Metamizole relieves pain by influencing cytokine levels in dorsal root ganglia in a rat model of neuropathic pain
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ARTICLE
Metamizole relieves pain by influencing cytokine levels in dorsal root ganglia in a rat model of neuropathic pain Renata Zajaczkowska1 · Klaudia Kwiatkowski2 · Katarzyna Pawlik2 · Anna Piotrowska2 · Ewelina Rojewska2 · Wioletta Makuch2 · Jerzy Wordliczek1 · Joanna Mika2 Received: 26 February 2020 / Revised: 9 July 2020 / Accepted: 13 July 2020 © The Author(s) 2020
Abstract Background 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. Methods 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. Results 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. Conclusions 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. Graphic abstract
7th day
von Frey test [g]
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Metamizol relieves neuropathic pain through changing the mRNA and/or protein level of important nociceptive factors
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MET
DRG
CCI
I L-1beta I L-18 I L-6 CCL2 CCL4 Vehicle-treated rats CCL7 Metamizol-treated rats
CCL1 CCL3 CCL6 CCL9 CCL17 CCL22 XCL1
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R. Zajaczkowska et al.
Keywords Interleukins · Chemokines · IL-1beta · IL-18 · IL-6 · CCL2 · CCL4 · CCL7 · Metamizole
Introduction Chronic pain occurs in approximately 20% of the general population [1], and the prevalence of neuropathic pain is 6.9% [2]. In a review [3] based on 174 published clinical trials, it was reported that there are no drug treatments available that can relieve all neuropathic pain conditions. Recently, accumulating evidence has demonstrated that neuroinflammation at the level of dorsal root gang
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