Since being created by the National Institute of Diabetes and Digestive and Kidney Diseases back in 2007, the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network has continued to study IC more closely in order to design better clinical trials with the goal of identifying helpful treatment for different types of IC patients. The MAPP Research Network is going strong and entering into even more territory to help get answers and help for IC patients.

As a joint effort of urologists throughout the United States and Canada, MAPP researchers continued their work in 2019, publishing 13 articles of findings covering IC, which is also referred to as Urologic Chronic Pelvic Pain Syndrome (UCPPS).

#1 — A study published February of 2019 looked at whether patients who have had UCPPS longer have more severe pain, more urologic symptoms and higher rates of co-morbid conditions. The study looked specifically at the severity of symptoms as well the presence of common co-morbid physical and mental conditions with IC. The researchers analyzed data from the MAPP Research Network. The conclusion was that some males (not females) who had UCPPS for more than two years had more severe symptoms than those with symptoms for less than two years. And no matter their duration of UCPPS, patients were just as likely or unlikely to have co-morbid conditions common to IC. In the end, researchers stated that longer UCPPS symptom duration does not define the risk for patients to have co-morbid conditions.(1)

#2 — In March of 2019, the MAPP Research Network released a summary of insights found throughout the first phase of the MAPP Research Network, which has encompassed more than 1,000 patients. The main findings highlighted in the summary were that patients with UCPPS have structural and functional brain changes. Many patients also have co-morbid conditions of hypersensitivities throughout their bodies. Immune factors are also different in UCPPS patients. Overall, researchers concluded, the findings show that patients with UCPPS have phenotypic abnormalities.(2)

#3 — Near the end of March 2019, MAPP researchers published a study looking at the microbiota (things like bacteria, fungi and viruses) in the urine of female IC patients compared to control participants. Overall, the microbiota were not significantly different between IC patients and the control group. The urinalysis found that IC patients did tend to have more Lactobacillus gasseri and less Corynebacterium in comparison to the control subjects. Researchers said no concrete conclusion could be drawn from this information, but it shows that taking a more comprehensive look at microbiota in the lower urinary tract of IC patients is needed.(3)

#4 — After surveying 24 male and 29 female IC patients, researchers from Washington University published findings in April 2019 about what patients’ perceive as causing their flares and how they treat them. The researchers said that 96.2% of the participants reported having a symptom flare. The patients reported a wide array of reasons for their flares. Some were caused by things widely accepted in the IC community as potentially causing flares such as citrus fruits, alcoholic beverages, caffeine, driving or sitting in various forms of transportation, stress, UTIs and tight clothes. Some less common reasons, which researchers said were previously undocumented, were also reported such as certain foods, hair dye, perfume and toothpaste. As far as treating flares, the most common treatment, with 74.5% of the participants using it, was increasing water intake. Flares were more common in the afternoon or evening as well as among female patients and especially patients with somatic sensory hypersensitivity. The findings can aid in additional studies and research on flare management and prevention, according to the researchers.(4)

#5 — A study published electronically in April 2019 looked at the role of fungi in female IC patients. Researchers collected midstream urine samples from IC patients at the beginning of the study then again at six months and 12 months. Thirteen fungal species were found overall in the samples collected from 202 patients. Patients with more severe symptoms showed a greater fungal diversity as well as an increased presence of Candida. Researchers concluded that their findings suggest that severity of urinary symptoms is associated with the presence of fungi in urine for some IC patients.(5)

#6 — In June of 2019, researchers published findings from a study looking at how pain sensitivity in UCPPS patients compares with healthy counterparts as well as UCPPS patients who had overlapping conditions such as fibromyalgia and irritable bowel syndrome. Using computer-controlled pressure stimuli on the thumbnail bed, which is used to assess the overall body pain threshold, researchers found that patients with UCPPS had an intermediate pain sensitivity. They were less sensitive to the pain than the patients with additional conditions but significantly more sensitive to pain than the healthy control participants. Patients with more severe pain in their pelvis and other body parts had an increased pain sensitivity. Likewise, during flares, pain sensitivity was also increased. Researchers reported that patients who had less pain sensitivity had pain improvement within a year. They concluded these findings suggest pain mechanisms in the central nervous system contribute to UCPPS.(6)

#7 — On June 20, 2019, a study was published looking at the impact early adverse life events have on brain function in patients with UCPPS. The study, which looked at 56 female and 29 male UCPPS patients and 59 female and 27 male health control subjects, used brain scans and data on early adverse life events to assess changes in the brain. The researchers found that early adverse life events seemed to impact the networks of the brains typically associated with pain. Their findings seem to be evidence that early adverse life events increase clinical symptoms and quality of life.(7)

#8 — A study looking at toll-like receptors (TLRs) in IC patients was published July 1, 2019. TLRs are a class of proteins that play an integral role in the body’s immune system. Previous studies have shown these receptors have been activated in other chronic pain conditions, but this hadn’t been well studied in IC patients. Researchers used mice to determine how TLR4 impacts IC patients. They concluded that TLR4 activation plays a substantial role in activating the bladder’s response to what it perceives as harmful stimuli. This could provide an insight into how IC pain works and possibly provide a foundation for new therapies.(8)

#9 — Depressive disorders have been shown to be correlated to atypical corticotropin-releasing factor (CRF) signals, which leads to the release of stress hormones. However, according to researchers in a study published in August 2019, not much is known about CRF regulation. Researchers had previously shown that a deficiency of certain enzymes related to CRF that cause depression mimic IC in mice. This study found that the enzyme acyloxyacyl hydrolase (AOAH) regulates CRF through the aryl hydrocarbon receptor (AhR). Some treatments for depression target AhR. Since IC and depression are being shown to have similar effects, then it’s possible that targeting AhR could work in treating IC.(9)

#10 — In September 2019, MAPP researchers published a study looking at flares in IC patients. They examined flare risk factors, characteristics, intensity and duration in 385 patients in bi-weekly assessments. Of the patients, 24.2% reported no flares, 22.9% reported one flare, 28.3% reported 2-3 flares and 24.6% reported four or more flares, with a maximum of 18 flares during the 11-month period of the study. Pelvic pain and urinary symptoms were significantly worse during flares with the flares lasting for one to 150 days. The researchers found that flares were more common, more symptomatic and/or longer-lasting in women who had worse symptoms in non-flare times, bladder hypersensitivity and/or overlapping chronic pain conditions. They concluded that while flares are common among IC patients, flares vary in frequency and symptoms. The researchers plan to do further studies, in particular on the patients who had more frequent, symptomatic and/or longer-lasting flares.(10)

#11 — For many years both doctors and patients have acknowledged that other chronic conditions tend to be more common among the IC population. Research published in September 2019 took it a step further to examine similarities and differences between patients with pelvic pain and those without pelvic pain but with other chronic pain conditions such as fibromyalgia, chronic fatigue syndrome and irritable bowel syndrome. Of the 1,039 participants, 424 had UCPPS, 200 had non-urologic chronic pain conditions and 415 were healthy control subjects. Unsurprisingly, patients with UCPPS had more urologic symptoms than either of the two groups, but those with non-urologic chronic pain conditions had worse urological symptoms than the healthy controls. Patients with non-urologic chronic pain conditions reported more widespread pain than those with UCPPS. Both groups of patients had increased anxiety, depression, perceived stress and lower levels of extraversion compared to the healthy controls. However, patients with UCPPS and without other chronic pain conditions reported more catastrophizing than their non-urological chronic pain counterparts.(11)

#12 — In November 2019, researchers published a study looking at changes throughout the body during an IC or UCPPS flare. The study started with 60 participants, 55 of whom were able to complete it. Of those who completed the study, 27 were able to provide information based on times of flares and non-flares. Pelvic pain increased significantly during flares for all of the patients. For those patients with other non-urologic chronic pain conditions, pain outside of the pelvis also increased. Understanding how flares impact the entire body based on what conditions a patient has can help with flare management and even flare definitions.(12)

#13 — An additional editorial article was published from the MAPP Research Network in September of 2019 covering flares and lessons learned, but an abstract was unavailable for review.(13)

 

References

  1. Rodriguez B, et. al. Symptom duration in patients with urologic chronic pelvic pain syndrome is not associated with pain severity, nonurologic syndromes and mental health symptoms: a multidisciplinary approach to the study of chronic pelvic pain network study. Urology. Feb 2019 Volume 124.
  2. Clemens JQ, et. al. Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network. Nat Rev Urol. March 2019 Volume 16, No. 3.
  3. Nickel JC, et. al. A culture-independent analysis of the microbiota of female interstitial cystitis/bladder pain syndrome participants in the MAPP Research Network. J Clin Med. March 26, 2019 Volume 8, No. 3.
  4. Lai HH, et. al. Management of Symptom Flares and Patient-reported Flare Triggers in Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS)-Findings From One Site of the MAPP Research Network. Urology. Apr 2019 Volume 126.
  5. Nickel JC, et. al. Urinary fungi associated with urinary symptom severity among women with interstitial cystitis/bladder pain syndrome (IC/BPS). World J. Urol. Feb. 2020, Epub April 26, 2019 Volume 38, No. 2.
  6. Harte SE, et. al. Quantitative assessment of nonpelvic pressure pain sensitivity in urologic chronic pelvic pain syndrome: a MAPP Research Network study. Pain. June 2019 Volume 160, No. 6.
  7. Gupta A, et. al. Impact of early adverse life events and sex on functional brain networks in patients with urological chronic pelvic pain syndrome (UCPPS): A MAPP Research Network study. PLoS One. June 20, 2019 Volume 14, No. 6.
  8. Cui X. Cystitis-induced bladder pain is Toll-like receptor 4 dependent in a transgenic autoimmune cystitis murine model: a MAPP Research Network animal study. Am J Physiol Renal Physiol. July 1, 2019 Volume 317, No. 1.
  9. Aguiniga LM. Acyloxyacyl hydrolase modulates depressive-like behaviors through aryl hydrocarbon receptor. Am J Physiol Regul Integr Comp Physiol. Aug. 1, 2019 Volume 217, No. 2.
  10. Sutcliffe S. A longitudinal analysis of urological chronic pelvic pain syndrome flares in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. BJU Int. Sept. 2019 Volume 124, No.3.
  11. Afari N. A MAPP Network Case-Control Study of Urologic Chronic Pelvic Pain Compared with Non-Urologic Pain Conditions. Clin J Pain. Sept. 26, 2019.
  12. Xu T. Changes in whole body pain intensity and widespreadness during urologic chronic pelvic pain syndrome flares-Findings from one site of the MAPP study. Neurourol Urodyn. Nov. 2019 Volume 38, No. 8.
  13. Kessler TM. Flares of chronic pelvic pain syndrome: lessons learned from the MAPP Research Network. BJU Int. Sept. 2019 Volume 124, No. 3.