F hypotheses of underlying mechanisms, primarily because of the wide variation in clinical presentation in these patients. Studies have focused on the contribution of inflammatory mediators and the immune system, for example autoimmunity; urothelial cell structural and function abnormalities, such as maintenance of the bladder barrier function and cellular signaling controlling proliferation, respectively; alterations in pain sensation and voiding due to disruptions in bladder sensory neurons and/ or central nervous system involvement; and establishment of visceral pain resulting from prior microbial infection, such as urinary tract infections (13-18). Many studies of possible disease mechanism have been performed in animal models with features of the clinical condition. A diversity of induced and naturally occurring animal models, primarily rodent and feline, has used to assess neuronal, inflammatory, and infectious processes, among others. While these efforts have certainly provided new insights into relevant GW 4064 site biological events and allowed for in vivo testing of possible therapeutic interventions the relevance of these in vivo findings to human IC/BPS is the subject of long debate (e.g., potential confounders of genetic/strain differences and the absence of key features of the syndrome) (19). Concurrent with attempts at defining biologic aspects, epidemiological studies have addressed IC/BPS definition, impact, course, and risk factors. For example, the Interstitial Cystitis Database (ICDB) Study revealed?Translational Andrology and Urology. All rights reserved.www.amepc.org/tauTransl Androl Urol 2015;4(5):524-Mullins et al. Novel research for interstitial cystitisa greater heterogeneity in patient characteristics than previously thought (20). Both the RICE Study (5,6) and BACH Survey (4,7,21) developed improved case definitions for IC/BPS; more accurate estimates of prevalence; and further characterized symptoms, impact, and risk factors in community-based populations. Importantly, as noted a number of epidemiological studies have shown an association of conditions that share chronic pain as a major symptom with IC/BPS (22-27). A number of large, multi-center clinical study groups, many supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), have examined the efficacy of a wide range of interventions for IC/BPS in placebo/sham controlled clinical trials. These include the Interstitial Cystitis Clinical Trials Group (ICCTG); Interstitial Cystitis Collaborative Research Network (ICCRN); and in light of proposed similarities between IC/BPS and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), the Urologic Pelvic Pain Collaborative Research Network (UPPCRN) [for a more detailed review see (28)]. Of the large number of therapies evaluated by these studies perhaps the most encouraging findings were observed for pelvic floor myofascial physical therapy among women with IC/PBS and pelvic floor tenderness. This intervention resulted in an improvement in an overall symptom measure versus global therapeutic message in a cohort of newly diagnosed IC/PBS (29,30). However, assessments of pain and urologic dysfunction (e.g., urgency and frequency) were not significantly different between CEP-37440MedChemExpress CEP-37440 treatment groups and information on duration of the benefit is lacking, suggesting further studies are needed to define the longer-term clinical benefit and generalizability of this treatment. Although new insights have b.F hypotheses of underlying mechanisms, primarily because of the wide variation in clinical presentation in these patients. Studies have focused on the contribution of inflammatory mediators and the immune system, for example autoimmunity; urothelial cell structural and function abnormalities, such as maintenance of the bladder barrier function and cellular signaling controlling proliferation, respectively; alterations in pain sensation and voiding due to disruptions in bladder sensory neurons and/ or central nervous system involvement; and establishment of visceral pain resulting from prior microbial infection, such as urinary tract infections (13-18). Many studies of possible disease mechanism have been performed in animal models with features of the clinical condition. A diversity of induced and naturally occurring animal models, primarily rodent and feline, has used to assess neuronal, inflammatory, and infectious processes, among others. While these efforts have certainly provided new insights into relevant biological events and allowed for in vivo testing of possible therapeutic interventions the relevance of these in vivo findings to human IC/BPS is the subject of long debate (e.g., potential confounders of genetic/strain differences and the absence of key features of the syndrome) (19). Concurrent with attempts at defining biologic aspects, epidemiological studies have addressed IC/BPS definition, impact, course, and risk factors. For example, the Interstitial Cystitis Database (ICDB) Study revealed?Translational Andrology and Urology. All rights reserved.www.amepc.org/tauTransl Androl Urol 2015;4(5):524-Mullins et al. Novel research for interstitial cystitisa greater heterogeneity in patient characteristics than previously thought (20). Both the RICE Study (5,6) and BACH Survey (4,7,21) developed improved case definitions for IC/BPS; more accurate estimates of prevalence; and further characterized symptoms, impact, and risk factors in community-based populations. Importantly, as noted a number of epidemiological studies have shown an association of conditions that share chronic pain as a major symptom with IC/BPS (22-27). A number of large, multi-center clinical study groups, many supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), have examined the efficacy of a wide range of interventions for IC/BPS in placebo/sham controlled clinical trials. These include the Interstitial Cystitis Clinical Trials Group (ICCTG); Interstitial Cystitis Collaborative Research Network (ICCRN); and in light of proposed similarities between IC/BPS and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), the Urologic Pelvic Pain Collaborative Research Network (UPPCRN) [for a more detailed review see (28)]. Of the large number of therapies evaluated by these studies perhaps the most encouraging findings were observed for pelvic floor myofascial physical therapy among women with IC/PBS and pelvic floor tenderness. This intervention resulted in an improvement in an overall symptom measure versus global therapeutic message in a cohort of newly diagnosed IC/PBS (29,30). However, assessments of pain and urologic dysfunction (e.g., urgency and frequency) were not significantly different between treatment groups and information on duration of the benefit is lacking, suggesting further studies are needed to define the longer-term clinical benefit and generalizability of this treatment. Although new insights have b.
