Metamizole relieves pain by influencing cytokine levels in dorsal root ganglia in a rat model of neuropathic pain

Renata Zajaczkowska,Ewelina Rojewska,Wioletta Makuch,Klaudia Kwiatkowski,Anna Piotrowska,Joanna Mika,Katarzyna Pawlik,Jerzy Wordliczek

doi:10.1007/s43440-020-00137-8

Abstract

BackgroundTreatment 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.MethodsChronic 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.ResultsOur 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.ConclusionsFinally, 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.Graphic abstract

Highlights

Chronic pain occurs in approximately 20% of the general population [1], and the prevalence of neuropathic pain is 6.9% [2]
The purpose of the research was to demonstrate for the first time using RT-qPCR and/or Western blot analysis how metamizole administration influences the levels of important pronociceptive interleukins (IL-1beta, IL-6, and IL-18) and chemokines (CCL1, CCL2, CCL3, CCL4, CCL6, CCL7, CCL9, CCL17, and CCL22) in dorsal root ganglia (DRG) 7 days after constriction injury (CCI)
We have shown that CCL17 and CCL22 mRNA are upregulated in DRG after sciatic nerve injury; the levels of these mRNAs remained unchanged after metamizole administration

Summary

Introduction

Chronic pain occurs in approximately 20% of the general population [1], and the prevalence of neuropathic pain is 6.9% [2]. Nerve injury activates nociceptive pathways and changes gene expression in DRG neurons, which may contribute to the development and maintenance of neuropathic pain. Results Our behavioral results provide evidence that repeated intraperitoneal administration of metamizole diminishes the development of neuropathic pain symptoms in rats. 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. Our results suggest that metamizole is likely to be an effective medication for neuropathic pain

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