ADJUVANT STRATEGIES TO ENHANCE THE ANALGESIC EFFECT OF MELOXICAM: EXPERIMENTAL RATIONALE FOR MULTIMODAL ANALGESIA

Abstract

Background. Meloxicam (MEL), a predominantly selective COX-2 inhibitor, is known to reduce opioid requirements in postoperative patients; however, the choice of optimal dose and adjuvant combinations remains an unresolved clinical challenge. The combination of drugs within the framework of multimodal analgesia (MMA) aims to enhance efficacy and minimize adverse effects. Purpose – to evaluate the influence of adjuvant analgesics (gabapentin (GAB), pregabalin (PREG), amitriptyline hydrochloride (AMI), ketamine hydrochloride (KTM), and dexmedetomidine hydrochloride (DMM)) on the analgesic potency of MEL in a model of acute visceral pain. Materials and Methods. The study was conducted on 56 mature male white outbred mice randomized into 8 groups of 7 animals each. Visceral pain was modeled using the acetic acid–induced writhing test. Morphine (6.2 mg/kg) served as the reference drug. Meloxicam was administered at a dose of 1.9 mg/kg, both alone and in combination with GAB, PREG, AMI, KTM, or DMM. Results. Meloxicam monotherapy reduced the number of writhes to 36 [33; 37] (p < 0.001), corresponding to a 33.3% reduction in pain response versus control; however, its effect was 63.9% lower than that of morphine (p < 0.05). The addition of adjuvants progressively enhanced analgesia: MEL+GAB – 26 [22; 30] (p < 0.001 vs control; p = 0.02 vs MEL), MEL+PREG – 24 [22; 30] (p < 0.001 vs control; p = 0.03 vs MEL), MEL+AMI – 20 [18; 23] (p < 0.001 vs control; p = 0.03 vs MEL), MEL+KTM – 21 [17; 25] (p < 0.001 vs control; p < 0.001 vs MEL), MEL+DMM – 17 [15; 19] (p < 0.001 vs control; p < 0.001 vs MEL). The ordered sequence of medians (36 → 26 → 24 → 20 → 21 → 17) reflects a consistent hierarchy of analgesic enhancement, with the deepest and most stable reduction in pain reactions observed for combinations with dexmedetomidine and amitriptyline. Conclusions. In the acetic acid writhing test, meloxicam exhibits baseline analgesic activity, while the addition of gabapentin, pregabalin, amitriptyline, ketamine, or dexmedetomidine significantly enhances the analgesic effect. The most pronounced and stable results were observed for MEL+DMM and MEL+AMI combinations.