Antihistamines may play role in treating chronic prostatitis/chronic pelvic pain syndrome
The research team has been using mouse models of autoimmune prostatitis to investigate how mast cells might play a role in pelvic pain and to determine whether inhibitors might be useful treatments. Now, their models suggest these cells also play a role in CP/CPPS—a surprise, since antihistamines aren't a staple of CP/CPPS therapy as they have been in IC.
Moreover, the investigators have turned up evidence of mast cell activation in CP/CPPS patients themselves, as research they presented at the AUA annual meeting in San Francisco showed. They found significantly higher levels of expression of nerve growth factor (NGF) and of mast cell tryptase in the expressed prostatic secretions (EPS) from men with CP/CPPS than they did in EPS from healthy men or men with BPH. That was the team's clue that mast cells play a role in CP/CPPS pain, explained first author Praveen Thumbikat, PhD, a research assistant professor of urology at Northwestern working with Anthony Schaeffer, MD, and colleagues.
The researchers had already developed a mouse model of autoimmune CP/CPPS indicating that mast cells may play a role in this type of chronic pelvic pain. The mice with the induced prostatic autoimmunity demonstrate hypersensitivity to touch in the pelvic region. What's more, the prostates of these mice have significantly higher concentrations of mast cells than those of control mice. And unlike the mast cells in the prostates of control mice, those in the mouse models of CP/CPPS also showed degranulation, demonstrating the cells were activated.
But did that process actually contribute to pain? After inducing prostatic autoimmunity in mice genetically deficient in mature mast cells, those animals showed reduced pain.
Pain appears independent of inflammation
Interestingly, Dr. Thumbikat pointed out, the pain process seems to be independent of inflammation. Both types of mice with induced prostatic autoimmunity showed it, but only the mice with mast cells demonstrated hyperalgesia typical of CP/CPPS, demonstrating that somehow these mast cells play an additional role in producing pain.
"Of course, we took it to the next level and asked the question, 'Can we therapeutically intervene in this system?' " Dr. Thumbikat said.
The team tested three different mast cell inhibitors administered intraperitoneally: the H1 receptor antagonist cetirizine (Zyrtec), the H2 receptor antagonist ranitidine (Zantac), and the mast cell stabilizer cromolyn sodium (Nasalcrom), which is used for allergic rhinitis. Each drug had a small effect, producing about a 20% to 30% reduction in pain, which Dr. Thumbikat called "interesting, but not that significant."
But the combination of the three seemed to have a synergistic effect, he said, producing about a 64% reduction in pain.
Could clinicians successfully treat CP/CPPS empirically with a combination of these medications? Dr. Thumbikat doubts it—at least not without ensuring that patients have a phenotype that would call for the treatment. That phenotype may be a patient with elevated levels of the mast cell activation markers such as NGF and mast cell tryptase.
Further research should be able to indicate whether these are the markers to use and what combination of mast cell inhibitors works best.
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