THE INFLUENCE OF MAGNESIUM IONS ON THE ELECTROPHYSIOLOGICAL, ANALGESIC, AND BDNF-INDUCED NEUROMODULATION OF MORPHINE EFFECTS IN DIABETIC RATS

Neuropathic pain is difficult to treat because it involves multiple mechanisms, including altered ion channel activity, increased NMDAR-mediated excitability, changes in neurotrophic factors, and reduced opioid efficacy. Therefore, effective therapy often requires a multifaceted approach. Magnesium ions (Mg²⁺), as natural NMDAR antagonists, have been shown to enhance opioid analgesia. This study investigated the effects of Mg²⁺ on the analgesic, electrophysiological, and BDNF-related modulation of morphine in diabetic rats.

Diabetes was induced in male Wistar rats using streptozotocin. Thermal hyperalgesia was assessed with the Plantar Test. Electrophysiological recordings from ventrolateral periaqueductal gray (vlPAG) neurons evaluated neuronal excitability and NMDA- and AMPA-mediated currents. BDNF levels in PAG structures were measured using enzyme-linked immunosorbent assays.

Magnesium sulfate alone showed limited analgesic effects. However, in combination with morphine, it significantly enhanced pain relief. Co-treatment reduced NMDA-evoked currents and attenuated diabetes-induced hyperexcitability in vlPAG neurons more effectively than either agent alone. Additionally, the combined therapy positively influenced BDNF-related neuromodulation. These findings indicate that magnesium sulfate can potentiate morphine analgesia by modulating glutamatergic signaling and neurotrophic pathways. The study supports the use of Mg²⁺ as a mechanism-based adjunct to opioids in neuropathic pain treatment.

This work was supported by the Medical University of Warsaw, Poland (grant number: FW3/3/F/MG/N/21).