Keywords
multimodal
pain
visceral
metamizole
ketamine
dexmedetomidine
analgesics
non-narcotic
How to Cite
Abstract
Introduction. Multimodal analgesia is a cornerstone of opioid-sparing strategies for acute pain management. Metamizole is a widely used non-opioid analgesic with combined peripheral and central mechanisms; however, its potentiation by central adjuvants requires further experimental validation.
Aim. To evaluate and compare the analgesic efficacy of metamizole administered alone and in combination with central adjuvants (gabapentin, pregabalin, ketamine, amitriptyline, dexmedetomidine) in mice, and to identify regimens providing the greatest enhancement relative to monotherapy and an opioid reference.
Materials and methods. Male mice (n=91) were randomized into 13 groups (7 animals each). Acute visceral pain was modeled using the acetic acid–induced writhing test. Antinociceptive activity was quantified by counting pain-related behaviors. Results were compared with intact controls, an opioid control, and monotherapy regimens.
Results. Metamizole sodium (MM-Na) monotherapy significantly reduced writhing to 28 [22;33], corresponding to a 48.1% decrease versus control (p < 0.001). Addition of central adjuvants produced heterogeneous effects. Combinations with gabapentin, pregabalin, or amitriptyline reduced writhes to 22 [19;32], 20 [18;22], and 20 [18;23], corresponding to 59.3–63.0% inhibition; however, superiority over MM-Na alone did not consistently reach statistical significance (p = 0.22–0.08). In contrast, MM-Na plus ketamine significantly potentiated analgesia, decreasing writhes to 17 [15;21] (–68.5% vs control; –39.3% vs MM-Na, p=0.01). The most pronounced effect was observed with MM-Na plus dexmedetomidine (13 [12;18] writhes; –75.9%), statistically comparable to morphine (p = 0.45) and significantly superior to MM-Na monotherapy (p = 0.01), indicating near-opioid-level analgesia within a non-opioid multimodal approach.
Conclusions. Metamizole is a rational basic component of multimodal analgesia. Dexmedetomidine and ketamine demonstrated the greatest potential for enhancing its analgesic effect in this experimental model.
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