1. Intravenous administration of recombinant Phα1β: Antinociceptive properties and morphine tolerance reversal in a cancer-associated pain model.
- Author
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de Melo Cardoso M, Scussel R, da Silva Abel J, Pereira FO, Cruz LA, da Costa Constante F, De Pieri E, Abelaira HM, Ferreira J, Gomez MV, Rigo FK, and Machado-de-Ávila RA
- Subjects
- Animals, Mice, Analgesics therapeutic use, Analgesics pharmacology, Analgesics, Opioid therapeutic use, Analgesics, Opioid administration & dosage, Disease Models, Animal, Hyperalgesia drug therapy, Recombinant Proteins therapeutic use, Administration, Intravenous, Cancer Pain drug therapy, Drug Tolerance, Morphine administration & dosage, Morphine therapeutic use, Morphine pharmacology, Spider Venoms pharmacology, Spider Venoms therapeutic use
- Abstract
Cancer-related pain is considered one of the most prevalent symptoms for those affected by cancer, significantly influencing quality of life and treatment outcomes. Morphine is currently employed for analgesic treatment in this case, however, chronic use of this opioid is limited by the development of analgesic tolerance and adverse effects, such as digestive and neurological disorders. Alternative therapies, such as ion channel blockade, are explored. The toxin Phα1β has demonstrated efficacy in blocking calcium channels, making it a potential candidate for alleviating cancer-related pain. This study aims to assess the antinociceptive effects resulting from intravenous administration of the recombinant form of Phα1β (r-Phα1β) in an experimental model of cancer-related pain in mice, tolerant or not to morphine. The model of cancer-induced pain was used to evaluate these effects, with the injection of B16F10 cells, followed by the administration of the r-Phα1β, and evaluation of the mechanical threshold by the von Frey test. Also, adverse effects were assessed using a score scale, the rotarod, and open field tests. Results indicate that the administration of r-Phα1β provoked antinociception in animals with cancer-induced mechanical hyperalgesia, with or without morphine tolerance. Previous administration of r-Phα1β was able to recover the analgesic activity of morphine in animals tolerant to this opioid. r-Phα1β was proved safe for these parameters, as no adverse effects related to motor and behavioral activity were observed following intravenous administration. This study suggests that the concomitant use of morphine and r-Phα1β could be a viable strategy for pain modulation in cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.) more...
- Published
- 2024
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