title: Antinociceptive effect of systemically administered dipyrone (metamizol), magnesium chloride or both in a murine model of cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  DIP promoted antinociception only at the beginning of both protocols due to the development of tolerance. The combination DIP-MgCl2improved the antinociceptive effect, avoiding tolerance and reducing tumour growth in the preventive treatment, more efficiently than each compound alone.
  
  
  
  These results suggest that DIP-MgCl2may 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.
  
  
  
  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.affiliation: Laboratory of Cellular and Molecular Pathology, Center for Experimental Medicine, Venezuelan Institute for Scientific Research (IVIC), Caracas, Bolivarian Republic of Venezuela.
authors.forename: B E
authors.initials: BE
authors.lastname: Brito
authors.affiliation: Laboratory of Neurophysiology, Center for Biophysics and Biochemistry, Venezuelan Institute for Scientific Research (IVIC), Caracas, Bolivarian Republic of Venezuela.|School of Psychology, Andrés Bello Catholic University, Caracas, Bolivarian Republic of Venezuela.
authors.forename: E
authors.initials: E
authors.lastname: Vazquez
authors.affiliation: Laboratory of Cellular and Molecular Pathology, Center for Experimental Medicine, Venezuelan Institute for Scientific Research (IVIC), Caracas, Bolivarian Republic of Venezuela.
authors.forename: P
authors.initials: P
authors.lastname: Taylor
authors.affiliation: Laboratory of Molecular Characterization and Biomolecules, Department of Research Materials, Technology and Environment, Venezuelan Institute for Scientific Research (IVIC), Caracas, Bolivarian Republic of Venezuela.
authors.forename: Y
authors.initials: Y
authors.lastname: Alvarado
authors.affiliation: Laboratory of Neurophysiology, Center for Biophysics and Biochemistry, Venezuelan Institute for Scientific Research (IVIC), Caracas, Bolivarian Republic of Venezuela.
authors.forename: H
authors.initials: H
authors.lastname: Vanegas
authors.affiliation: Department of Behavioral Sciences, Metropolitan University (UNIMET), Caracas, Bolivarian Republic of Venezuela.
authors.forename: A
authors.initials: A
authors.lastname: Millan
authors.affiliation: Laboratory of Neurophysiology, Center for Biophysics and Biochemistry, Venezuelan Institute for Scientific Research (IVIC), Caracas, Bolivarian Republic of Venezuela.|School of Psychology, Andrés Bello Catholic University, Caracas, Bolivarian Republic of Venezuela.|Department of Behavioral Sciences, Metropolitan University (UNIMET), Caracas, Bolivarian Republic of Venezuela.
authors.forename: V
authors.initials: V
authors.lastname: Tortorici
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D000072716:Cancer Pain / Q000188:drug therapy* / Q000523:psychology; D004177:Dipyrone / Q000008:administration & dosage / Q000494:pharmacology*; D018450:Disease Progression; D004338:Drug Combinations; D004361:Drug Tolerance; D015636:Magnesium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010147:Pain Measurement / Q000187:drug effects
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D015636:Magnesium Chloride; D004177:Dipyrone