Iranian Journal of

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Background: Neuroinflammation and oxidative stress play a pivotal role in the diabetic neuropathic pain. The aim of this study was to evaluate the effect of aerobic exercise with melatonin on RAGE gene expression and some indicators of oxidative stress in rats with diabetic neuropathic pain
Methods: Forty 8-week-old male Wistar rats (weight range 204 ± 11.3 g) were randomly divided into five of 8 groups including: diabetic neuropathy (50 mg / kg streptozotocin intraperitoneal injection), diabetic melatonin neuropathy (mg / kg 10 melatonin daily for 6 weeks), diabetic neuropathy exercise (30 minutes of aerobic exercise at 15 meters per minute, 5 days a week for 6 weeks), diabetes melatonin neuropathy and healthy exercise and control. After confirmation of diabetic neuropathy by behavioral tests, exercise protocol and supplementation were performed. RAGE gene expression was measured by real-time technique and oxidative stress indices in spinal cord tissue by spectrophotometer. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis.
Results: Exercise and melatonin reduced the sensitivity of the nervous system to thermal hyperalgesia and mechanical allodynia. Aerobic exercise with melatonin significantly reduced RAGE gene expression and MAD concentration and increased the activity of SOD and CAT enzymes compared to the diabetic neuropathy group (P <0.05).
Conclusion: Aerobic exercise with melatonin modulates the expression of RAGE gene and oxidative stress indices and improves the sensitivity of nociceptors to pain factors. It is recommended to use aerobic exercise with melatonin for diabetics to reduce neuropathic pain.

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Desmond et al. (2025) have recently shown that subcutaneous injections of Mycobacterium vaccae ATCC 15483(M. vaccae) in adolescent male mice significantly prevented excessive weight gain and visceral adiposity induced by a Western-style diet. Despite no change in gut microbiota diversity, this intervention lowered hippocampal neuroinflammation markers (Nfkbia, Nlrp3) and anxiety-like behaviors. Since more than one billion people worldwide and about 30% of Iranian population are influenced by obesity, and this disease caused one in eight deaths from noncommunicable diseases in 2024, these microbiome-based strategies could have clinical value. Such approaches that target immunometabolic pathways represent a promising and interdisciplinary strategy that integrates endocrinology, microbiology, and the psychosomatic aspects of metabolic disorders. Nevertheless, M. vaccae media portrayal as an obesity vaccine causes misunderstanding. This treatment reduces, but does not completely hinder, diet-associated weight gain and could not be replaced with healthy diet habits. However, it could be considered as a supplementary approach to reduce the adverse effects of ultra-processed food consumption and could potentially augment existing obesity treatments, such as microbiome-based interventions, pharmaceutical therapies, and bariatric surgery. More extensive clinical trials are required to determine human efficacy, optimal dosing, safety, and integration with current obesity therapies.