Impairments of the primary afferent nerves in a rat model of diabetic visceral hyposensitivity

Mol Pain. 2015 Dec 10:11:74. doi: 10.1186/s12990-015-0075-5.

Abstract

Background: Diabetic neuropathy in visceral organs such as the gastrointestinal (GI) tract is still poorly understood, despite that GI symptoms are among the most common diabetic complications. The present study was designed to explore the changes in visceral sensitivity and the underlying functional and morphological deficits of the sensory nerves in short-term diabetic rats. Here, we compared the colorectal distension (CRD)-induced visceromotor response (VMR, an index of visceral pain) in vivo, the mechanosensitivity of colonic afferents ex vivo as well as the expression of protein gene product (PGP) 9.5 and calcitonin gene-related peptide (CGRP) in colon between diabetic (3-6 weeks after streptozotocin injection) and control (age-matched vehicle injection) rats.

Results: VMR was markedly decreased in the diabetic compared to the control rats. There was a significant decrease in multiunit pelvic afferent nerve responses to ramp distension of the ex vivo colon and single unit analysis indicated that an impaired mechanosensitivity of low-threshold and wide dynamic range fibers may underlie the afferent hyposensitivity in the diabetic colon. Fewer PGP 9.5- or CGRP-immunoreactive fibers and lower protein level of PGP 9.5 were found in the colon of diabetic rats.

Conclusions: These observations revealed the distinctive feature of colonic neuropathy in short-term diabetic rats that is characterized by a diminished sensory innervation and a blunted mechanosensitivity of the remnant sensory nerves.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / genetics
  • Colon / innervation
  • Colon / physiopathology
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Experimental / physiopathology
  • Gene Expression Regulation
  • Male
  • Neurons, Afferent / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Ubiquitin Thiolesterase / genetics
  • Viscera / physiopathology

Substances

  • UCHL1 protein, rat
  • Ubiquitin Thiolesterase
  • Calcitonin Gene-Related Peptide