Antinociceptive effect of systemically administered dipyrone (metamizol), magnesium chloride or both in a murine model of cancer

Brito, B.E.; Vázquez, Enrique; Taylor, Peter; Alvarado, Ysaías J.; Vanegas, Horacio; Millán, Anthony; Tortorici, Vı́ctor

doi:10.1002/ejp.957

Cited by 10 publications

(13 citation statements)

References 53 publications

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“…They also reported that at higher doses, metamizole was as effective as morphine 60 mg/day [58,60]. Metamizole in combination with magnesium chloride was shown to reduce cancer pain while also preventing tolerance in a study conducted with murine model of cancer [61]. Hearn and colleagues detailed in their systematic review, from eight studies, 70% of the adult patients with acute postoperative pain who were treated with a single dose of metamizole experienced at least 50% of maximum pain relief over 4–6 h [59].…”

Section: Pain Medication Opioid Analgesics and Non-steroidal Antimentioning

confidence: 99%

Molecular Basis of Cancer Pain Management: An Updated Review

2019

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Pain can have a significantly negative impact on the quality of life of patients. Therefore, patients may resort to analgesics to relieve the pain. The struggle to manage pain in cancer patients effectively and safely has long been an issue in medicine. Analgesics are the mainstay treatment for pain management as they act through various methods on the peripheral and central pain pathways. However, the variability in the patient genotypes may influence a drug response and adverse drug effects that follow through. This review summarizes the observed effects of analgesics on UDP-glucuronosyl (UGT) 2B7 isoenzyme, cytochrome P450 (CYP) 2D6, μ-opioid receptor μ 1 (OPRM1), efflux transporter P-glycoprotein (P-gp) and ATP-binding cassette B1 ABCB1/multiple drug resistance 1 (MDR1) polymorphisms on the mechanism of action of these drugs in managing pain in cancer. Furthermore, this review article also discusses the responses and adverse effects caused by analgesic drugs in cancer pain management, due to the inter-individual variability in their genomes.

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Section: Pain Medication Opioid Analgesics and Non-steroidal Antimentioning

confidence: 99%

Molecular Basis of Cancer Pain Management: An Updated Review

2019

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“…33 and combined with medetomidine + midazolam by Kawai et al. 34 As shown in other species 35,36 and in mice, 37,38 metamizole is a potent analgesic and can reduce the required dose of other anaesthetics when administered in combination. The doses of butorphanol and metamizole were chosen in accordance with Erhardt et al.…”

Section: Discussionmentioning

confidence: 98%

“…Depending on the painful stimulus of the experiment, more potent analgesics could be necessary. Butorphanol, an opiate agonist-antagonist, 7 was recommended for use combined with dexmedetomidine þ tiletamine þ zolazepam in mice by Cagle et al 33 and combined with medetomidine þ midazolam by Kawai et al 34 As shown in other species 35,36 and in mice, 37,38 metamizole is a potent analgesic and can reduce the required dose of other anaesthetics when administered in combination. The doses of butorphanol and metamizole were chosen in accordance with Erhardt et al 7 With the exception of the SKM þ metamizole group, the PWR was lost in all groups with additional administration of analgesia.…”

Section: Discussionmentioning

confidence: 99%

Comparison of pre-emptive butorphanol or metamizole with ketamine +medetomidine and s-ketamine + medetomidine anaesthesia in improving intraoperative analgesia in mice

et al. 2018

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In accordance with the ‘refinement’ component of the 3Rs, the primary aim of this study was to investigate and compare ketamine + medetomidine (KM) and s-ketamine + medetomidine (SKM) anaesthetic protocols in C57BL/6J mice (both sexes). We sought to determine whether s-ketamine could provide adequate surgical tolerance at a 50% dose relative to that of ketamine racemate and whether antagonism of medetomidine could be initiated 15 min earlier. The second aim was to investigate the potential improvement in analgesia for both anaesthetic protocols by adding butorphanol or metamizole. Analgesia was tested via the pedal withdrawal reaction (PWR) to a painful stimulus. During anaesthesia, respiratory frequency, pulse oximetry, body temperature and PWR were monitored. Among the 16 mice in each group, the PWR was lost in all the KM + metamizole (35:56 ± 6:07 min), KM + butorphanol (43:45 ± 2:14 min) and SKM + butorphanol (24:03 ± 5:50 min) mice, 15 of the non-premedicated KM (37:00 ± 8:11 min) mice, and 9 of the pure SKM (20:00 ± 4:19 min) mice; the latter group increased to 11 mice (17:16 ± 5:10 min) with premedication of metamizole. In contrast to the racemic combination, s-ketamine at the dose used here did not lead to sufficient loss of the PWR. However, earlier partial antagonism of SKM resulted in a slightly shorter and qualitatively better recovery than later partial antagonism of SKM. The addition of metamizole or butorphanol to KM or SKM anaesthesia positively influences the analgesic quality. However, when butorphanol is added, controlled ventilation may be necessary, especially for male mice.

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“…Our behavioral results are in agreement with research by Nassini et al [ 31 ] and Ince et al [ 28 ], who found that metamizole not only prevents pain induced by scalpel incision in the rat paw but also diminishes tactile hypersensitivity in inflammatory (formalin, carrageenan) and neuropathic (partial sciatic nerve ligation) pain models. Moreover, it has already been shown that metamizole reduces hypersensitivity in neuropathy induced by diabetes [ 32 ] and cancer [ 33 ]. Here, for the first time, we showed that metamizole influences several immunological pronociceptive factors in DRG.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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

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Antinociceptive effect of systemically administered dipyrone (metamizol), magnesium chloride or both in a murine model of cancer

Abstract: This study shows a non-opioid analgesic combined with an adjuvant as a therapeutic option to treat cancer pain. The avoidance of antinociceptive tolerance when repeated administration is required, as well as tumor growth reduction, are additional advantages to be considered.

Cited by 10 publications

References 53 publications

Molecular Basis of Cancer Pain Management: An Updated Review

Molecular Basis of Cancer Pain Management: An Updated Review

Comparison of pre-emptive butorphanol or metamizole with ketamine +medetomidine and s-ketamine + medetomidine anaesthesia in improving intraoperative analgesia in mice

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

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