Fig. 7: Genetic reconstitution of POMC and MOR rescues thermal hyperalgesia in diabetic mice. | Nature Communications

Fig. 7: Genetic reconstitution of POMC and MOR rescues thermal hyperalgesia in diabetic mice.

From: Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy

Fig. 7

a Thermal hypersensitivity measured using Hargreaves test in naïve controls (non-diabetic, non-AAV injected) and diabetic mice overexpressing rAAV-1/2 constructs only in their right (ipsilateral) L3 and L4 DRG. Readings taken before and after intraplantar injection of PKC inhibitor in both hindpaws (Gö6983, 20 μM, 45 min) (naïve control, n = 10; D + GFP, n = 9; D + MOR, n = 10; D + POMC, n = 9; D + POMC-MOR, n = 10). b Schematic representation of intrathecal injection in diabetic mice with rAAV-9/2 constructs for overexpressing GFP or POMC-MOR. Readings taken before and after intraplantar injection of PKC inhibitor in both hindpaws (Gö6983, 20 μM, 45 min). c Immunostaining of DRG with GFP- or FLAG-specific antibodies after intrathecal injection showing expression of the viral constructs (n = 9–10 mice/group). d Thermal hypersensitivity measured using Hotplate test in naïve controls and diabetic mice overexpressing rAAV-9/2 constructs (naïve control, n = 10; D + GFP, n = 9; D + POMC-MOR, n = 9). PWL = paw withdrawal latency. For all panels, female mice data are shown. The boxplot in panels (a) and (d) corresponds to median, 25th, and 75th percentiles, whiskers correspond to minimum and maximum values; two-way ANOVA followed by Tukey’s post-hoc test; *p = 0.040, **p < 0.01, ***p < 0.0001 with 95% C.I. Cyan bar: D + GFP, green bar: D + MOR, blue bar: D + POMC, red bar: D + POMC-MOR. Scale = 50 µm. Source data are provided as a Source Data file.

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