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Effect of Experimental Gestational Diabetes Mellitus on Mechanical Sensitivity, Capsaicin-Induced Pain Behaviors and Hind Paw Glabrous Skin Innervation of Male and Female Mouse Offspring

  • Munoz-Islas, Enriqueta1
  • Elizondo-Martinez, Cecilia Esther1
  • Gutierrez-Lopez, Mariela1
  • Acosta-Gonzalez, Rosa Issel1
  • Zaga-Clavellina, Veronica2
  • Helguera-Repetto, Addy Cecilia3
  • Ramirez-Rosas, Martha Beatriz1
  • Romero-Sandoval, E Alfonso4
  • Jimenez-Andrade, Juan Miguel1
  • 1 Unidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, Reynosa, Tamaulipas , (Mexico)
  • 2 Departamento de Fisiología y Desarrollo Celular, Instituto Nacional de Perinatología, Ciudad de México , (Mexico)
  • 3 Departamento de Inmunobioquímica, Instituto Nacional de Perinatología, Ciudad de México , (Mexico)
  • 4 Department of Anesthesiology, Wake Forest University School of Medicine, Winston Salem, NC
Published Article
Journal of Pain Research
Dove Medical Press
Publication Date
Jun 02, 2021
DOI: 10.2147/JPR.S313467
PMID: 34103982
PMCID: PMC8180275
PubMed Central
  • Original Research


Purpose Gestational diabetes mellitus (GDM) induces cardiovascular and metabolic disturbances in offspring. However, the effects of GDM in pain processing in offspring and whether male and female offspring are equally affected is not well known. Thus, we determined: i) whether GDM in mice affects offspring hindpaw mechanical sensitivity, capsaicin-induced spontaneous pain-like behaviors, and epidermal nerve fiber density (ENFD); and ii) whether there is sexual dimorphism in these parameters in offspring from GDM dams. Methods GDM was induced in pregnant ICR mice via i.p. streptozotocin (STZ). Then, glucose levels from dams and offspring were determined. Male and female offspring 2–3 months of age were evaluated for: a) baseline mechanical sensitivity of the hind paw by using von Frey filaments; b) number of flinches and time spent guarding induced by intraplantar capsaicin (0.1%); and c) density of PGP-9.5 and CGRP axons in the epidermis from the hind paw glabrous skin. Results Prepartum levels of glucose in STZ-treated dams were significantly increased compared to vehicle-treated dams; however, GDM or vehicle offspring displayed normal and similar blood glucose levels. Male and female GDM offspring showed significantly greater mechanical sensitivity and capsaicin-induced pain behaviors compared to vehicle offspring. Male GDM offspring displayed a slightly more intense nociceptive phenotype in the capsaicin test. PGP-9.5 and CGRP ENFD in hind paw glabrous skin were greater in male and female GDM offspring versus their controls. Sexual dimorphism was generally not observed in GDM offspring in most of the studied parameters. Conclusion These results suggest GDM induced greater pain-like behaviors in adult offspring regardless of sex along with an increased ENFD of PGP-9.5 and CGRP in the hind paw glabrous skin. We show that GDM peripheral neuropathy differs from diabetic peripheral neuropathy acquired in adulthood and set the foundation to further study this in human babies exposed to GDM.

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