疼痛仍然管理不善。然而,创伤性肌肉损伤相关疼痛和炎症的病理生理学尚未完全阐明。在这方面,瞬时受体电位锚蛋白 1(TRPA1)已在炎症和疼痛状态下进行了研究。因此,本研究旨在评估在大鼠创伤性肌肉损伤模型中局部应用 TRPA1 拮抗剂的镇痛和抗炎作用。通过对 Wistar 雄性大鼠(250-350g)右侧比目鱼肌单次钝性创伤冲击建立机械性创伤模型。动物分为 4 组(Sham/Vehicle;Sham/HC-030031 0.05%;Injury/Vehicle 和 Injury/HC-030031 0.05%),并局部用含有 TRPA1 拮抗剂(HC-030031,0.05%;200mg/肌肉)或载体(Lanette®N 乳膏基质;200mg/肌肉)的 Lanette®N 乳膏基质处理,在肌肉损伤后 2、6、12、24 和 46 小时进行治疗。此外,我们评估了 TRPA1 通道对伤害感受、炎症和氧化参数的贡献。TRPA1 拮抗剂的局部应用降低了肌肉损伤的生物标志物(乳酸/葡萄糖比)、自发性疼痛感受(大鼠痛苦表情量表)、炎症(炎性细胞浸润、细胞因子水平、髓过氧化物酶和 N-乙酰-β-D-氨基葡萄糖苷酶活性)和氧化(亚硝酸盐水平和二氯荧光素荧光)参数,以及肌肉组织中 Trpa1 mRNA 水平。因此,这些结果表明,TRPA1 可能是治疗创伤性肌肉损伤后肌肉疼痛的一种有前途的抗炎和镇痛靶点。

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[8]
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[9]
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[10]
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