Metformin protects from Oxaliplatin-induced loss of intraepidermal nerve fibers density (IENFD). (A and B) Rats were treated with oxaliplatin (4 mg/Kg i.p. for 2 consecutive days per week), metformin (250 mg/Kg daily i.p.), or both drugs together for 4 weeks. The skin from the paw was removed and immunostained against PGP9.5 (a pan neuronal marker) to quantify the number of nerve fibres crossing into the epidermis per mm (C: Stratum Corneum; E: Epidermis; D: Dermis, Scale bar, 20 μm). (Control n = 4; Met n = 10, Oxal n = 10, Oxal + Met n = 10), *** ***p < 0,001 One-Way ANOVA, Bonferroni’s post-hoc test.) (C and D) Sciatic nerves from rats treated with oxaliplatin, metformin, or both drugs were collected, transversally cut and immunostained against anti-neurofilament heavy subunit (NF-H). Axonal density was quantified using epifluorescence reactivity of the neurofilament marker Scale bar, 100 μm- Mean ± SEM, One-Way ANOVA, Bonferroni’s post-hoc test.