The Effect of Anakinra on Acrylamide-induced Peripheral Neuropathy and Neuropathic Pain in Rats

Abstract Acrylamide is a neurotoxic compound. Moreover, anakinra is an interleukin-1 (IL-1) receptor antagonist used in rheumatoid arthritis treatment. This study investigated the effect of anakinra on acrylamide-related neuropathy and neuropathic pain. Acrylamide exposure caused a significant decrease in the pain threshold; an increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) levels; and a decrease in total glutathione (tGSH) values in the sciatic nerve. This indicates hyperalgesia presence, oxidative stress, and peripheral nerve tissue inflammation. Anakinra treatment significantly reduced the MDA, IL-1β, and TNF-α levels, and increased the pain threshold and mean tGSH values. The analgesic effect of anakinra was 67.9% at the first hour, increasing to 74.9% and 76.7% at the second and third hours, respectively. The group receiving acrylamide exhibited histopathological changes (e.g., swollen and degenerated axons, hypertrophic and hyperplasic Schwann cells, and congested vessels). The use of anakinra significantly improved these morphological changes. Anakinra is concluded to reduce neuropathic pain and prevent neurotoxic effect of acrylamide on peripheral nerves due to its analgesic, antioxidant, and anti-inflammatory properties.

摘要 丙烯酰胺（Acrylamide）是一种神经毒性化合物。阿那白滞素（anakinra）是一款用于类风湿关节炎（rheumatoid arthritis）治疗的白细胞介素-1（IL-1）受体拮抗剂。本研究探讨了阿那白滞素对丙烯酰胺相关神经病变（neuropathy）及神经病理性疼痛（neuropathic pain）的干预效应。丙烯酰胺暴露可显著降低痛阈（pain threshold），升高坐骨神经（sciatic nerve）中丙二醛（MDA）、肿瘤坏死因子-α（TNF-α）及白细胞介素-1β（IL-1β）水平，并降低总谷胱甘肽（tGSH）含量，提示痛觉过敏（hyperalgesia）、氧化应激（oxidative stress）及周围神经组织炎症的发生。阿那白滞素干预可显著下调MDA、IL-1β及TNF-α水平，同时提升痛阈与总谷胱甘肽均值。阿那白滞素的镇痛效果在给药后1小时达67.9%，于第2、3小时分别升至74.9%与76.7%。仅接受丙烯酰胺暴露的实验组出现组织病理学改变，包括轴突肿胀变性、施万细胞（Schwann cells）肥大增生及血管充血；阿那白滞素干预可显著改善上述形态学异常。综上，阿那白滞素凭借其镇痛、抗氧化及抗炎特性，可减轻丙烯酰胺诱导的神经病理性疼痛，并阻断丙烯酰胺对周围神经的神经毒性作用。