Department of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, Messina, Italy.
Institute of Anaesthesiology and Reanimation, Catholic University of the Sacred Heart, Rome, Italy.
FASEB J. 2019 Oct;33(10):11364-11380. doi: 10.1096/fj.201900538R. Epub 2019 Jul 25.
Diabetic peripheral neuropathy (DPN) is a complication of diabetes connected with morbidity and mortality. DPN presents deterioration of peripheral nerves with pain, feebleness, and loss of sensation. Particular medications might display their remedial potential by controlling neuroinflammation. Palmitoylethanolamide (PEA) is an autacoid local injury antagonist distinguished for its neuroprotective, analgesic, and anti-inflammatory properties in numerous experimental models of neuroinflammation. Based on these findings, the goal of this work was to better test the neuroprotective effects of a formulation of micronized PEA (PEA-m) and the probable mechanism of action in a mouse model of DPN induced by streptozotocin (STZ) injection. Diabetic and control animals received PEA-m (10 mg/kg) by oral gavage daily starting 2 wk from STZ injection. After 16 wk, the animals were euthanized, and blood, urine, spinal cord, and sciatic nerve tissues were collected. Our results demonstrated that after diabetes induction, PEA-m was able to reduce mechanical, thermal hyperalgesia, and motor alterations as well as reduce mast cell activation and nerve growth factor expression. In addition, PEA-m decreased neural histologic damage, oxidative and nitrosative stress, cytokine release, angiogenesis, and apoptosis. Moreover, spinal microglia activation (IBA-1), phospho-P38 MAPK, and nuclear factor NF-κB inflammatory pathways were also inhibited. The protective effects of PEA-m could be correlated at least in part to peroxisome proliferator-activated receptor-α activation. In summary, we demonstrated that PEA-m represents a new therapeutic strategy for neuroinflammation pain associated with mixed neuropathies.-Impellizzeri, D., Peritore, A. F., Cordaro, M., Gugliandolo, E., Siracusa, R., Crupi, R., D'Amico, R., Fusco, R., Evangelista, M., Cuzzocrea, S., Di Paola, R. The neuroprotective effects of micronized PEA (PEA-m) formulation on diabetic peripheral neuropathy in mice.
糖尿病周围神经病变（DPN）是一种与发病率和死亡率相关的糖尿病并发症。DPN 表现为外周神经恶化，伴有疼痛、无力和感觉丧失。某些药物可能通过控制神经炎症显示其治疗潜力。棕榈酸乙醇酰胺（PEA）是一种自代谢局部损伤拮抗剂，因其在多种神经炎症的实验模型中具有神经保护、镇痛和抗炎特性而闻名。基于这些发现，本工作的目的是更好地测试微粉化 PEA（PEA-m）配方的神经保护作用及其在链脲佐菌素（STZ）注射诱导的 DPN 小鼠模型中的可能作用机制。糖尿病和对照动物从 STZ 注射后 2 周开始每天通过口服灌胃接受 PEA-m（10mg/kg）。16 周后，处死动物，收集血液、尿液、脊髓和坐骨神经组织。我们的结果表明，在糖尿病诱导后，PEA-m 能够减轻机械性、热痛觉过敏和运动改变，减少肥大细胞活化和神经生长因子表达。此外，PEA-m 降低了神经组织学损伤、氧化和硝化应激、细胞因子释放、血管生成和细胞凋亡。此外，脊髓小胶质细胞激活（IBA-1）、磷酸化 P38 MAPK 和核因子 NF-κB 炎症途径也被抑制。PEA-m 的保护作用至少部分与过氧化物酶体增殖物激活受体-α激活相关。总之，我们证明了 PEA-m 代表了一种与混合神经病变相关的神经炎症疼痛的新治疗策略。
