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

J. Chen, John Winston, S. K. Sarna

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)469-478
Number of pages10
JournalNeuroscience
Volume248
DOIs
StatePublished - Sep 17 2013

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Hypersensitivity
Inflammation
Dextran Sulfate
Ulcerative Colitis
Afferent Neurons
Spinal Ganglia
Neurons
Messenger RNA
Brain-Derived Neurotrophic Factor
Nerve Growth Factor
Spinal Cord
Colon
Down-Regulation

Keywords

  • Abdominal pain
  • Chronic stress
  • Colon inflammation
  • Inflammatory bowel disease
  • Sensory neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neurological and cellular regulation of visceral hypersensitivity induced by chronic stress and colonic inflammation in rats. / Chen, J.; Winston, John; Sarna, S. K.

In: Neuroscience, Vol. 248, 17.09.2013, p. 469-478.

Research output: Contribution to journalArticle

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