Chronic pelvic pain of unknown etiology is a common disorder, particularly in women. It has been documented that compared to healthy controls, patients with gastrointestinal diseases including irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) often complain of urinary symptoms such as nocturia, frequency and urgency of micturition. This may be the result of cross-sensitization between the colon and bladder. In this exploratory proposal we seek to define the changes in the neural processing and bladder smooth muscle function in a model of colonic hypersensitivity. Preliminary studies indicate the presence of convergent pre-spinal neurons that receive input from both the bladder and colon.
Specific Aim 1 is to determine the changes in electrical excitability and the ionic currents of these primary sensory neurons following acute colonic inflammation with TNBS instillation and after recovery. Colonic hypersensitivity in the recovery state will be examined by measuring the visceromotor reflex. Cell bodies in the dorsal root ganglia (DRG) of the L6-S2 lumbosacral region will be retrogradely labeled with tracer dyes injected into the colon and bladder. Cell excitability will be determined using patch-clamp techniques in identified DRG cells of the bladder and colon and those that co-label.
Specific Aim 2 will be to determine the changes in the properties of spinal neurons that demonstrate convergence between the bladder and colon. In this aim, we will determine the modulation of the threshold sensitivity and duration of impulses by colonic inflammation and following recovery.
Specific Aim 3 will be to identify the changes in the bladder smooth muscle by colonic inflammation and during hypersensitive state with no overt colonic inflammation. We will measure the contractility of detrusor muscle strips and changes in the mRNA of pro-inflammatory cytokines. The findings from these studies will allow for formulation of hypotheses regarding neural processing and molecular changes in cross-sensitization between the bladder and colon.
| Qin, C; Malykhina, A P; Akbarali, H I et al. (2008) Acute colitis enhances responsiveness of lumbosacral spinal neurons to colorectal distension in rats. Dig Dis Sci 53:141-8 |
| Malykhina, A P; Qin, C; Greenwood-van Meerveld, B et al. (2006) Hyperexcitability of convergent colon and bladder dorsal root ganglion neurons after colonic inflammation: mechanism for pelvic organ cross-talk. Neurogastroenterol Motil 18:936-48 |
