Institute of Health Sciences, Department of Pharmacology, Anadolu University, 26470, Eskisehir, Turkey.
Faculty of Pharmacy, Department of Pharmacology, Anadolu University, 26470, Eskisehir, Turkey.
Daru. 2019 Dec;27(2):605-612. doi: 10.1007/s40199-019-00288-x. Epub 2019 Jul 19.
Protocatechuic acid is an antioxidant which is shown to have analgesic activity in limited studies. However, the mechanisms of action remain unclear.
It is aimed to investigate the possible contribution of cannabinoid system that supresses the nociceptive process by the activation of CB1 and CB2 receptors in central and peripheral levels of pain pathways, to the analgesic activity of protocatechuic acid.
The analgesic activity of protocatechuic acid was determined at the doses of 75, 150 and 300 mg/kg (i.p.) by acetic acid-induced writhing and tail-immersion tests in mice. The results were compared to the analgesic effect of 300 mg/kg (i.p.) dipyrone and non-specific CB receptor agonist 5 mg/kg (i.p.) WIN 55,212-2. For investigating the contribution of cannabinoid system to protocatechuic acid analgesia; pre-treatment with 8 mg/kg (i.p.) CB1 antagonist AM251 and 8 mg/kg (i.p.) CB2 antagonist AM630 were performed separately before 300 mg/kg protocatechuic acid administration.
It was determined that protocatechuic acid has dose-dependent analgesic effect independently from locomotor activity and is comparable with effects of dipyrone and WIN 55,212-2. Pre-treatment with CB1 receptor antagonist AM251 significantly antagonized the protocatechuic acid-induced analgesia in the tail-immersion and writhing tests, whereas pre-treatment of CB2 receptor antagonist AM630 was found to be effective only in the tail-immersion test.
It is concluded that cannabinoid modulation contributes to the analgesic effect of protocatechuic acid in spinal level rather than peripheral. CB1 receptor stimulation rather than CB2 receptor stimulation mediates the analgesic effect of protocatechuic acid in both levels, especially peripheral. Graphical abstract Protocatechuic acid inhibits pain response via cannabinoidergic system.
原儿茶酸是一种抗氧化剂，有限的研究表明其具有镇痛活性。然而，其作用机制尚不清楚。
本研究旨在探讨大麻素系统通过激活中枢和外周疼痛通路中的 CB1 和 CB2 受体对疼痛过程的抑制作用，是否有助于原儿茶酸的镇痛活性。
采用醋酸诱导的扭体和尾部浸入试验，在小鼠中分别以 75、150 和 300mg/kg（ip）剂量测定原儿茶酸的镇痛活性。将结果与 300mg/kg（ip）双氯芬酸和非特异性 CB 受体激动剂 5mg/kg（ip）WIN 55,212-2 的镇痛作用进行比较。为了研究大麻素系统对原儿茶酸镇痛作用的贡献，在给予 300mg/kg 原儿茶酸之前，分别预先给予 8mg/kg（ip）CB1 拮抗剂 AM251 和 8mg/kg（ip）CB2 拮抗剂 AM630。
结果表明，原儿茶酸具有剂量依赖性的镇痛作用，与双氯芬酸和 WIN 55,212-2 的作用相当。CB1 受体拮抗剂 AM251 的预处理显著拮抗了尾部浸入试验和扭体试验中原儿茶酸引起的镇痛作用，而 CB2 受体拮抗剂 AM630 的预处理仅在尾部浸入试验中有效。
结论是，大麻素调节有助于原儿茶酸在脊髓水平而非外周水平发挥镇痛作用。CB1 受体的刺激而非 CB2 受体的刺激介导了原儿茶酸在这两个水平的镇痛作用，特别是在外周水平。
原儿茶酸通过大麻素能系统抑制疼痛反应。
