Synergism between metformin and analgesics/vitamin B12 in a model of painful diabetic neuropathy
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Metformin (a widely used antidiabetic drug) has demonstrated efficacy in models of painful diabetic neuropathy
(PDN), as well as certain clinical efficacy in relieving/preventing PDN. This study aimed to determine the type of
interaction between metformin and duloxetine/oxycodone/eslicarbazepine acetate [ESL]/vitamin B12 in
relieving diabetic pain hypersensitivity. Antihyperalgesic efficacy was determined using a Von Frey apparatus in
mice with streptozotocin-induced PDN. We examined metformin’s efficacy following oral (acute and prolonged
7-day treatment) and local (spinal and peripheral) application. The examined analgesics were administered in a
single oral dose, whereas vitamin B12 was intraperitoneally administered for 7 days. In combination experiments,
metformin (prolonged treatment) and analgesics/vitamin B12 were co-administered in fixed-dose fractions of
their ED50 values and the type of interaction was determined using isobolographic analysis. Metformin produced
dos...e-dependent antihyperalgesic effects in diabetic mice after oral (acute and prolonged 7-day treatment) and
local spinal/peripheral application. Two-drug metformin combinations with analgesics/vitamin B12 also dose-
dependently reduced mechanical hyperalgesia. The isobolographic analysis revealed that metformin synergises
with analgesics/vitamin B12, with a 6–7 fold dose reduction of both drugs in the examined combinations. In
conclusion, metformin reduces hyperalgesia in diabetic animals, most likely by acting at the spinal and pe-
ripheral level. Additionally, it synergizes with duloxetine/oxycodone/ESL/vitamin B12 in reducing hyperalgesia.
Metformin co-treatment may increase analgesic efficacy and enable the use of lower (and potentially safer)
analgesic doses for treating PDN. Combined metformin-vitamin B12 use may provide more effective pain relief
and mitigate metformin-induced vitamin B12 deficiency.
Кључне речи:
Painful diabetic neuropathy / Metformin / Alternative analgesics / Vitamin B12 / Isobolographic analysisИзвор:
Biomedicine and Pharmacotherapy, 2022, 153Издавач:
- Elsevier Masson s.r.l.
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
DOI: 10.1016/j.biopha.2022.113441
ISSN: 0753-3322
WoS: 000869218700001
Scopus: 2-s2.0-85135810975
Институција/група
PharmacyTY - JOUR AU - Pecikoza, Uroš AU - Tomić, Maja AU - Nastić, Katarina AU - Micov, Ana AU - Stepanović-Petrović, Radica PY - 2022 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4253 AB - Metformin (a widely used antidiabetic drug) has demonstrated efficacy in models of painful diabetic neuropathy (PDN), as well as certain clinical efficacy in relieving/preventing PDN. This study aimed to determine the type of interaction between metformin and duloxetine/oxycodone/eslicarbazepine acetate [ESL]/vitamin B12 in relieving diabetic pain hypersensitivity. Antihyperalgesic efficacy was determined using a Von Frey apparatus in mice with streptozotocin-induced PDN. We examined metformin’s efficacy following oral (acute and prolonged 7-day treatment) and local (spinal and peripheral) application. The examined analgesics were administered in a single oral dose, whereas vitamin B12 was intraperitoneally administered for 7 days. In combination experiments, metformin (prolonged treatment) and analgesics/vitamin B12 were co-administered in fixed-dose fractions of their ED50 values and the type of interaction was determined using isobolographic analysis. Metformin produced dose-dependent antihyperalgesic effects in diabetic mice after oral (acute and prolonged 7-day treatment) and local spinal/peripheral application. Two-drug metformin combinations with analgesics/vitamin B12 also dose- dependently reduced mechanical hyperalgesia. The isobolographic analysis revealed that metformin synergises with analgesics/vitamin B12, with a 6–7 fold dose reduction of both drugs in the examined combinations. In conclusion, metformin reduces hyperalgesia in diabetic animals, most likely by acting at the spinal and pe- ripheral level. Additionally, it synergizes with duloxetine/oxycodone/ESL/vitamin B12 in reducing hyperalgesia. Metformin co-treatment may increase analgesic efficacy and enable the use of lower (and potentially safer) analgesic doses for treating PDN. Combined metformin-vitamin B12 use may provide more effective pain relief and mitigate metformin-induced vitamin B12 deficiency. PB - Elsevier Masson s.r.l. T2 - Biomedicine and Pharmacotherapy T1 - Synergism between metformin and analgesics/vitamin B12 in a model of painful diabetic neuropathy VL - 153 DO - 10.1016/j.biopha.2022.113441 ER -
@article{ author = "Pecikoza, Uroš and Tomić, Maja and Nastić, Katarina and Micov, Ana and Stepanović-Petrović, Radica", year = "2022", abstract = "Metformin (a widely used antidiabetic drug) has demonstrated efficacy in models of painful diabetic neuropathy (PDN), as well as certain clinical efficacy in relieving/preventing PDN. This study aimed to determine the type of interaction between metformin and duloxetine/oxycodone/eslicarbazepine acetate [ESL]/vitamin B12 in relieving diabetic pain hypersensitivity. Antihyperalgesic efficacy was determined using a Von Frey apparatus in mice with streptozotocin-induced PDN. We examined metformin’s efficacy following oral (acute and prolonged 7-day treatment) and local (spinal and peripheral) application. The examined analgesics were administered in a single oral dose, whereas vitamin B12 was intraperitoneally administered for 7 days. In combination experiments, metformin (prolonged treatment) and analgesics/vitamin B12 were co-administered in fixed-dose fractions of their ED50 values and the type of interaction was determined using isobolographic analysis. Metformin produced dose-dependent antihyperalgesic effects in diabetic mice after oral (acute and prolonged 7-day treatment) and local spinal/peripheral application. Two-drug metformin combinations with analgesics/vitamin B12 also dose- dependently reduced mechanical hyperalgesia. The isobolographic analysis revealed that metformin synergises with analgesics/vitamin B12, with a 6–7 fold dose reduction of both drugs in the examined combinations. In conclusion, metformin reduces hyperalgesia in diabetic animals, most likely by acting at the spinal and pe- ripheral level. Additionally, it synergizes with duloxetine/oxycodone/ESL/vitamin B12 in reducing hyperalgesia. Metformin co-treatment may increase analgesic efficacy and enable the use of lower (and potentially safer) analgesic doses for treating PDN. Combined metformin-vitamin B12 use may provide more effective pain relief and mitigate metformin-induced vitamin B12 deficiency.", publisher = "Elsevier Masson s.r.l.", journal = "Biomedicine and Pharmacotherapy", title = "Synergism between metformin and analgesics/vitamin B12 in a model of painful diabetic neuropathy", volume = "153", doi = "10.1016/j.biopha.2022.113441" }
Pecikoza, U., Tomić, M., Nastić, K., Micov, A.,& Stepanović-Petrović, R.. (2022). Synergism between metformin and analgesics/vitamin B12 in a model of painful diabetic neuropathy. in Biomedicine and Pharmacotherapy Elsevier Masson s.r.l.., 153. https://doi.org/10.1016/j.biopha.2022.113441
Pecikoza U, Tomić M, Nastić K, Micov A, Stepanović-Petrović R. Synergism between metformin and analgesics/vitamin B12 in a model of painful diabetic neuropathy. in Biomedicine and Pharmacotherapy. 2022;153. doi:10.1016/j.biopha.2022.113441 .
Pecikoza, Uroš, Tomić, Maja, Nastić, Katarina, Micov, Ana, Stepanović-Petrović, Radica, "Synergism between metformin and analgesics/vitamin B12 in a model of painful diabetic neuropathy" in Biomedicine and Pharmacotherapy, 153 (2022), https://doi.org/10.1016/j.biopha.2022.113441 . .