A pilot study led by University of Kentucky researchers shows that the gene expression analysis of urine sediment could provide a noninvasive way to analyze interstitial cystitis in some patients.
Interstitial cystitis, also known as bladder pain syndrome, is a debilitating disease of the urinary bladder. The disease can occur with or without bladder ulcers (called Hunner lesions). Interstitial cystitis is a difficult disease to study because animal models are limited, and human patients cannot ethically be subjected to invasive research procedures.
The researchers’ goal was to develop a noninvasive method to analyze the bladder epithelium as objectively and directly as possible. During the study, the researchers used microarray technology to analyze cells shed into the urine as an alternative to bladder biopsies, which require anesthesia and have a small risk of bladder injury.
The results showed that urine cells from patients with Hunner lesions had a distinct gene signature for inflammation, similar to the results from a prior microarray study of bladder biopsies. The study was the first to show this inflammation objectively, but without biopsy, in Hunner lesion patients.
If these preliminary results are validated in future research, they may lead to a noninvasive biomarker for Hunner lesion-interstitial cystitis/bladder pain syndrome, says researcher Eric Blalock, associate professor in the Department of Molecular and Biomedical Pharmacology at the UK College of Medicine.
Interstitial cystitis (IC) is a condition that results in recurring discomfort or pain in the bladder and the surrounding pelvic region. The symptoms vary from case to case and even in the same individual. People may experience mild discomfort, pressure, tenderness, or intense pain in the bladder and pelvic area. Symptoms may include an urgent need to urinate, a frequent need to urinate, or a combination of these symptoms. Pain may change in intensity as the bladder fills with urine or as it empties. Women’s symptoms often get worse during menstruation. They may sometimes experience pain during vaginal intercourse.
Because IC varies so much in symptoms and severity, most researchers believe it is not one, but several diseases. In recent years, scientists have started to use the terms bladder pain syndrome (BPS) or painful bladder syndrome (PBS) to describe cases with painful urinary symptoms that may not meet the strictest definition of IC. The term IC/PBS includes all cases of urinary pain that can’t be attributed to other causes, such as infection or urinary stones. The term interstitial cystitis, or IC, is used alone when describing cases that meet all of the IC criteria established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
“A crucial next step will be to determine the stability of this set of biomarkers across larger samples of the population,” Blalock said. “And to also see if similar procedures could be used for early diagnosis and intervention in the disease process.”
For the treatment of moderate pain or moderately severe pain including arthralgia, headache, myalgia, dental pain following oral surgery such as extraction of impacted molars or chronic conditions such as low-back pain, bone pain and cancer-related pain.
- Adults: 100 mg/dose PO or 400 mg/day PO.
- Elderly >= 75 years: 100 mg/dose PO or 300 mg/day PO.
- Elderly 65 – 74 years: 100 mg/dose PO or 400 mg/day PO.
- Adolescents >= 16 years: 100 mg/dose PO or 400 mg/day PO.
- Adolescents 13 – 15 years: Maximum dosage has not been determined.
- Children: Maximum dosage has not been determined.
For interstitial cystitis patients without Hunner lesions, the gene signatures were similar to healthy controls.
What causes IC/PBS?
Some of the symptoms of IC/PBS resemble those of bacterial infection, but medical tests reveal no organisms in the urine of people with IC/PBS. Furthermore, people with IC/PBS do not respond to antibiotic therapy. Researchers are working to understand the causes of IC/PBS and to find effective treatments.
Many women with IC/PBS have other conditions such as irritable bowel syndrome and fibromyalgia. Scientists believe IC/PBS may be a bladder manifestation of a more general condition that causes inflammation in various organs and parts of the body.
Researchers are beginning to explore the possibility that heredity may play a part in some forms of IC. In a few cases, IC has affected a mother and a daughter or two sisters, but it does not commonly run in families.
“This is important in view of the ongoing debate whether the two types of interstitial cystitis really are different disorders,” said UK urologist Deborah Erickson. “Prior studies showed the two patient types did have different findings on bladder biopsies. Our findings support the difference, but without the need for biopsy.”
PAINFUL BLADDER SYMPTOMS
The symptoms of PBS/IC can vary from one person to another and from one episode to another. All patients with PBS/IC have bladder pain that is relieved at least partially by urinating. Symptoms usually include a frequent and urgent need to urinate during the day and/or night. Most, although not all, people with PBS/IC do not have urinary leakage (incontinence). Most people describe pain in the suprapubic area (in the lower abdomen, above the pubic bone) or urethral area. Some people describe one-sided lower abdominal pain or low back pain. The severity of pain ranges from mild burning to severe and debilitating pelvic pain.
Most people describe symptoms that begin gradually, with worsening discomfort, urgency, and frequency over a period of months. A smaller subset of patients describes symptoms that are severe from the beginning. When symptoms of PBS/IC begin suddenly, some patients are able to name the exact date on which symptoms began.
Some people have chronic pelvic pain that is distinct from bladder pain, sometimes with other pain symptoms. Some people have several pain-related diagnoses, such as irritable bowel syndrome, painful menstrual periods, endometriosis, vulvar pain (vulvodynia), or fibromyalgia. PBS/IC symptoms are sometimes at their worst during times when other pain symptoms are also at their worst.
Symptoms may vary from one day to the next. Worsening of PBS/IC symptoms may occur after consuming certain foods or drinks (eg, strawberries, oranges, beer, coffee), or during the luteal phase of the menstrual cycle (14 to 28 days after the first day of the last period), during stressful times, or after activities such as exercise, sexual intercourse, or being seated for long periods of time (eg, during a plane trip).
A person with severe disease may have to urinate several times per hour, which can seriously disrupt daily activities and sleep. As a result of these symptoms, home and work life are often disrupted, interest in sex may be minimal, and the person may have difficulty coping with chronic pain and fatigue. In surveys, 50 percent of patients reported being unable to work full-time, 75 percent described pain with intercourse, 70 percent reported sleep disturbance, and 90 percent reported that PBS/IC affected their daily activities.
The study was published in the February issue of the Journal of Urology and was also selected for post-publication in the Faculty of 1000 (F1000), a global peer review group that identifies and evaluates the most important articles in biology and medical research publications. Selection places a researcher’s work in F1000’s library of the top 2 percent of published articles in biology and medicine.
Source: University of Kentucky