Journal of pain research · 2026
A Rat Model Mimicking Treatment-Induced Painful Diabetic Neuropathy Following Experimental Rapid Weight Loss.
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Liu Yunwei, Cui Chongsong, Peng You, Zhang Yaqi, Zhong Tuoling, Zhang Hang, Liang Qingshun, Liu Zhenjie
Аннотация
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.
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.