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

Abstract

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.

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

“…The sensitization of visceral afferents, particularly after exposure to GPCR agonists, is a major mechanism through which postinflammatory visceral pain is initiated and maintained. Evidence for functional expression of TRPV1, TRPV4, TRPA1, and TRPM8 by colonic afferent neurons is provided by studies demonstrating mRNA and protein expression and by Ca 2+ imaging and electrophysiologic studies that show responsiveness by these neurons to established TRP channel activators (Christianson et al, 2007(Christianson et al, , 2010Brierley et al, 2008Brierley et al, , 2009De Schepper et al, 2008;Tan et al, 2008;Harrington et al, 2011).…”

Organ cross talk modulates pelvic pain

“…For example, mustard oil administered to the uterine horn or colon in female rats induced vascular permeability in the bladder consistent with inflammation at a site distinct from the inflammatory stimulus (41). This cross talk is at least partially bidirectional, because bladder irritation also sensitized the colon to distension stimuli (28), and this noxious effect can be mediated by either chemical or mechanical stimuli (11,34,35). It is not known whether neurogenic cystitis also involves cross talk, but these previous findings suggest that organ cross talk may be exploited for therapeutic approaches to pelvic pain.…”

Constipation in patients with myofascial pain syndrome as important aspect for clinical and nutritional treatment: A case-control study

“…Animal model studies suggest that crosssensitization where inflammation and visceral pain are centrally transmitted for processing via the spinothalamic may provide an explanation [16][17][18][19].…”