Analgesic Effect of Metamizole in Cold-induced Pain
The cold test is used to experimentally induce acute pain – it can thus be used, for example, to test the efficacy of analgesics. The authors of a recently published German study evaluated the analgesic effect and tolerability of metamizole compared to opioid analgesics using this method. They were led by the fact that although the drug has proven clinical efficacy and safety, it has not yet been tested using this procedure, unlike opioids.
Cold Test
The cold test (CPT – cold pressor test) is performed by immersing a limb in cold water until individual pain tolerance is reached. The test assesses the onset (i.e., threshold) of pain, its intensity, and the withdrawal time (pain tolerance).
Pooled Data Analysis and Methodology of Data Collection
Experts from the University Hospital in Essen conducted a pooled analysis of data from 264 healthy volunteers from 3 randomized placebo-controlled double-blind substudies. They compared a single dose of 800 mg metamizole with two different doses of the opioid combination tilidine/naloxone (50/4 mg and 100/8 mg) and placebo using the CPT. The intensity of pain, its tolerance, adverse events attributed to the medication, changes in blood pressure, and heart rate were evaluated. Pain intensity was assessed as the percentage of the area under the pain curve (%AUPC). Pain tolerance was defined as the withdrawal time of the hand from the water bath. The maximum immersion time was limited to 180 s.
The first CPT was performed before the administration of the analgesics. Then, 100/8 mg of tilidine/naloxone (substudy 1), 50/4 mg of tilidine/naloxone (substudy 2), 800 mg of metamizole (substudy 3), or purified water in capsules (control group in all substudy) was orally administered. A second test was conducted after 35 minutes. Participants performed continuous pain assessments on a visual analog scale (VAS) using a mechanical slider during both tests.
Results
Analgesic Effects, Safety, and Tolerability of Tilidine/Naloxone
Both doses of opioids significantly reduced %AUPC and increased pain tolerance. The higher dose was associated with a greater reduction in %AUPC and a higher increase in pain tolerance than the lower opioid dose. A significantly higher incidence of adverse events attributed to the medication was described for both doses compared to the control group. Dizziness, nausea, and vomiting were reported. Two serious adverse events requiring medical intervention occurred in the higher dose group. No changes in blood pressure and heart rate were detected.
Analgesic Effects, Safety, and Tolerability of Metamizole
Metamizole led to a significant reduction in %AUPC and an increase in pain tolerance compared to the control group. No statistically significant differences in the incidence of adverse events attributed to the medication were detected compared to placebo. No changes in blood pressure and heart rate occurred either.
Comparison of Metamizole and Opioids
A pooled analysis of data from all 3 studies showed comparable reductions in %AUPC and increased pain tolerance with metamizole and both low and high doses of opioids. The incidence of adverse events attributed to the medication was significantly lower in the metamizole group than in the opioid groups.
Conclusion
Metamizole led to a comparable reduction in acute cold-induced pain in healthy volunteers as both doses of opioid analgesics. However, it showed significantly better tolerability comparable to placebo. According to the results of this study, the combination of metamizole with CPT represents a safe, tolerable, and effective experimental model for evaluating pharmacologically induced analgesia.
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Source: Kleine‐Borgmann J., Wilhelmi J., Kratel J. et al. Tilidine and dipyrone (metamizole) in cold pressor pain: a pooled analysis of efficacy, tolerability, and safety in healthy volunteers. Clin Transl Sci 2021 Sep; 14(5): 1997–2007, doi: 10.1111/cts.13058.
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