Prostate is pain generator in chronic prostatitis/chronic pelvic pain syndrome, model shows

Key Points

Orlando, FL-An animal model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is offering intriguing clues to how pain develops in this syndrome, where it originates, and how to modulate it. Interestingly, the research points back to the prostate as a pain generator at a time when the field has been looking away from the end organ for the pathophysiology of CP/CPPS.

The experimental autoimmune prostatitis model, developed about a decade ago, is based on injecting prostate gland homogenates from rats into diabetic mice. Now researchers at Northwestern University's Feinberg School of Medicine in Chicago are looking at prostate histopathology, the development of pelvic pain, and potential CP/CPPS therapies in this model.

Once prostate autoimmunity was induced in these mice, inflammatory cells gradually infiltrated the prostate, producing focal, periglandular inflammation, eventually resulting in striking change in all three prostate lobes, unlike in control animals, explained first author Praveen Thumbikat, PhD, research assistant professor in the department of urology at Northwestern.

The investigators tested the animals' responses to touch with Von Frey filaments, which have graded stiffness and are used to test tactile sensitivity in conditions such as peripheral neuropathy. In the experimental animals, the investigators noted increased sensitivity of the pelvic region, but no change in response to touch on the footpad, leading the study team to conclude that the mice had developed allodynia, which is sometimes indicative of chronic pelvic pain.

Histologically, the team saw a dramatic increase in neuritic density in the dorsolateral prostate.

"This neuritic density suggests active neuropathic mechanisms underlie pain in experimental autoimmune prostatitis," Dr. Thumbikat explained.

To assess whether other organs were involved, researchers treated the colon, bladder, and prostate of the autoimmune prostatitis mice with lidocaine. Injection of lidocaine into the prostate reduced pain responses by 46%, but treatment of the bladder and colon made no difference, a finding that seems to run contrary to the evidence of neural "crosstalk" among pelvic organs in chronic pelvic pain conditions.

In addition, the investigators gave the experimental animals a systemic neuromodulator, gabapentin (Neurontin), used for neuropathic pain conditions. Within 1 hour, pain responses went down significantly-30%-indicating a central neuropathic pain mechanism may also be at work, Dr. Thumbikat said.

Local anesthesia and neuropathic pain medications have already found a place in CP/CPPS therapy, although an evidence base for neuropathic drugs is still to come because the trial of pregabalin (Lyrica) in CP/CPPS is complete and results are being analyzed.

"There are a lot of patients with symptoms who don't have inflammation," John Krieger, MD, University of Washington, Seattle, noted. In fact, he said, an estimated 70% of men with CP/CPPS do not have inflammation; conversely, many men whose prostates are resected and examined show inflammation without CP/CPPS symptoms.