Analgesic and side effects of intravenous recombinant Phα1β.
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.
['Rigo|Flavia Karine|FK|', 'Rossato|Mateus Fortes|MF|', 'Borges|Vanessa|V|', 'da Silva|Juliana Figueira|JF|', 'Pereira|Elizete Maria Rita|EMR|', 'de Ávila|Ricardo Andrez Machado|RAM|', 'Trevisan|Gabriela|G|', 'Dos Santos|Duana Carvalho|DC|', 'Diniz|Danuza Montijo|DM|', 'Silva|Marco Aurélio Romano|MAR|0000-0002-6558-4639', 'de Castro|Célio José|CJ|', 'Cunha|Thiago Mattar|TM|', 'Ferreira|Juliano|J|', 'Gomez|Marcus Vinicius|MV|0000-0002-6082-930X']
Recombinant Phα1β Neuropathic pain Analgesia Intravenous drug delivery system Side effects, Cardiac function, Motor activity, Biochemicals