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

Abstract

BACKGROUND:

Opioid effectiveness to treat cancer pain is often compromised by the development of tolerance and the occurrence of undesirable side effects, particularly during long-term treatment. Hence, the search for more efficient analgesics remains a necessity. The main goal of this study was to relieve neuropathic symptoms associated with tumour growth by administering the non-opioid analgesic dipyrone (DIP) alone or in combination with magnesium chloride (MgCl2 ), an adjuvant that blocks the NMDA receptor channel.

METHODS:

Mice were inoculated with a melanoma cell line (B16-BL6) in the left thigh and two protocols were used to evaluate the effect of DIP (270 mg/kg), MgCl2 (200 mg/kg), or the combination DIP-MgCl2 . In the therapeutic protocol the drugs, alone or combined, were administered once tumour had promoted increased nociception. In the preventive protocol, drugs were administered prior to the appearance of the primary tumour. Tumour growth was assessed with a caliper and nociception was determined using behavioural tests.

RESULTS:

DIP promoted antinociception only at the beginning of both protocols due to the development of tolerance. The combination DIP-MgCl2 improved the antinociceptive effect, avoiding tolerance and reducing tumour growth in the preventive treatment, more efficiently than each compound alone.

CONCLUSIONS:

These results suggest that DIP-MgCl2 may represent a safe, affordable and accessible option to reduce tumour growth and to treat cancer pain avoiding the risk of tolerance, without the typical complications of opioids agents, particularly when long-term treatment is required.

SIGNIFICANCE:

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.

• Authors: B E Brito, E Vazquez, P Taylor, Y Alvarado, H Vanegas, A Millan, V Tortorici
• Journal: European journal of pain (London, England) (Eur J Pain) Vol. 21 Issue 3 Pg. 541-551 (03 2017) ISSN: 1532-2149 [Electronic] England
• PMID: 27723172 (Publication Type: Journal Article)
• Copyright: © 2016 European Pain Federation - EFIC®.

Chemical References

• Analgesics
• Anti-Inflammatory Agents, Non-Steroidal
• Drug Combinations
• Magnesium Chloride
• Dipyrone

Topics

• Analgesics (administration & dosage, pharmacology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, pharmacology)
• Behavior, Animal (drug effects)
• Cancer Pain (drug therapy, psychology)
• Dipyrone (administration & dosage, pharmacology)
• Disease Progression
• Drug Combinations
• Drug Tolerance
• Magnesium Chloride (administration & dosage, pharmacology)
• Male
• Melanoma, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Pain Measurement (drug effects)