Prostatic Diseases and Male Voiding DysfunctionAnimal Models of Urologic Chronic Pelvic Pain Syndromes: Findings From the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network
Section snippets
Quantifying Nociception With the Abdominal Visceromotor Response
IC/BPS patients reported increasing pain with bladder filling.5 In rodents, this was examined with the bladder distention and visceromotor response (VMR) paradigm (described in detail in Fig. 1A,B).6 VMR was used as a surrogate measure of nociception (pain) evoked by bladder distention. During phasic bladder distention, an increase of abdominal VMR or electromyographic signals corresponds to increased guarding and abdominal withdrawal when the animal experiences bladder pain from the
Results
Rodent models were phenotyped during MAPP Research Network studies or prior work with respect to each of the following 3 key factors: (1) nociception to bladder distention, (2) pelvic nociception, and/or (3) urinary frequency, using the methods described previously. Figures 1 and 2 illustrate the methods used to assess nociception and voiding activities and select data from MAPP Network investigators. The overall results are summarized in Table 1. Table 2 describes other features of the models
Comment
Animal models, by definition, cannot perfectly reflect human disease; yet, medical history is replete with mechanistic insights gleaned from animal studies that were otherwise impossible, too invasive, or unethical to obtain from human patients. The shortcomings of animal models of pain, UCPPS in particular, are significant and can undermine the translational value of resulting mechanistic findings if not considered carefully.1, 2, 3 However, models that reflect multiple key characteristics of
Conclusion
The MAPP Network has developed a strategy for evaluating current and future animal models of UCPPS based on human symptomatology. This approach provides a foundation for improved translation between mechanistic studies in animals and clinical research, and serves as a validation strategy for assessing validity of models for symptom-driven disorders of unknown etiology.
Acknowledgment
The authors thank Dr. Philip Hanno (University of Pennsylvania) for the valuable input to the article.
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Financial Disclosure: Financial support was given by the National Institute of Diabetes and Digestive Kidney Diseases MAPP Research Network, grants: DK-082315 (H. Henry Lai, Robert W. Gereau), DK-094964 (H. Henry Lai), DK-082344 (Yi Luo, Michael O'Donnell), DK-082342 (David J. Klumpp). Michel Pontari is a consultant to Eli Lilly Company. The remaining authors declare that they have no relevant financial interests.