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

Julie A. Christianson, Ruomei Liang, Elena E. Ustinova, Brian M. Davis, Matthew O. Fraser, Michael A. Pezzone
In: Pain · 2006 · vol. 128(3) , pp. 235–243 · doi:10.1016/j.pain.2006.09.023 · PMID:17070995 · W2139416059
article OA: green CC0 ⤵ 12 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This study found that a significant percentage of dorsal root ganglion neurons in rats and mice innervate both the bladder and distal colon, indicating a neuronal basis for cross-organ sensitization.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This study investigated whether bladder and distal colon sensory neurons share pre-existing “dichotomizing” pathways by performing concurrent retrograde labeling of urinary bladder and distal colon afferents in male Sprague-Dawley rats and C57Bl/6 mice using Alexa Fluor–conjugated cholera toxin subunit B, followed by confocal quantification of CTB-positive dorsal root ganglion (DRG) neurons. The authors found that in rats, bladder-derived CTB-positive afferents were nearly three times more numerous than colon-derived ones, whereas in mice both organs contributed equally, and that in both species most afferents arose from lumbosacral and secondarily from thoracolumbar ganglia. They further reported substantial dual labeling consistent with dichotomizing afferents (17% in rats; 21% in mice), with most dually labeled neurons localized primarily to LS ganglia and some to TL. A key limitation is that dual labeling was inferred at the level of DRG neurons rather than directly demonstrating functional synaptic or circuit-level convergence beyond retrograde uptake. This paper is centrally about endometriosis— it is included in the corpus because it discusses pelvic organ cross-sensitization pathways relevant to overlapping pelvic pain disorders, which are commonly associated with endometriosis, even though endometriosis is not directly studied.

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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, CTB-positive afferents retrogradely labeled from the bladder were nearly three 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.

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