Analgesic and side effects of intravenous recombinant Phα1β

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 ED 50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (E max = 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.

Neuroprotective effect of CTK 01512‐2 recombinant toxin at the spinal cord in a model of Huntington's disease

“…As a calcium blocker, CTK 01512‐2 might be a good candidate for the preservation of some neuronal functions, such as muscle innervation. Another advantage of CTK 01512‐2 is the low toxicity seen by us and others (Rigo et al., 2020), which further supports preclinical analyses (Nicoletti et al., 2017). CTK 01512‐2 might therefore display a good safety profile.…”

Analgesic effects of Phα1β toxin: a review of mechanisms of action involving pain pathways

“…administered CTK 01512-2 were also studied in the CCL-induced neuropathic pain and paclitaxel-induced acute and chronic pain in which the recombinant toxin exerted analgesic action. The analgesic effects were not accompanied by acute toxicity compared to morphine that induced significant changes in motor activity, HR, and blood pressure [134]. The analgesic effect was also elicited in male and female mice by CTK 01512-2 (0.06 and 0.6 mg/kg i.v) in a complex regional pain syndrome 1 model; the peptide attenuated mechanical and cold allodynia in the acute and chronic nociceptive state [135].…”

Animal Venom Peptides Cause Antinociceptive Effects by Voltage-gated Calcium Channels Activity Blockage

“…Therefore, CTK 01512-2 i.v. did not induce motor alteration or alter cardiac parameters and biochemical markers in mice [ 145 ].…”