Research challenges traditional models of IC pain

Key Points

Two neuroscientists who research pain mechanisms in PBS/IC and associated conditions have reached similar conclusions: Multimodal therapy, logically pursued, is the best approach for pain management. Ursula Wesselmann, MD, PhD, associate professor of neurology, neurological surgery, and biomedical engineering at Johns Hopkins University School of Medicine, Baltimore, and Karen J. Berkley, PhD, MacKenzie professor of neuroscience, Florida State University, Tallahassee, reviewed neuroscience research and its implications for therapy at the 2006 NIDDK International Symposium: Frontiers in Painful Bladder Syndrome and Interstitial Cystitis.

"The obvious reason to treat pain is that chronic pain significantly impairs quality of life," Dr. Wesselmann said.

In addition, Dr. Wesselmann noted that chronic pain seldom comes alone. She reported that rats sensitized by uterine irritation have an exaggerated response to vaginal irritation, with activation of spinal cord segments well beyond those where the vaginal nerves project. Overlap on the spinal cord from different pelvic visceral organs and somatic areas and this cross-sensitization help explain the several urogynecologic pains that PBS/IC patients have, such as IC and vulvodynia. But neurologic studies show that more than referred pain mechanisms are involved, hence, the high rates of chronic pain outside of referred pain locations, such as headache, chest pain, and joint pain.

Complex response

Pain mechanisms are more complex than once thought, Dr. Berkley observed. The traditional perception of pain sensation is that the gracile nucleus conveys information only about touch, but Dr. Berkley and her colleagues have found that in rats, not only skin stimulation, but also bladder contraction and stimulation of the colon, cervix, and/or vaginal canal can turn them on or off. In addition, the estrus cycle has profound effects on sensitivity to stimulation of the skin and pelvic organs. The response to skin stimulation is greatest when estradiol peaks, and how the neurons respond to stimulation of internal organs varies across the estrus cycle.

In one study, investigators treated the colon or uterine horn of rats with saline as a control or with mustard oil to produce inflammation. They also cut the hypogastric nerve. Inflammation of either the colon or uterus produced extravasation in the untreated bladder in proestrus, but not metestrus. Further, the effects on the bladder were eliminated by hypogastric neurectomy. Although researchers have looked at branching afferents between the two organs as a mechanism of cross-sensitization, Dr. Berkley and her team think most of the mechanisms are central.

Dr. Berkley and her team are looking at the influence on the bladder of endometriosis, which occurs frequently with PBS/IC. They found that experimental endometriosis induces vaginal hyperalgesia, increases visceromotor and pressor responses to vaginal distention, reduces bladder capacity, increases urinary frequency and volume, and increases pain behavior and referred muscle hyperalgesia produced by a ureteral stone. A lesson of this research for PBS/IC, Dr. Berkley said, is that the CNS may be a source of bladder inflammation.