Background: Even though inflammation is a traditional tool for the induction of hyperalgesia in many tissues, recent observations suggest that not all inflammatory processes produce this change. Tolerance to colorectal distension (CRD) is reduced in patients with acute ulcerative colitis but is increased in patients with chronic inflammatory bowel disease. This suggests that the nature of the inflammatory infiltrate influences visceral perception.
Aim: To test this hypothesis by assessing responses to CRD in mice with mild, acute or chronic colitis.
Methods: CRD responses were measured in mice with mild non-specific colitis, and dextran sodium sulphate (DSS)-induced acute and chronic colitis. Responses were compared with tissue infiltrate and damage, interleukin (IL)1β and myeloperoxidase (MPO) activity and substance P, β-endorphin and μ opioid receptor (MOR) expression.
Results: Mild and acute colitis were associated with increased responsiveness to CRD. In contrast, CRD responses were not increased in mice with chronic colitis and this difference was not due to altered colonic wall compliance. MPO and IL1β levels were greater in acute than in chronic colitis. Larger increases in tissue substance P were seen in acute than in chronic DSS, whereas CD4 T cells, β-endorphin and MOR expression were evident only in chronic colitis. An inverse correlation was seen between substance P and MOR in these tissues.
Conclusions: Acute colitis increased responsiveness to CRD and is accompanied by an acute inflammatory infiltrate and increased tissue substance P. Chronic DSS is accompanied by an increase in β-endorphin and MOR expression, and CD4 T cells, but no change in compliance or CRD responses. We conclude that acute inflammation generates hyperalgesia, whereas chronic inflammation involves infiltration by lymphocytes accompanied by MOR and β-endorphin up regulation, and this provides an antinociceptive input that restores normal visceral perception.
- CRD, colorectal distension
- DSS, dextran sodium sulphate
- EMG, electromyograph
- ENS, enteric nervous system
- IBD, inflammatory bowel disease
- MPO, myeloperoxidase
- MOR, μ opioid receptor
- NSC, non-specific colitis
- SCID, severe combined immune deficient
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Published Online First 3 October 2006
Funding: This work has been supported by a grant from the Canadian Institutes of Health Research (CIHR) to SMC and by a CIHR/Canadian Digestive Disease Foundation Doctoral Research Award to MVG.
Competing interests: None.
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