PnPP-15, a Synthetic Peptide Derived from a Toxin from IPhoneutria nigriventer/I Spider Venom, Alleviates Diabetic Neuropathic Pain and Acts Synergistically with Pregabalin in Mice

Diabetic neuropathic pain is one of the complications that affect a wide variety of the diabetic population and is often difficult to treat. Only a small number of patients experience pain relief, which usually comes with onerous side effects and low levels of satisfaction. The search for new analge...

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Bibliographic Details
Published in:Toxins 2023-09, Vol.15 (9)
Main Authors: Mariano, Xavier Maia, de Assis Ferreira, Luana Caroline, Almeida-Leite, Camila Megale, de Castro Junior, Célio José, de Lima, Maria Elena
Format: Article
Language:English
Subjects:
Animal experimentation
Care and treatment
Chronic pain
Complications and side effects
Composition
Development and progression
Diabetic neuropathies
Dosage and administration
Evaluation
Methods
Peptides
Pregabalin
Properties
Spider venom
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Summary:Diabetic neuropathic pain is one of the complications that affect a wide variety of the diabetic population and is often difficult to treat. Only a small number of patients experience pain relief, which usually comes with onerous side effects and low levels of satisfaction. The search for new analgesic drugs is necessary, given the limitations that current drugs present. Combining drugs to treat neuropathic pain has been attracting interest to improve their efficacy compared to single-drug monotherapies while also reducing dose sizes to minimize side effects. The aim of our study was to verify the antinociceptive effect of a synthetic peptide, PnPP-15, alone and combined with pregabalin, in male Swiss diabetic mice using the von Frey method. PnPP-15 is a synthetic peptide derived from PnPP19, a peptide representing a discontinuous epitope of the primary structure of the toxin PnTx2-6 from the venom of the spider Phoneutria nigriventer. The antinociceptive activity of both compounds was dose-dependent and showed synergism, which was verified by isobolographic analysis. Treatment with PnPP-15 did not cause spontaneous or forced motor changes and did not cause any damage or signs of toxicity in the analyzed organs (pancreas, lung, heart, kidney, brain, or liver). In conclusion, PnPP-15 is a great candidate for an analgesic drug against neuropathic pain caused by diabetes and exerts a synergistic effect when combined with pregabalin, allowing for even more efficient treatment.
ISSN:2072-6651
2072-6651
DOI:10.3390/toxins15090560