Estrous cycle dependent fluctuations of regulatory neuropeptides in the lower urinary tract of female rats upon colon-bladder cross-sensitization

• Published in: PloS one Vol. 9; no. 5; p. e94872
• Main Authors: Pan, Xiao-Qing, Malykhina, Anna P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2014; Public Library of Science (PLoS)
• Subjects: Animals; Biology and Life Sciences; Bladder; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Calcitonin; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - metabolism; Colitis; Colitis - chemically induced; Colitis - metabolism; Colon; Colon - metabolism; Control; Estrogens; Estrous Cycle; Estrus cycle; Female; Fluctuations; Ganglia; Ganglia, Spinal - metabolism; Gene expression; Gonadal Steroid Hormones - pharmacology; Growth factors; Hormones; Inflammation; Inflammatory bowel disease; Intestine; Kinases; Medicine and Health Sciences; Morbidity; Nerve growth factor; Nerve Growth Factors - metabolism; Neurons; Neuropeptides; Neuropeptides - metabolism; Neurosciences; Organs; Pain; Peptides; Peroxidase - metabolism; Physiology; Rats; Research and Analysis Methods; Rodent control; Rodents; Sense organs; Sensory neurons; Sex hormones; Spinal cord; Studies; Substance P; Substance P - metabolism; Urinary bladder; Urinary Bladder - metabolism; Urinary tract; Urogenital system; Urology; Uterus; Vagina; Women's health; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0094872

Co-morbidity of bladder, bowel, and non-specific pelvic pain symptoms is highly prevalent in women. Little evidence is present on modulation of pelvic pain syndromes by sex hormones, therefore, the objective of this study was to clarify the effects of hormonal fluctuations within the estrous cycle on regulatory neuropeptides in female rats using a model of neurogenic bladder dysfunction. The estrous cycle in female rats (Sprague-Dawley, 230-250 g) was assessed by vaginal smears and weight of uterine horns. Neurogenic bladder dysfunction was induced by a single inflammatory insult to the distal colon. Protein expression of calcitonin gene related peptide (CGRP), substance P (SP), nerve growth factor (NGF), and brain derived neurotrophic factor (BDNF) in the pelvic organs, sensory ganglia and lumbosacral spinal cord was compared in rats in proestrus (high estrogen) vs diestrus (low estrogen). Under normal physiological conditions, concentration of SP and CGRP was similar in the distal colon and urinary bladder during all phases of the estrous cycle, however, acute colitis induced a significant up-regulation of CGRP content in the colon (by 63%) and urinary bladder (by 54%, p≤0.05 to control) of rats in proestrus. These changes were accompanied by a significant diminution of CGRP content in L6-S2 DRG after colonic treatment, likely associated with its release in the periphery. In rats with high estrogen at the time of testing (proestrus), experimental colitis caused a significant up-regulation of BDNF colonic content from 26.1±8.5 pg/ml to 83.4±32.5 pg/ml (N = 7, p≤0.05 to control) and also induced similar effects on BDNF in the urinary bladder which was also up-regulated by 5-fold in rats in proestrus (p≤0.05 to respective control). Our results demonstrate estrous cycle dependent fluctuations of regulatory neuropeptides in the lower urinary tract upon colon-bladder cross-sensitization, which may contribute to pain fluctuations in female patients with neurogenic bladder pain.