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Neuroscience. 2013 Sep 17;248:469-78. doi: 10.1016/j.neuroscience.2013.06.024. Epub 2013 Jun 24.

Neurological and cellular regulation of visceral hypersensitivity induced by chronic stress and colonic inflammation in rats.

Author information

1
Enteric Neuromuscular Disorders and Visceral Pain Center, Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-1083, United States.
2
Enteric Neuromuscular Disorders and Visceral Pain Center, Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-1083, United States; Enteric Neuromuscular Disorders and Visceral Pain Center, Division of Gastroenterology, Department of Neuroscience, and Cell Biology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-1083, United States. Electronic address: sksarna@utmb.edu.

Abstract

The role of inflammation in inducing visceral hypersensitivity (VHS) in ulcerative colitis patients remains unknown. We tested the hypothesis that acute ulcerative colitis-like inflammation does not induce VHS. However, it sets up molecular conditions such that chronic stress following inflammation exaggerates single-unit afferent discharges to colorectal distension. We used dextran sodium sulfate (DSS) to induce ulcerative colitis-like inflammation and a 9-day heterotypic chronic stress protocol in rats. DSS upregulated Nav1.8 mRNA in colon-responsive dorsal root ganglion (DRG) neurons, TRPV1 in colonic muscularis externae (ME) and BDNF in spinal cord without affecting the spike frequency in spinal afferents or VMR to CRD. By contrast, chronic stress did not induce inflammation but it downregulated Kv1.1 and Kv1.4 mRNA in DRG neurons, and upregulated TRPA1 and nerve growth factor in ME, which mediated the increase of spike frequency and VMR to CRD. Chronic stress following inflammation exacerbated spike frequency in spinal afferent neurons. TRPA1 antagonist suppressed the sensitization of afferent neurons. DSS-inflammation did not affect the composition or excitation thresholds of low-threshold and high-threshold fibers. Chronic stress following inflammation increased the percent composition of high-threshold fibers and lowered the excitation threshold of both types of fibers. We conclude that not all types of inflammation induce VHS, whereas chronic stress induces VHS in the absence of inflammation.

KEYWORDS:

abdominal pain; chronic stress; colon inflammation; inflammatory bowel disease; sensory neurons

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