ArticleJournal of pain research2026
A Rat Model Mimicking Treatment-Induced Painful Diabetic Neuropathy Following Experimental Rapid Weight Loss.
Article in Journal of pain research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: This study investigated the feasibility of constructing a painful diabetic neuropathy (PDN) rat model mimicking treatment-induced neuropathy (TIND) through rapid weight reduction via caloric restriction combined with metformin. Methods: Type 2 diabetes was induced using a high-fat diet combined with low-dose streptozotocin (STZ, 30 mg/kg). At week 11, rats were classified into spontaneous PDN and non-painful diabetic neuropathy (NPDN) groups based on mechanical withdrawal threshold (MWT) decline (≥50% from baseline). Rapid weight loss was subsequently induced over 10 weeks (weeks 12-21) via 40% food restriction by weight combined with metformin gavage (200 mg/kg·d). Mechanical withdrawal threshold (MWT), motor and sensory nerve conduction velocities (MNCV and SNCV), sciatic nerve histopathology, and intraepidermal nerve fiber density (IENFD) were assessed. Results: The spontaneous PDN rate at week 11 was 54.8% (17/31). Following the intervention, MWT decreased by 91.47% in the NPDN-WL group (P = 0.001) and by 91.08% in the PDN-WL group (P < 0.01). MNCV was significantly lower in both diabetic weight-loss groups than in their respective diabetic control groups. SNCV was numerically lower in the weight-loss groups, but the corresponding pairwise differences were not statistically significant after Bonferroni adjustment. Histological examination showed myelin disorganization, vacuolar degeneration, and axonal swelling, whereas IENFD showed a non-significant decreasing trend. Notably, all NPDN-WL rats (7/7) achieved complete phenotypic conversion (100%), whereas no conversion occurred in the NPDN-Con group (0/3, 0%). However, the control groups were small and unbalanced (NPDN-Con, n = 3; PDN-Con, n = 4), and these findings should be interpreted with caution. Conclusion: These preliminary findings suggest that rapid weight reduction via caloric restriction combined with metformin may offer a feasible approach for establishing a TIND-like PDN rat model, and that rapid weight loss under diabetic conditions could be an important contributing factor in the conversion toward a painful neuropathy phenotype. Further studies with larger sample sizes are warranted to substantiate these observations.
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