Antinociceptive synergism upon the joint use of methadone and Phα1β in a model of cancer-related pain in C57BL/6J mice

Ferreira, Luana Assis; Aoki, Caio Tavares; Santos, Duana Carvalho; Rezende, Marcio Junior; Mendes, Mariana Peluci; Moura, Rodrigo A; Delgado, Marina Ayres; Ferreira, Juliano; Gomez, Marcus V.; Castro, Célio José de

doi:10.1016/j.lfs.2021.119582

Cited by 5 publications

(2 citation statements)

References 34 publications

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“…Least squares linear regression analysis of the log dose–response curves for PnPP-15 and PGB supplied the calculation of the dose that produced 50% of antinociception [ 37 , 38 ]. PnPP-15 and PGB dose pairs were derived from the ED 50 values of the individual drugs.…”

Section: Methodsmentioning

confidence: 99%

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

Mariano,

de Assis Ferreira,

Almeida-Leite

et al. 2023

Toxins

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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.

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Section: Methodsmentioning

confidence: 99%

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

Mariano,

de Assis Ferreira,

Almeida-Leite

et al. 2023

Toxins

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“…To block the VGCCs, the channelactivating current must be disrupted, whereby the blockers and the toxins normally act by modulating the G-protein-coupled receptors [18,19,17]. CTK 01512-2 toxin has proved to have a therapeutically potential in preclinical studies of pain models, such as in ammatory [20][21][22][23][24], neuropathic [13,25,24], energy metabolism and cell death [26], cancer [27][28][29], multiple sclerosis [12], and bromyalgia [30,31]. Based on previous ndings, herein, we have investigated whether CTK 01512-2 central and systemic treatments can produce analgesic and anti-in ammatory effects in both CPIP and neuropathy induced by paclitaxel models in order to provide further evidence on its related pain mechanisms.…”

Section: Introductionmentioning

confidence: 99%

The Antihyperalgesic Effects of the Calcium Channel Blocker CTK 01512-2 Toxin in Persistent Pain Models

Cavalli

Gonçalves

Bobermin

et al. 2021

Preprint

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The CTK 01512-2 toxin is a recombinant peptide of the Phα1β version derived from the venom of the Phoneutria nigriventer spider. It is an N-type voltage-gated calcium channel (VGCC) blocker showing a prolonged effect on the prevention and reduction of nociception. Herein, CTK 01512-2 toxin was tested in two models of persistent pain, the chronic post-ischemia pain (CPIP) and the peripheral neuropathy induced by paclitaxel, to evaluate its intrathecal, systemic, and intracerebroventricular effects on mechanical hypersensitivity and thermal allodynia. The astroglial cell viability using the MTT test was also investigated. The results showed that CTK 01512-2 intrathecal and systemic treatments reduced mechanical hypersensitivity induced by CPIP, mainly between 1 – 4 h after CTK 01512-2 administration. When the CTK 01512-2 intrathecal treatment was applied, it also reduced the thermal allodynia induced by CPIP. CTK 01512-2 intracerebroventricular treatment also showed mechanical antihyperalgesic and thermal antiallodynic effects in the peripheral neuropathy induced by paclitaxel, reinforcing CTK 01512-2 therapeutically potential to treat persistent pain conditions. CTK 01512-2 further altered the astroglial cell viability in the MTT reduction assay, which may indicate its effects on the mitochondrial activity of these cells, possibly as a compensatory mechanism on calcium signaling. The current study shows CTK 01512-2 antihyperalgesic effects in persistent pain models, helping to pave new perspectives of pain relief treatments to patients affected by peripheral neuropathy and chronic pain conditions.

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Phα1β is a Promising Neuroprotective Peptide from the Phoneutria nigriventer ‘Armed’ Spider

Antunes

Caminski

Gomez

et al. 2022

Int J Pept Res Ther

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Antinociceptive synergism upon the joint use of methadone and Phα1β in a model of cancer-related pain in C57BL/6J mice

Cited by 5 publications

References 34 publications

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

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

The Antihyperalgesic Effects of the Calcium Channel Blocker CTK 01512-2 Toxin in Persistent Pain Models

Phα1β is a Promising Neuroprotective Peptide from the Phoneutria nigriventer ‘Armed’ Spider

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