Pharmacologic attenuation of pelvic pain in a murine model of interstitial cystitis
1 Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
2 Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
BMC Urology 2009, 9:16 doi:10.1186/1471-2490-9-16Published: 12 November 2009
Interstitial cystitis/painful bladder syndrome (IC/PBS) is a bladder disease that causes debilitating pelvic pain of unknown origin, and IC/PBS symptoms correlate with elevated bladder lamina propria mast cell counts. Similar to IC/PBS patients, pseudorabies virus (PRV) infection in mice induces a neurogenic cystitis associated with bladder lamina propria mast cell accumulation and pelvic pain. We evaluated several drugs to determine the effectiveness of reducing PRV-induced pelvic pain.
Neurogenic cystitis was induced by the injection of Bartha's strain of PRV into the abductor caudalis dorsalis tail base muscle of female C57BL/6 mice. Therapeutic modulation of pelvic pain was assessed daily for five days using von Frey filament stimulation to the pelvic region to quantify tactile allodynia.
Significant reduction of PRV-induced pelvic pain was observed for animals treated with antagonists of neurokinin receptor 1 (NK1R) and histamine receptors. In contrast, the H1R antagonist hydroxyzine, proton pump inhibitors, a histamine receptor 3 agonist, and gabapentin had little or no effect on PRV-induced pelvic pain.
These data demonstrate that bladder-associated pelvic pain is attenuated by antagonists of NK1R and H2R. Therefore, NK1R and H2Rrepresent direct therapeutic targets for pain in IC/PBS and potentially other chronic pain conditions.