Hyperexcitability of convergent colon and bladder dorsal root ganglion neurons after colonic inflammation: mechanism for pelvic organ cross-talk

Authors


Dr Anna Malykhina, Department of Physiology, University of Oklahoma, HSC, 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
Tel.: 405 271 2226, ext. 56256; fax: 405 271 3181;
e-mail: anna-malykhina@ouhsc.edu

Abstract

Abstract  Clinical studies reveal concomitant occurrence of several gastrointestinal and urologic disorders, including irritable bowel syndrome and interstitial cystitis. The purpose of this study was to determine the mechanisms underlying cross-organ sensitization at the level of dorsal root ganglion (DRG) after acute and subsided gastrointestinal inflammation. DiI (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate) and Fast Blue were injected into the distal colon and urinary bladder of male rats, respectively. Convergent DRG neurons were found in L1-L3 and L6-S2 ganglia with an average distribution of 14% ± 2%. The resting membrane potential (RMP) of cells isolated from upper lumbar (UL) ganglia was −59.8 ± 2.7 mV, whereas lumbosacral (LS) neurons were more depolarized (RMP = −49.4 ± 2.1 mV, P ≤ 0.05) under control conditions. Acute trinitrobenzene sulfonic acid (TNBS) colitis (3 days) decreased voltage and current thresholds for action potential firing in LS but not UL convergent capsaicin-sensitive neurons. This effect persisted for 30 days in the absence of overt colonic inflammation. The current threshold for action potential (AP) firing in UL cells was also decreased from 165.0 ± 24.5 pA (control) to 85.0 ± 19.1 pA at 30 days (P ≤ 0.05), indicating increased excitability. The presence of a subpopulation of colon-bladder convergent DRG neurons and their persistent hyperexcitability after colonic inflammation provides a basis for pelvic organ cross-sensitization.

Ancillary