Zajaczkowska Renata, Kwiatkowski Klaudia, Pawlik Katarzyna, Piotrowska Anna, Rojewska Ewelina, Makuch Wioletta, Wordliczek Jerzy, Mika Joanna
Department of Interdisciplinary Intensive Care, Jagiellonian University Medical College, Kraków, Poland.
Department of Pain Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Str., 31-343, Kraków, Poland.
Pharmacol Rep. 2020 Oct;72(5):1310-1322. doi: 10.1007/s43440-020-00137-8. Epub 2020 Jul 20.
Treatment of neuropathic pain is still challenging. Recent studies have suggested that dorsal root ganglia (DRG), which carry sensory neural signals from the peripheral nervous system to the central nervous system, are important for pathological nociception. A proper understanding of the significance and function of DRG and their role in pharmacotherapy can help to improve the treatment of neuropathic pain. Metamizole, also known as sulpyrine or dipyrone, is a non-opioid analgesic commonly used in clinical practice, but it is not used for neuropathic pain treatment.
Chronic constriction injury (CCI) of the sciatic nerve was induced in Wistar rats. Metamizole was administered intraperitoneally (ip) preemptively at 16 and 1 h before CCI and then twice a day for 7 days. To evaluate tactile and thermal hypersensitivity, von Frey and cold plate tests were conducted, respectively.
Our behavioral results provide evidence that repeated intraperitoneal administration of metamizole diminishes the development of neuropathic pain symptoms in rats. Simultaneously, our findings provide evidence that metamizole diminishes the expression of pronociceptive interleukins (IL-1beta, IL-6, and IL-18) and chemokines (CCL2, CCL4, and CCL7) in DRG measured 7 days after sciatic nerve injury. These assays indicate, for the first time, that metamizole exerts antinociceptive effects on nerve injury-induced neuropathic pain at the DRG level.
Finally, we indicate that metamizole-induced analgesia in neuropathy is associated with silencing of a broad spectrum of cytokines in DRG. Our results also suggest that metamizole is likely to be an effective medication for neuropathic pain.
神经性疼痛的治疗仍然具有挑战性。最近的研究表明，背根神经节（DRG）将感觉神经信号从外周神经系统传递到中枢神经系统，对病理性伤害感受至关重要。正确理解DRG的意义和功能及其在药物治疗中的作用有助于改善神经性疼痛的治疗。安乃近，也称为安痛定或双氯芬酸钠，是临床实践中常用的非阿片类镇痛药，但不用于治疗神经性疼痛。
在Wistar大鼠中诱导坐骨神经慢性压迫损伤（CCI）。在CCI前16小时和1小时腹腔内（ip）预先给予安乃近，然后每天两次，持续7天。为了评估触觉和热超敏反应，分别进行了von Frey和冷板试验。
我们的行为结果提供了证据，表明重复腹腔注射安乃近可减少大鼠神经性疼痛症状的发展。同时，我们的研究结果提供了证据，表明安乃近可减少坐骨神经损伤7天后DRG中促痛白细胞介素（IL-1β、IL-6和IL-18）和趋化因子（CCL2、CCL4和CCL7）的表达。这些测定首次表明，安乃近在DRG水平对神经损伤诱导的神经性疼痛发挥抗伤害感受作用。
最后，我们指出安乃近在神经病变中诱导的镇痛作用与DRG中广泛的细胞因子沉默有关。我们的结果还表明，安乃近可能是治疗神经性疼痛的有效药物。
