Advances in Urology

In January 2022, Larissa V. Rodríguez, MD, joined NewYork-Presbyterian/Weill Cornell Medical Center as Urologist-in-Chief and Chair of the Department of Urology and the Herbert Fisk Johnson Professor of Reproductive Medicine and Urology at Weill Cornell Medicine. Dr. Rodríguez previously served as Professor of Urology and Obstetrics and Gynecology, Vice Chair of Academics, and Director of the Division of Pelvic Medicine and Reconstructive Surgery at the Keck School of Medicine of the University of Southern California.

Dr. Larissa Rodríguez

An internationally renowned urologic reconstructive surgeon, Dr. Rodríguez specializes in the treatment of women with urinary and pelvic floor conditions, such as pelvic organ prolapse, stress urinary incontinence, genitourinary tract reconstruction, and chronic pelvic pain. A pioneering physician-scientist, Dr. Rodríguez has a broad-based research portfolio extending from the laboratory into the clinic, which continues to be instrumental in advancing the field of pelvic medicine and voiding dysfunction.

Environmental Stress: A Role in Lower Urinary Tract Dysfunction?

As Principal Investigator of the NIH-sponsored Multidisciplinary Approach to the Study of Urologic Pelvic Pain (MAPP) Research Network, Dr. Rodríguez has for the last 12 years been examining the role of environmental stress in the development and maintenance of urinary symptoms, voiding dysfunction, and bladder pain. “We have found that chronic psychological stress and other psychosocial variables can affect urinary function and exacerbate lower urinary tract dysfunction, particularly in patients with overactive bladder or interstitial cystitis-bladder pain syndrome,” says Dr. Rodríguez. She notes that an increasing amount of evidence has highlighted the close relationship between chronic stress and lower urinary tract dysfunction, however, the exact mechanisms underlying it remain unknown.

“Patients have reported that stress led to exacerbations of their urinary tract symptoms,” says Dr. Rodríguez. “Many had a higher prevalence of traumatic events in childhood, anxiety, and stress as a part of their daily lives. In particularly vulnerable individuals, stress and depression can manifest in urinary conditions and what those vulnerabilities are is something we’re trying to figure out. It’s as if the patient’s central nervous system is already primed by that event to predispose them to developing symptoms.”

Finding that stress and psychosocial variables are a significant mediator of the symptoms of lower urinary tract dysfunction has informed and inspired Dr. Rodríguez’s translational research in animal models. Dr. Rodríguez’ MAPP team was the first to use the model of an animal that is predisposed to anxiety to determine if stress generates urinary symptoms, seeking to model what occurs in individuals. Her lab has conducted ongoing studies on the effects of water avoidance stress in a rodent model, research that she will now continue at Weill Cornell Medicine. Since the MAPP studies began exploring the relationship between stress and lower urinary tract dysfunction in animal models, other investigators have looked at benign lower urinary tract conditions that do not have pain, such as patients with overactive bladder whoalso have urinary frequency and urgency.

“Stress, depression, and anxiety seem to be present in individuals suffering from lower urinary tract symptoms at a much higher proportion than the normal population. In the animal, we can try to figure out what is happening at a mechanistic level so that we might be able to identify therapeutic targets and develop new therapies to treat these conditions.” — Dr. Larissa Rodríguez

In the water avoidance stress model, a rodent is placed on a platform centered in the middle of a water-filled basin. The rodent will try to avoid the adverse stimulus (water) by staying on the platform. “This is a very mild stressor,” says Dr. Rodríguez. “We put them on a little pedestal surrounded by water at a normal temperature for an hour each day. Rats can swim, so they could hop off and swim if they wanted to. We discovered that they do develop urinary frequency, bladder pain, and discomfort in other parts of the body from the stress of this experience.”

In a study published in PLOS ONE in 2017, Dr. Rodríguez and her MAPP colleagues presented findings on the effects of water avoidance stress on peripheral and central responses during bladder filling in an animal model, which showed visceral hypersensitivity as well as an increased engagement of portions of the micturition circuit that responds to urgency.

In the March 21, 2022, issue of Frontiers in Physiology, Dr. Rodríguez and a former postdoctoral fellow discussed the application of stress-related animal models as important tools in investigating the effect of chronic stress on lower urinary tract function. They reviewed recent findings and identified stress-related animal models, including the most widely used – water avoidance stress. “The aim of the manuscript was to provide a state-of-the-art overview of stress-related animal models, hoping to obtain mechanistic insights, facilitate model choices, and propose novel treatment strategies for lower urinary tract dysfunction,” says Dr. Rodríguez.

Dr. Rodriquez: Implementing a Broad Mission

As Chair of the Department of Urology at Weill Cornell Medicine, Dr. Rodríguez is emphasizing multidisciplinary collaborations with other departments to enhance the care provided to women and men across the age spectrum for a range of urologic needs, including female pelvic medicine/urogynecology; malignant and benign tumors; kidney, prostate and bladder health; and congenital anomalies. She is also recruiting leading urologists and will cultivate the next generation of urologists through the department’s training programs, with a particular focus on mentorship and diversity.