Experimental Gestational Diabetes Mellitus Prolongs Post-Incisional Mechanical Hypersensitivity and Increases...

Gestational diabetes mellitus (GDM) can lead to health complications in adult offspring. It was recently reported that experimental GDM increases intraepidermal nerve fiber density (INFD) in adult mouse offspring. However, the impact of GDM on acute postsurgical pain and the neuroimmune response to incision has not been examined.

GDM was induced through intraperitoneal administrations of streptozotocin (STZ) in ICR pregnant mouse dams. At 12 weeks old, all female mouse offspring underwent an incision in the glabrous skin of the right hindpaw. The mechanical sensitivity of both incised and non-incised hindpaws was assessed before and during the 3 weeks following the incision. At 16 weeks old, offspring born from dams with and without STZ-induced GDM were euthanized and processed for immunohistochemistry. The INFD (CGRP⁺ and PGP9.5⁺ axons) and the density of CD68⁺ macrophages around the wounded skin were quantified.

Offspring mice of dams with STZ-induced GDM exhibited decreased body weight, yet their blood glucose levels were comparable to those of offspring born from vehicle-treated dams. These offspring of dams with STZ-induced GDM experienced significantly prolonged incision-induced mechanical hypersensitivity compared to offspring of control dams. At 3 weeks post-incision, offspring of STZ-treated dams had an increased density of macrophages and greater INFD of CGRP⁺ and PGP9.5⁺ axons compared to the values of offspring of vehicle-treated dams.

Offspring of dams with STZ-induced GDM exhibited a delayed resolution of post-incisional pain that was accompanied by increased epidermal nerve fiber density and peri-incisional macrophage activation.