Pharmacologic attenuation of pelvic pain in a murine model of interstitial cystitis.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These data demonstrate that bladder-associated pelvic pain is attenuated by antagonists of NK1R and H2R. Therefore, NK1R and H2R represent direct therapeutic targets for pain in IC/PBS and potentially other chronic pain conditions.
Rudick
Charles N
CN
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. c-rudick@northwestern.edu
Schaeffer
Anthony J
AJ
Klumpp
David J
DJ
D000818:Animals; D018856:Cystitis, Interstitial / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006633:Histamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D064729:Neurokinin-1 Receptor Antagonists; D017699:Pelvic Pain / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism
D006633:Histamine Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D011968:Receptors, Histamine; D018040:Receptors, Neurokinin-1