Colonic irritation in the rat sensitizes urinary bladder afferents to mechanical and chemical stimuli: an afferent origin of pelvic organ cross-sensitization

Abstract

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.

Convergence of bladder and colon sensory innervation occurs at the primary afferent level

“…As we have recently shown, cross-organ pelvic reflexes, as well as, cross-organ alterations in physiological functioning and sensation following irritation (bladder-to-bowel and vice versa), suggested the involvement of pre-existing dichotomous afferent pathways in the pelvis (Pezzone et al 2005). This putative role of afferent pathways was further verified by single unit recordings of C-fiber bladder afferents within the pelvic nerve that exhibited sensitized mechanical and chemogenic response properties following acute colonic irritation with trinitrobenzenesulfonic acid (TNBS) (Ustinova et al 2006). Moreover, interruption of extrinsic neural input to the bladder ameliorated this effect, further confirming a neurogenic process originating in the colon.…”

“…Moreover, interruption of extrinsic neural input to the bladder ameliorated this effect, further confirming a neurogenic process originating in the colon. Thus, it was concluded that bowel-to-bladder, cross-organ afferent sensitization may occur peripherally, via antidromic axon reflexes from a single dichotomizing primary afferent supplying both the bowel and bladder as well as centrally via spinal or supraspinal circuits (Ustinova et al 2006).…”

“…We recently provided evidence of pre-existing neural pathways in the development of pelvic organ cross-sensitization by demonstrating that colonic hypersensitivity develops following the induction of acute cystitis and vice versa (Pezzone et al 2005). Follow-up studies in our laboratory employing single unit C-fiber bladder afferent recording revealed that acute colonic irritation is capable of sensitizing urinary bladder afferents to mechanical and chemical stimuli, and interruption of the neural input to the bladder can ameliorate this effect, suggesting a direct afferent pathway from the colon (Ustinova et al 2006). …”

Novel spinal pathways identified by neuronal c-Fos expression after urethrogenital reflex activation in female guinea pigs

“…Anatomically, there is a considerable degree of overlap and interaction between neural pathways to different pelvic organs (eg. rectum and urogenital system) with considerable potential for integration or modulation of their activity within the spinal cord (Berkley, 2006;Pezzone et al, 2005;Rudick et al, 2007;Ustinova et al, 2006;Ustinova et al, 2010).…”

Chiropractic care of interstitial cystitis/painful bladder syndrome associated with pelvic lumbar spine dysfunction: a case series

“…[9][10][11][12] However, a complete understanding of the autonomic control of the human bladder is still elusive. 8,13 The divergent nature of the autonomic nervous system in the pelvic region creates a complex pattern of altered neurophysiology, and evidence has been documented to show the presence of cross-system viscera-visceral interactions, that is, bladder inflammation having a direct influence on uterine or colon contractions/inflammations, and vice versa.…”