Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunction.
OBJECTIVE
We established the concept that transient enteric infection may lead to persistent gut dysfunction, evident in vitro, in nematode-infected mice. The present study determined whether gut dysfunction in this model involves motor and sensory changes reminiscent of changes found in patients with postinfective irritable bowel syndrome (PI-IBS) and investigated underlying mechanisms.


METHODS
Mice infected up to 70 days previously with Trichinella spiralis (Tsp) underwent videofluoroscopy with image analysis to assess upper gastrointestinal motility. Pseudoaffective responses to colorectal distention (CRD) were assessed using a barostat and validated by single fiber recordings from spinal nerves during CRD. Tissues were examined at different time points for histology, immunohistochemistry, and cytokine analysis. Some mice received dexamethasone intraperitoneally on days 23-25 PI or Tsp antigen orally on days 29, 43, and 57 PI.


RESULTS
From day 28 PI, no discernible inflammation was present in the gut. Frequency and propagation velocity of intestinal contractions decreased, and retroperistalsis increased at days 28 to 42 PI. CRD induced an allodynic and hyperalgesic response in PI mice, which was accompanied by increased single unit discharge. Gavage of Tsp antigen induced T-cell responses and sustained gut dysfunction for 70 days PI. Administration of dexamethasone postinfection normalized dysmotility and visceral hyperalgesia.


CONCLUSIONS
Long-lasting gut dysmotility and hyperalgesia develop in mice after transient intestinal inflammation. These changes are maintained by luminal exposure to antigen and reversed by corticosteroid treatment. The findings prompt consideration of this as a model of PI-IBS.
Bercík
Premysl
P
Department of Medicine, McMaster University, Hamilton, Ontario, Canada. bercikp@mcmaster.ca
Wang
Lu
L
Verdú
Elena F
EF
Mao
Yukang K
YK
Blennerhassett
Patricia
P
Khan
Waliul I
WI
Kean
Iain
I
Tougas
Gervais
G
Collins
Stephen M
SM
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use; D000947:Antigens, Helminth / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D005769:Gastrointestinal Motility / Q000276:immunology; D006930:Hyperalgesia / Q000188:drug therapy / Q000469:parasitology / Q000503:physiopathology; D043183:Irritable Bowel Syndrome / Q000188:drug therapy / Q000469:parasitology* / Q000503:physiopathology; D051379:Mice; D023421:Models, Animal; D017160:Trichinella spiralis / Q000276:immunology*; D014235:Trichinellosis / Q000150:complications / Q000276:immunology* / Q000503:physiopathology
D000890:Anti-Infective Agents; D000947:Antigens, Helminth; D017252:CD3 Complex; D016207:Cytokines; D003907:Dexamethasone