Experimental colitis in mice and sensitization of converging visceral and somatic afferent pathways

Abstract

Chronic pain syndromes affecting different organs often coexist. We hypothesized that sensitization of one afferent pathway may affect converging input from other areas of the body. We induced colitis in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS); control animals were treated with equal volumes of vehicle (50% ethanol) only. Visceromotor responses to graded colorectal distension, cystometrograms, and response thresholds to mechanical and thermal stimulation of both hind paws were determined on days 7 and 14. Inflammation of colon and bladder was assessed with validated histological markers and scores. TNBS caused significant colitis on day 7 that resolved by day 14; there was no evidence of bladder inflammation. There was a significant hypersensitivity to colorectal distension on day 7, which returned to normal on day 14. This was associated with bladder overactivity, as demonstrated by early onset of micturition and more frequent micturition on day 7 after TNBS administration. Colitis also significantly altered responses to mechanical and thermal stimulation of both hind paws on day 7 but not day 14. We conclude that cross talk between afferent visceral and somatic pathways may contribute to the coexistence of pain syndromes.

Cross-organ interactions between reproductive, gastrointestinal, and urinary tracts: modulation by estrous stage and involvement of the hypogastric nerve

“…Acute bladder inflammation also reduces the efficacy of cannabinoid agonists on the uterine horn (21). In addition, others have recently reported that acute cystitis increases abdominal wall muscle activity that is evoked by distention of the untreated colon (55) and, conversely, that acute, as well as chronic, colon irritation induces bladder overactivity (41,55).…”

“…The estrous influences on the cross-system effects observed here suggest that the effects are influenced by ovarian hormones, possibly estradiol. Although most previous studies of cross-organ influences between the colon and bladder have not investigated such influences (e.g., 41,43,54,55,57), the present results are consistent with findings showing that the severity of vaginal hyperalgesia induced by abdominal endometriosis correlates with circulating levels of estradiol (18). In that study, the hyperalgesia was greatest in proestrus (high level of estradiol and low level of progesterone) and was completely alleviated in estrus (very low estradiol and progesterone), a result similar to that observed here.…”

“…Thus acute bladder inflammation in rats increases the motility of the uninflamed uterus (22) and reduces the efficacy of drugs on the uninflamed uterus (21). In addition, acute inflammation of the rat colon or prostate, as well as chronic abdominal pathology (surgically induced endometriosis) produces signs of inflammation in the otherwise healthy bladder (18,41,50,55,71). Furthermore, the chronic condition of surgically induced endometriosis in rats increases pain behaviors produced by a ureteral stone (26) and induces vaginal hyperalgesia (18).…”

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

“…Moreover, infection with the nematode Trichinella spiralis led to an increase in visceral sensitivity to pain for several weeks after the inflammation had subsided (1). However, the development of postinflammatory hyperalgesia after a transient inflammation in mice was not observed with TNBS, acetic acid, capsaicin, or mustard oil (20,23). It is not known yet whether DSS-induced colitis also causes postinflammatory visceral hyperalgesia.…”

Glutamate Transporter Activators as Anti-Nociceptive Agents

“…The most common technique used in pre-clinical study of visceral nociception is the visceromotor response to hollow organ distension, described in detail elsewhere [15].…”