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Title: Analgesic and side effects of intravenous recombinant Phα1β.
Authors: Rigo, Flavia Karine
Rossato, Mateus Fortes
Borges, Vanessa
Silva, Juliana Figueira da
Pereira, Elizete Maria Rita
Ávila, Ricardo Andrez Machado de
Trevisan, Gabriela
Astoni, Duana Carvalho dos Santos
Diniz, Danuza Montijo
Silva, Marco Aurélio Romano
Castro Junior, Célio José de
Cunha, Thiago Mattar
Ferreira, Juliano
Gomez, Marcus Vinicius
Keywords: Analgesia
Neuropathic pain
Intravenous drug delivery system
Cardiac function
Motor activity
Issue Date: 2020
Citation: RIGO, F. K. et al. Analgesic and side effects of intravenous recombinant Phα1β. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, 2020. Disponível em: <>. Acesso em: 11 out. 2022.
Abstract: Background: Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1β exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1β in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1β using Escherichia coli expression. In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic pain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1β toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1β may be feasible for drug-induced analgesia, without causing any severe side effects.
ISSN: 1678-9199
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