Dichotomizing afferents are individual dorsal root ganglion (DRG) neurons that innervate two distinct structures thereby providing a form of afferent convergence that may be involved in pelvic organ cross-sensitization. To determine the distribution of dichotomizing afferents supplying the distal colon and bladder of the Sprague-Dawley rat and the C57Bl/6 mouse, we performed concurrent retrograde labeling of urinary bladder and distal colon afferents using cholera toxin subunit B (CTB) fluorescent conjugates. Animals were perfused 4-5 days after sub-serosal organ injections, and the T10-S2 DRG were removed, sectioned, and analyzed using confocal microscopy. In the rat, CTBpositive afferents retrogradely labeled from the bladder were nearly 3 times more numerous than those labeled from the distal colon, while in the mouse, each organ was equally represented. In both species, the majority of colon and bladder afferents projected from lumbosacral (LS) ganglia and secondarily from thoracolumbar (TL) ganglia. In the rat, 17% of the total CTB-positive neurons were retrogradely labeled from both organs with 11% localized in TL, 6% in LS, and 0.8% in thoracic (TH) ganglia. In the mouse, 21% of the total CTB-positive neurons were dually-labeled with 12% localized in LS, 4% in TH, and 4% in TL ganglia. These findings support the existence of dichotomizing pelvic afferents, which provide a pre-existing neuronal substrate for possible immediate and maintained pelvic organ cross-sensitization and ultimately may play a role in the overlap of pelvic pain disorders.
Chronic pelvic pain (CPP) disorders frequently overlap. We have demonstrated that acute and chronic colonic irritation can lead to neurogenic cystitis. We hypothesize that acute colonic irritation can sensitize urinary bladder afferents to mechanical and chemical stimuli. Single-unit afferent activity was recorded from fine filaments of the pelvic nerve in urethane-anesthetized Sprague-Dawley female rats before and 1 h after intracolonic administration of trinitrobenzenesulfonic acid (TNBS). Only spontaneously active afferents with receptive fields in the bladder and conduction velocities <2.5 m/s (unmyelinated C-fibers) were studied. Mechanical sensitivity was tested by bladder distension (BD) during saline infusion, whereas chemical sensitivity was tested with intravesical capsaicin, bradykinin, or substance P. Colonic irritation increased the resting firing rate of bladder afferents twofold (1.0 +/- 0.2 vs. 0.49 +/- 0.2 impulses/s, P < 0.05). Moreover, at low-pressure BDs (10-20 mmHg), a greater percentage of afferents exhibited increased activity following TNBS (73 vs. 27%, P < 0.05). Although the magnitude of the afferent response to BD was unchanged at low pressures, the response was greatly enhanced at pressures 30 mmHg and above (2.36 +/- 0.56 vs. 8.55 +/- 0.73 impulses/s, P < 0.05). Responses to capsaicin, bradykinin, and substance P were also significantly enhanced following TNBS, and all responses were blocked by bladder denervation. In rats, colonic irritation sensitizes urinary bladder afferents to noxious mechanical and chemical stimuli. Interruption of the neural input to the bladder minimized this effect, suggesting a local afferent pathway from the colon. Thus, the overlap of CPP disorders may be a consequence of pelvic afferent cross-sensitization.
ObjectiveTo investigate local inflammatory events within the colonic muscularis as a causative factor of postoperative ileus. Summary Background DataSurgically induced intestinal muscularis inflammation has been hypothesized as a mechanism for postoperative ileus. The colon is a crucial component for recovery of gastrointestinal motor function after surgery but remains unaddressed. The authors hypothesize that colonic manipulation initiates inflammatory events that directly mediate postoperative smooth muscle dysfunction. MethodsRats underwent colonic manipulation. In vivo transit and colonic motility was estimated using geometric center analysis and intraluminal pressure monitoring. Leukocyte extravasation was investigated in muscularis whole mounts. Mediator mRNA expression was determined by real-time reverse transcriptase-polymerase chain reaction. In vitro circular muscle contractility was assessed in a standard organ bath. The relevance of iNOS and COX-2 inhibition was determined using DFU or L-NIL perfusion. ResultsColonic manipulation resulted in a massive leukocyte recruitment and an increase in inflammatory mRNA expression. This inflammatory response was associated with an impairment of in vivo motor function and an inhibition of in vitro smooth muscle contractility (56%). L-NIL but not DFU significantly ameliorated smooth muscle dysfunction. ConclusionsThe results provide evidence for a surgically initiated local inflammatory cascade within the colonic muscularis that mediates smooth muscle dysfunction, which contributes to postoperative ileus.Iatrogenic postoperative gastrointestinal dysmotility remains a near-canonical outcome of abdominal surgery. The occurrence of ileus-related complications as well as the "typical" delayed postoperative recovery of intestinal motor activity is associated with a prolonged hospital stay and increased perioperative expense, which has a significant economic impact. 1-3Inhibitory neural reflexes and local inflammatory events within the intestinal muscularis have been proposed to participate in the development of postoperative motility changes. 2,4,5 We have previously shown that surgical manipulation of the small intestine results in the activation of resident muscularis macrophages, which is followed by a massive extravasation of immunocompetent cells into the intestinal muscularis.5 This inflammatory response correlates with the postoperative suppression in jejunal smooth muscle contractile activity.6 However, the resumption of gastrointestinal motility is dependent on the functional cooperation of the entire gastrointestinal tract, and the recovery of the small intestine may arguably not be the crucial gastrointestinal component of surgically induced ileus.
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