Intrathecal injection of voltage-sensitive
calcium channel blocker peptide toxins exerts
analgesic effect in several
animal models of
pain . Upon intrathecal
administration , recombinant
Ph α1ß 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
Ph α1ß 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
Ph α1ß 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
Ph α1ß 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
Ph α1ß may be feasible for
drug -induced
analgesia , without causing any severe side effects.(AU)