Visceral pain perception is determined by the duration of colitis and associated neuropeptide expression in the mouse

Abstract

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)1b and myeloperoxidase (MPO) activity and substance P, b-endorphin and m 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 IL1b 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, b-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 b-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 b-endorphin up regulation, and this provides an antinociceptive input that restores normal visceral perception.

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

“…Indeed patients with Crohn's disease and Ulcerative Colitis experience hyposensitivity to rectal balloon pressure, which has previously been attributed to alterations in the central nervous system processing and descending inhibitory nervous pathways (Bernstein et al, 1996;Chang et al, 2000). Our studies indicate immune derived β-endorphin may also provide inhibitory influences in IBD , as has been described in mouse models of colonic inflammation, however this is yet to be investigated in humans (Valdez-Morales et al, 2013;Verma-Gandhu et al, 2007).…”

Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice: spinal cord c-Fos expression and behavior

“…Another recent study, however, has shown that during acute DSS-induced colitis, male mice did develop increased responses toward noxious colonic distension (31). Moreover, in chronic DSS-induced colitis, induced by repetitive cycles of DSS administration to male mice, increased visceral perception did not occur (31).…”

“…Another recent study, however, has shown that during acute DSS-induced colitis, male mice did develop increased responses toward noxious colonic distension (31). Moreover, in chronic DSS-induced colitis, induced by repetitive cycles of DSS administration to male mice, increased visceral perception did not occur (31). Despite the conflicting results whether visceral hypersensitivity occurs during colitis, our present data clearly demonstrated that after resolution of DSS-induced colitis the visceral pain response to intracolonic capsaicin is increased.…”

“…Comparable to the different outcomes on visceral hyperalgesia during DSS-induced colitis (24,31), the occurrence of postinflammatory hyperalgesia after a transient inflammation does not seem to be a general phenomenon as well, since transient inflammation with TNBS or acetic acid, capsaicin, or mustard oil in mice did not produce long-lasting changes in visceral sensitivity (20,23). In the above-mentioned studies, the change in visceral hyperalgesia was determined by measuring the response to colorectal distension, which is thought to be regulated via changes in the sensitivity of low-threshold mechanosensitive visceral afferents that encode distending pressures into the noxious range (14).…”

Developmental expression of δ‐opioid receptors during maturation of the parasympathetic, sympathetic, and sensory innervations of the neonatal heart: Early targets for opioid regulation of autonomic control

“…They provide the organism with mechanisms to cope with environmental stress, such as mechanical stress, tissue injury, pathogen invasion, inflammation, tumor growth, and others (Schäfer, 2010). Opioid peptides and their receptors mediate a wide variety of effects including pain (Schäfer, 2010), gastrointestinal motility (Verma-Gandhu et al, 2007), respiration (Krajnik et al, 2009;Mahler et al, 2009), and cardiac function (Kasper et al, 1992;Barry and Zuo, 2005;Mousa et al, 2010). Pharmacologic and molecular studies have identified three opioid receptors: l (M), j-(K), and d (D) opioid receptors (ORs) (Schä-fer, 2010).…”