Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation

Jinghong Chen, John H. Winston, Yu Fu, Jutatip Guptarak, Kathryn L. Jensen, Xuan Zheng Shi, Thomas A. Green, Sushil K. Sarna

Research output: Contribution to journalArticlepeer-review


Psychological disorders are prevalent in patients with inflammatory bowel disease; the underlying mechanisms remain unknown. We tested the hypothesis that ulcer-ative colitis-like inflammation induced by dextran sodium sulfate (DSS) exacerbates the ongoing spontaneous activity in colon-projecting afferent neurons that induces abdominal discomfort and anxiety, and depressive-like behaviors in rats. In this study, we used the conditioned place preference and standard tests for anxiety- and depression-like behaviors. DSS rats developed anxiety- and depression-like behaviors 10 to 20 days after the start of inflammation. Single-fiber recordings showed an increase in the frequency of spontaneous activity in L6-S1 dorsal root ganglion (DRG) roots. Prolonged desensitization of transient receptor potential vanilloid 1 (TRPV1)-expressing colonic afferents by resiniferatoxin (RTX) suppressed the spontaneous activity, as well as the anxiety- and depressive-like behaviors. Reduction in spontaneous activity in colon afferents by intracolonic administration of lidocaine produced robust conditioned place preference (CPP) in DSS rats, but not in control rats. Patch-clamp studies demonstrated a significant decrease in the resting membrane potential, lower rheobase, and sensitization of colon-projecting L6-S1 DRG neurons to generate trains of action potentials in response to current injection in DSS rats. DSS inflammation upregulated the mRNA levels of transient receptor potential ankyrin 1 and TRPV1 channels and downregulated that of Kv1.1 and Kv1.4 channels. Ulcerative colitis-like inflammation in rats induces anxiety-and depression-like behaviors, as well as ongoing abdominal discomfort by exacerbating the spontaneous activity in the colon-projecting afferent neurons. Alterations in the expression of voltage- and ligand-gated channels are associated with the induction of mood disorders following colon inflammation.

Original languageEnglish (US)
Pages (from-to)R18-R27
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number1
StatePublished - Jan 1 2015


  • Anxiety
  • Depression
  • Inflammatory bowel disease
  • Spontaneous activity in visceral afferent neurons
  • Visceral hypersensitivity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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