Penny Allen

-It's a topic that's taboo for many urologists, but one that needs to be discussed-medical marijuana. 

With marijuana legalized for medical use in Canada since 2001 and now in 17 U.S. states and the District of Columbia, beginning with California in 1996, urology patients in pain have been turning to marijuana for relief. We need to find out if they're getting it. 

Dean Tripp, PhD, associate professor of psychology at Queen's University in Kingston, Ontario, took a first step to do just that by surveying patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) about their use of marijuana and whether it relieved their pain. 

Not surprisingly, the mean pain score was higher in the pain users than in the recreational users (13.47 vs. 12.40 on the NIH Chronic Prostatitis Symptom Index), as was the impact of CP/CPPS on quality of life (8.03 in the pain users vs. 7.16 in recreational users on the Short Form Health Survey). Also not surprisingly, suicidal ideation was higher in the pain users than in the recreational users (0.57 vs. 0.38 on the Patient Health Questionnaire for depression). 

Although the survey did not ask questions about degree of pain relief from or access to traditional pain management medications and techniques, it seems likely that many users of marijuana for pain are those who haven't had adequate relief from prescribed medications or other pain therapies. Marijuana can offer added relief, as a study at San Francisco General Hospital showed. Vaporized cannabis was found to augment the analgesic effects of opioids in chronic pain patients without significantly altering plasma opioid levels (

There were no differences between the pain users and recreational users in the degree of side effects, reasons for stopping, use and frequency, or dose smoked. Among those taking in marijuana in food, pain users tended to use more, with 24% reporting consuming more than 1 gram per dose compared with 9% of recreational users consuming this amount. 

Importantly, the survey asked whether the cannabis was of any benefit in treating or relieving symptoms. 

"At this point in time, with the limited data we have on the matter, the answer for the majority of users is 'yes,' " said Dr. Tripp, who worked on the study with the psychology, urology, and anesthesia departments at Queen's University. 

Of the 58 pain users who answered that question, a sizable majority-67%-said that it did indeed offer pain relief. Very few recreational users answered this question, but of the nine who did, three (33%) said it was beneficial for pain, whereas six (67%) said it wasn't. Compared with many treatments tried in the urologic pelvic pain syndromes, effectiveness in 33% isn't bad, and in 67%, it's remarkable. 

Survey studies including more patients would be needed to confirm that figure. 

Articles

With marijuana legalized for medical use in Canada since 2001 and now in 17 U.S. states and the District of Columbia, urology patients in pain have been turning to marijuana for relief.

Marijuana use prevalent among chronic prostatitis/chronic pelvic pain syndrome patients

-Nearly as many American men as women may suffer from interstitial cystitis/bladder pain syndrome (IC/BPS) symptoms. And more men may have IC/BPS symptoms than have chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) symptoms. These surprising findings from the RAND Interstitial Cystitis Epidemiology (RICE) male study provoked plenty of surprise and controversy at the AUA annual meeting in Atlanta. 

When Dr. Suskind finished her presentation, attendees jumped to the microphone immediately to question the survey methods. One pointed out that nonresponders to a health survey usually have about half the symptoms of responders, so that if two-thirds did not take part in the survey, as Dr. Suskind reported, then the number would be far overestimated. It would be too big a leap from the 149 patients who completed the full interview about symptoms. "Ridiculous," said one urologist about the estimate in a later CP/CPPS session. 

Still, there is survey work to do to confirm whether these numbers indeed reflect the prevalence of IC/BPS in men, Dr. Clemens told 

. In the RICE study of women, IC experts confirmed the IC/BPS diagnosis in a subgroup of women reporting symptoms, helping to confirm the prevalence, but this has yet to be done in the men. 

The prevalence in women based on the RICE data also seemed high when they were first reported, Dr. Clemens pointed out. But further RICE data also showed that most of the women reporting symptoms still had symptoms a year later, that 90% had sought care for these symptoms, and that their quality of life was similar to that of women who have IC diagnosed in the clinic. 

"In men, we don't have that yet because we're just analyzing the data. So, it's possible that this is an overestimate because we may be identifying more mild symptoms, but only time will tell," said Dr. Clemens, associate professor of urology at the University of Michigan. In the women, he pointed out, these methods identify a group that's pretty symptomatic, and although it's not certain that they have IC/BPS, "Whatever they have, you don't want." 

Nearly as many American men as women may suffer from interstitial cystitis/bladder pain syndrome (IC/BPS) symptoms. And more men may have IC/BPS symptoms than have chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) symptoms, new data suggest.

Interstitial cystitis prevalence in men higher than previously thought

-Neurotrophic factors that appear in interstitial cystitis/bladder pain syndrome (IC/BPS) patients' urine and disappear with onabotulinumtoxinA (Botox) treatment point to peptidergic primary bladder afferent nerves as the root of patients' pain and other symptoms. 

What's more, the study presented at the AUA annual meeting in Atlanta confirms a trend in onabotulinumtoxinA treatment of IC/BPS symptoms-injection only in the trigone, the area of the bladder with the most pain-sensing afferent nerves. 

The two neurotrophic factors tested by first author Rui Pinto, MD, and colleagues at Hospital de São João in Porto, Portugal, were brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Both are important in maintaining and supporting bladder sensory nerves, but they are associated with different receptors and respond to distinct neurotrophic factors. BDNF is upregulated and synthesized in response to peripheral inflammation. Increases in nerve growth factor (NGF) are associated with increased expression of BDNF in peptidergic sensory afferents, which are the most common primary bladder afferents, and increases in NGF are also associated with the heightened pain sensitivity associated with neuropathic pain. GDNF is mostly associated with nonpeptidergic C fibers in afferent nerves that primarily innervate the distal urethra. 

The investigators followed patients at 1, 3, and 6 months after treatment, evaluating pain scores on a visual analog scale, a 3-day voiding diary for frequency and nocturia, O'Leary-Sant IC Symptom and Problem Index scores, and International Prostate Symptom Score quality of life scores. 

Before treatment, normalized levels of NGF and BDNF were both significantly higher in the IC/BPS patients than in controls, but GDNF didn't show any significant differences, noted co-author Tiago Lopes, MD. 

One month after treatment, said Dr. Lopes, "We found a significant decrease in NGF and BDNF creatinine ratios and also GDNF creatinine ratio. After 3 months, the values started to increase. At 6 months, the values were more or less like they were at baseline." 

What's more, he said, the change in NGF and BDNF levels tracked the change in pain scores, but there was no such correlation for GDNF. 

				"These data suggest," he concluded, "that neurotrophins are key elements in the pathogenesis of IC/BPS with potential clinical implications."			

Neurotrophic factors that appear in interstitial cystitis/bladder pain syndrome (IC/BPS) patients' urine and disappear with onabotulinumtoxinA (Botox) treatment point to peptidergic primary bladder afferent nerves as the root of patients' pain and other symptoms.

Peptidergic bladder afferent nerves implicated in interstitial cystitis pain

Elements common to many IC/PBS patients' histories point to the potential role of high-tone pelvic floor dysfunction as a symptom generator. These patients often have other lower urinary tract and pelvic organ dysfunction as well as sexual dysfunction that all could be related to pelvic floor musculature. Frequently, pelvic examination does reveal hypertonicity, including pain on palpation of certain "trigger points." And a controlled, randomized study of pelvic floor myofascial therapy showed that the treatment can ease symptoms in some patients. 

Borrowing from MRI measurement techniques used in pelvic organ prolapse, first author A. Lenore Ackerman, MD, and colleagues looked at the records of 15 patients with an IC/PBS diagnosis and MRIs and 15 controls-patients who had MRIs done for fibroids but whose primary symptom was bleeding and not pain. Although not matched one-for-one, the groups were similar in age, parity, age at menarche, gynecologic history, symptom duration, and body-wall adiposity (since body mass index was not usually available). 

In axial sections, the radiologists measured the cross-sectional area of the urethra and the width and length of the levator muscles on the right and the left. They also measured the levator angle formed at the posterior margin of the right and left levators. The rationale for that measurement is that, when the pelvic floor tightens, the posterior border of the levators move anteriorly, thus widening the levator angle. 

Puborectal distance shorter in IC patients 							

 With most of these measurements, differences between the groups were statistically significant. The H lines, or puborectal distance, were significantly shorter in IC/PBS patients. These patients also had significantly shorter levator lengths than controls. The levator tightening may lift the pelvic floor, resulting in the elevation of the vaginal cuff seen in IC/PBS patients, explained Dr. Ackerman, a urology resident at UCLA working with Larissa Rodriguez, MD, and colleagues. What's more, their levator angle was wider, "consistent with the idea that the posterior border of levator moved anteriorly, widening the levator angle," she pointed out. 

The cross-sectional area of the urethra was not significantly different, possibly because of the short urethral length in women. Also, measurements of the M line, an indicator of pelvic organ prolapse, were not significantly different, suggesting "that these findings are due to the changes in pelvic floor and not just to general differences in prolapse between these two groups," said Dr. Ackerman. 

Kenneth M. Peters, MD, chair of urology at Oakland University William Beaumont School of Medicine, Royal Oak, MI, wasn't surprised. 

"I think this puts into perspective what many of us clinically have come to realize," said Dr. Peters, who was not involved with the study. "I'd argue that in 75% of patients I see in my practice who have been told they have IC, it's neuromuscular, it's pelvic floor. And when you treat the pelvic floor, their bowel, their bladder, their urgency/frequency get better." 

				But, he added, you don't need an MRI to see the difference, "You just need to do an exam."			

That helps point to something that urologists can easily do now in their practices to help direct therapy for their IC/PBS patients-do a pelvic exam in which you palpate the levators for hypertonicity and trigger points. Those patients may derive a great deal of benefit from pelvic floor myofascial therapy. 

Whether hypertonicity is the major pain generator in IC/PBS patients rather than some urothelial, immune, or neurologic dysfunction remains to be seen. But if you find it, you can help your patients now. 

For years, some urologists and physical therapists have been saying that the pelvic floor is contracted and shortened because of hypertonicity in patients with interstitial cystitis/painful bladder syndrome (IC/PBS), contributing to their misery. Now, using magnetic resonance imaging measurements, researchers have some physical confirmation that these patients do indeed have a contracted pelvic floor.

Penny Allen

Articles

Marijuana use prevalent among chronic prostatitis/chronic pelvic pain syndrome patients

Interstitial cystitis prevalence in men higher than previously thought

Peptidergic bladder afferent nerves implicated in interstitial cystitis pain

Pelvic floor hypertonicity observed in interstitial cystitis/painful bladder syndrome patients