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Analgesic and side effects of intravenous recombinant Phα1β

Flavia Karine Rigo1, Mateus Fortes Rossato2, Vanessa Borges2, Juliana Figueira da Silva3, Elizete Maria Rita Pereira3, Ricardo Andrez Machado de Ávila1, Gabriela Trevisan1, Duana Carvalho dos Santos3, Danuza Montijo Diniz3, Marco Aurélio Romano Silva4, Célio José de Castro Junior3, Thiago Mattar Cunha2, Juliano Ferreira5, Marcus Vinicius Gomez3
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J Venom Anim Toxins incl Trop Dis, 2020, 26: e20190070
Received: 18 September 2019 | Accepted: 18 February 2020 | Published online: 17 April 2020
http://dx.doi.org/10.1590/1678-9199-JVATITD-2019-0070

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.

 

Keywords: Recombinant Phα1β; Analgesia; Neuropathic pain; Intravenous drug delivery system; Side effects, Cardiac function, Motor activity, Biochemicals

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