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Metamizol potentiates morphine antinociception but not constipation after chronic treatment
Gloria P Hernández-Delgadillo1, Rosa Ventura Martínez, Ma Irene Díaz Reval
1Departamento de Farmacobiología, CINVESTAV-IPN, Calz. de los Tenorios No. 235 Col. Granjas Coapa, Deleg. Tlalpan, C.P. 14330, Mexico City, Mexico.
Abstract:
This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.
Insights
This study found that combining morphine and metamizol significantly enhances pain relief and its duration in rats, even with chronic use. Metamizol did not worsen morphine-induced constipation, suggesting a beneficial combination for chronic pain management.
Area of Science:
- Pharmacology
- Pain Management
- Toxicology
Background:
- Opioid analgesics like morphine are effective for pain but can lead to tolerance and side effects.
- Non-opioid analgesics are often used in combination to improve efficacy and reduce opioid dosage.
- The interaction between morphine and metamizol on antinociception and gastrointestinal effects requires further investigation.
Purpose of the Study:
- To evaluate the antinociceptive and constipating effects of a morphine and metamizol combination in rats.
- To assess the impact of acute and chronic co-administration on pain relief and intestinal transit.
- To explore the potential for synergistic effects and tolerance development.
Main Methods:
- Rats received acute or chronic (12-day) subcutaneous administration of morphine and metamizol.
- Antinociceptive effects were measured using inflammatory nociception and pain-induced functional impairment models.
- Intestinal transit was evaluated using the charcoal meal test.
- Naloxone was used to probe the involvement of the opioidergic system.
Main Results:
- The combination markedly potentiated antinociception and prolonged its duration compared to morphine alone, in both acute and chronic treatments.
- Morphine's antinociceptive effect diminished with chronic use, but the combination's efficacy remained consistent.
- Constipating effects of morphine did not show tolerance, and metamizol did not potentiate this side effect.
- Naloxone partially reversed the combination's antinociceptive effects, indicating partial opioid system involvement.
Conclusions:
- Morphine and metamizol exhibit significant synergistic antinociceptive effects, particularly in chronic treatment models.
- The combination demonstrates sustained efficacy without potentiating morphine-induced constipation.
- This combination holds promise for managing chronic pain conditions, potentially offering improved analgesia with a manageable side effect profile.