Elsevier

Urology

Volume 85, Issue 6, June 2015, Pages 1454-1465
Urology

Prostatic Diseases and Male Voiding Dysfunction
Animal Models of Urologic Chronic Pelvic Pain Syndromes: Findings From the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network

https://doi.org/10.1016/j.urology.2015.03.007Get rights and content

Objective

To describe the approach taken by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network investigators to advance the utility of urologic chronic pelvic pain syndromes (UCPPS) animal models.

Methods

A multidisciplinary team of investigators representing basic science and clinical expertise defined key phenotypic criteria for rodent models of UCPPS. UCPPS symptoms were prioritized based on their clinical significance. Methods for quantifying animal correlates to patient symptoms were developed. The methods were implemented across proposed rodent models for evaluation and comparison of animals for phenotypic characteristics relevant to human symptomatology.

Results

Pelvic pain and urinary frequency were deemed primary features of human UCPPS and were prioritized for assessment in animals. Nociception was quantified using visceromotor response to bladder distention and by applying von Frey filaments to the lower abdomen (referred tactile allodynia). Micturition activity was assessed as free voiding using micturition cages or blotting pad assays and in response to bladder filling by cystometry. Models varied in both depth of characterization and degree of recapitulating pelvic pain and urinary frequency characteristics of UCPPS.

Conclusion

Rodent models that reflect multiple key characteristics of human UCPPS may be identified and provide enhanced clinical significance to mechanistic studies. We have 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.

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.

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