Laboratory of Pharmacology of Pain, Department of Pharmacology, Biological Science Sector, Federal University of Paraná, Curitiba, PR, Brazil.
Laboratory of Pharmacology of Pain, Department of Pharmacology, Biological Science Sector, Federal University of Paraná, Curitiba, PR, Brazil.
Behav Brain Res. 2019 Oct 17;372:111992. doi: 10.1016/j.bbr.2019.111992. Epub 2019 May 30.
Diabetic neuropathic pain is one of the most common and debilitating complications of diabetes whose available treatments are poorly effective. Currently, omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been widely studied as a treatment of many types of pain, including inflammatory, spontaneous and neuropathic pain. However, little is known about the potential antinociceptive effect of ω-3 PUFAs (fish oil; FO or its major fatty acids, eicosapentaenoic -EPA and docosahexaenoic acids-DHA), in diabetic neuropathic pain as well as the mechanisms involved. To test, streptozotocin (STZ) -induced diabetic male Wistar rats were submitted to acute treatment with FO, EPA or DHA at the second and fourth weeks after diabetes induction (at the beginning and peak of development of mechanical allodynia, respectively). The cumulative effect of these compounds after a sub-chronic treatment for two weeks was also evaluated as well as the role of central μ-opioid receptors. It was observed that acute oral treatment with FO (0.5, 1 or 3 g/kg), EPA or DHA (100, 200 or 400 mg/kg) at the 2 or at the 4 week after STZ significantly reverted the mechanical allodynia of diabetic animals, without altering the hyperglycemia or reduced weight gain. Moreover, the sub-chronic treatment with FO, EPA or DHA induced a sustained antinociceptive effect in diabetic animals. Intriguingly, the intrathecal treatment with a μ-opioid receptor antagonist (CTOP; 10 μg/rat) completely prevented the acute effect of FO, EPA or DHA. Taken together, our data suggest that ω-3 PUFAs may represent a promising therapeutic outcome for diabetic neuropathic pain, probably acting through the opioid system activation.
糖尿病性神经病理性疼痛是糖尿病最常见和最具致残性的并发症之一，其现有治疗方法效果不佳。目前，ω-3 多不饱和脂肪酸（ω-3 PUFA）已被广泛研究用于治疗多种类型的疼痛，包括炎症性、自发性和神经性疼痛。然而，对于 ω-3 PUFA（鱼油；FO 或其主要脂肪酸，二十碳五烯酸-EPA 和二十二碳六烯酸-DHA）在糖尿病性神经病理性疼痛中的潜在镇痛作用以及涉及的机制知之甚少。为了验证这一点，链脲佐菌素（STZ）诱导的糖尿病雄性 Wistar 大鼠在糖尿病诱导后第 2 周和第 4 周（分别在机械性痛觉过敏的发展开始和高峰期）进行 FO、EPA 或 DHA 的急性治疗。还评估了这些化合物经过两周亚慢性治疗后的累积效应以及中枢 μ 阿片受体的作用。结果观察到，FO（0.5、1 或 3 g/kg）、EPA 或 DHA（100、200 或 400 mg/kg）在 STZ 后第 2 周或第 4 周的急性口服治疗显著逆转了糖尿病动物的机械性痛觉过敏，而不改变高血糖或体重减轻。此外，FO、EPA 或 DHA 的亚慢性治疗在糖尿病动物中诱导了持续的镇痛作用。有趣的是，鞘内给予 μ 阿片受体拮抗剂（CTOP；10 μg/rat）完全阻止了 FO、EPA 或 DHA 的急性作用。综上所述，我们的数据表明，ω-3 PUFA 可能代表治疗糖尿病性神经病理性疼痛的有希望的治疗结果，可能通过激活阿片系统起作用。
