The influence of magnesium ions on the electrophysiological, analgesic, and BDNF-induced neuromodulation of morphine effects in diabetic rats.

Authors

Przemysław Kurowski, Kamila Kulik, Agnieszka Kowalczyk, Natalia Wróblewska, Jana Kondrat, Filip Świątkowski, Magdalena Bujalska-Zadrożny

Published in

Frontiers in pharmacology. Volume 17. Pages 1855220. Epub Jul 01, 2026.

Abstract

Neuropathic pain is difficult to treat due to the involvement of multiple signaling pathways, including increased expression of sodium channels, decreased expression of potassium channels, heightened neuronal excitability from the activation of N-methyl-D-aspartate receptors (NMDARs), nerve damage leading to changes in neurotrophic factor levels, and reduced opioid efficacy. As a result, the treatment of neuropathic pain often requires a multifaceted approach. It has been shown that magnesium ions (Mg²⁺), which act as physiological antagonists of NMDARs, can augment opioid analgesia in chronic pain. The aim of this study was to assess the influence of Mg²⁺ on the electrophysiological, analgesic, and brain-derived neurotrophic factor (BDNF)-induced neuromodulation of the morphine profile in diabetic rats. Diabetes in male Wistar rats was induced by a single intramuscular injection of streptozotocin (STZ). The Plantar Test was used to assess the effect of Mg²⁺ and morphine co-treatment on STZ-induced hyperalgesia, expressed as increased warm sensitivity of the experimental rat hind paw. Ex vivo whole-cell recordings from ventrolateral periaqueductal gray (vlPAG) neurons were conducted to evaluate the frequency of action potentials evoked by incremental depolarizing current steps (current-clamp, 1-s steps). To assess glutamatergic signaling, neurons were voltage-clamped to measure NBQX-sensitive current at -70 mV and NMDA-evoked currents during depolarization in the presence of NMDA/glycine. Changes in BDNF concentrations in PAG structures were measured using an enzyme-linked immunosorbent assay. The results of our study suggest that although magnesium sulfate shows limited analgesic properties when administered alone, it can significantly enhance opioid efficacy when used as an adjunct. Moreover, the co-administration of morphine with magnesium sulfate resulted in a greater reduction in NMDA-evoked currents in diabetic rats compared to either agent alone. Overall, our findings support the concurrent use of Mg²⁺ and morphine in the treatment of neuropathic pain as a mechanism-informed adjunct strategy.

PMID:
42460019
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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