Areas of Interest

Stress Modulation of Urinary Bladder Pain


Stress is one of the most common human experiences, and stress modifies many other experiences including pain.  It is the rule, rather than the exception that stressful life events, unless coupled with other major physiological events such as pregnancy, lead to an exacerbation of underlying pain disorders.  A prominent role for stress in the pathophysiology and presentation of multiple clinical pain states, including interstitial cystitis/painful bladder syndrome (IC/PBS) has been well documented.  IC is a chronic, debilitating visceral pain syndrome with an incidence of 5-7 in 10,000.  IC is a disease that primarily affects the female population and in its early stages, is characterized by pelvic and/or perineal pain, urinary urgency and frequency, and nocturia.  As the disease progresses, pain increases and becomes the most incapacitating symptom.  Although a number of etiologies have been proposed, the cause of IC is still unclear; however there is clear evidence of a relationship between stress and the exacerbation of bladder pain in functional urinary disorders. 

Recently, our lab has utilized a urological pain model to demonstrate that exposure to experimental stressors magnifies physiological responses to previously innocuous stimuli via a stress-related neuropeptide-mediated mechanism.   There appears to specifically be a role for the CRF2, and its endogenous agonist, Ucn II, in spinal processing of nociceptive information.  We are currently utilizing molecular biology, immunohistochemical, behavioral and electrophysiological techniques to gain a better understanding of stress-induced hyperalgesia in a urological system by dissecting out the role of possible CRF-related neuropeptide modulators of pain sensation.  

 

Intranasal Oxytocin for the Treatment of Pain Associated with Interstitial Cystitis

Anecdotal evidence suggests patients with the painful bladder disorder IC can experience a significant attenuation of their symptoms while breastfeeding.  This observation led to our interest in the effects of the hormones involved in postpartum lactation on stress on nociception.  Using our urological pain model we have demonstrated that lactating rats are less sensitive to urinary bladder distension than controls, chronic stress-induced bladder hypersensitivity was attenuated by oxytocin administered, in the absence of behavioral pretreatment, oxytocin attenuated UBD-evoked responses, and oxytocin-treated rats spent more time in the open arm of an elevated plus maze compared to saline-treated rats.  Based on the results of our experiments, we have hypothesized that the hormone oxytocin has both analgesic and anxiolytic properties which may make it a potentially useful agent for patients with stress-exacerbated chronic pain syndromes such as IC. 

As a result, a clinical trial evaluating the effect of intranasal OXY on pain in individuals with IC has been initiated.  Given the regular use of systemic oxytocin in Obstetrics, there is good safety data related to its use, so the demonstration of analgesic utility could have rapid translation to clinical use.  This study is designed to evaluate whether intranasal oxytocin is effective for pain relief in a cohort of patients with IC.  Novel, non-opioid forms of pain control, especially new medications, are advocated for the use of such chronic pain conditions as IC.  Since intranasal OXY is known to be a relatively safe drug, if our investigations prove efficacy for pain control, this could provide for such an alternative.  It is also possible it could eventually be utilized for other forms of chronic pain as well.