Continuing with my comments (others are welcome to join in):
"...an observation that could be explained by patient selection, a lack of clarity over optimal dosing, and the short duration of therapy."
Notice use of "could" rather than "is". Dr Jordan Dimitrakov (JD) et al are making a tentative suggestion here, not a statement of fact. And that's as it should be, because the idea that patient selection on the basis of different etiology (rather than symptoms) will make a huge difference to outcomes is not well supported in the literature. It's an appealing idea, you know, the concept that this difficult-to-treat bunch of men who present with pelvic pain and are seemingly unresponsive to almost all treatments can be transformed into a group that is much easier to treat, if only you can subdivide them according to (as yet unproven) etiological subclasses.
...prostate infection, autoimmunity, or physical trauma."
Past infection is a proven trigger, but this paper confusingly does not make it clear that the infection is an initiator of the condition, not an ongoing, active cause that must be treated with antibiotics. That is either and oversight, an error, or a deliberate and clever attempt to appeal to the doctors who still adhere, at some level, the the archaic ideas of infection that still swirl around the condition, especially doctors who are not up to date with current research. So it could be diplomacy rather than science. However, the other issue I have with this is that it is presented as representing a different underlying mechanism, and that's where I cannot see any evidence. In my view and according to much anecdotal evidence we've all seen in these forums (and it's backed up by an excellent
2011 study by Schaeffer et al), a past infection can start up the typical cycle of CPPS, and does not represent a unique mechanism that would indicate a unique treatment at all.
Autoimmunity? Where's the proof for that? The main researcher pushing this theory, Richard Alexander, could not show statistical difference between CPPS patients and normal men when measuring autoimmune reactions to prostate proteins ("The recognition of prostate specific antigen peptides was not statistically different when comparing cases to normal male blood donors individually" -
abstract) So why even reference autoimmunity as an underlying cause? If this were an autoimmune condition, we should see some real prostate organ damage, but we don't.
Physical trauma: what kind of physical trauma? Where are the studies that prove physical trauma causes CPPS? It's true that we have seen anecdotal cases where people who have lower or lumbar spinal problems also develop chronic pelvic pain syndrome, probably because of nerve crosstalk, and we have seen women who have had spinal injuries, for instance in a car crash, then go on to develop IC, but where are the studies backing the anecdotes? I do think that any insult to the region can set up a neuromuscular guarding response that then may cascade, in genetically and psychologically susceptible individuals, into CPPS (or IC), but the literature is non-existent and I'm basing this on case histories.
I hope members of the forum can now see some of the problems with the paper (it also has strengths; we'll get to them later).
"the pain might result either from a decreased pain threshold of the peripheral sensory nerve endings or from amplification of the pain perception within the central nervous system (CNS), known as central sensitization"
And here, for me, is one of the paper's strengths. I think this "underlying mechanism" is a factor in
all cases. It's an unmeasurable quantum (I stand open to correction on this) as far as I know, so nobody can say for sure that it's only a factor in
some cases. Without the ability to make that distinction, and using
Occam's Razor, I say it is a factor in
all cases.
In fairness, JD does propose a way to measure this aspect later in the paper: the Lidocaine Test as used in PBS/IC patients. This test would utilize a lidocaine cream to numb the urethra and the urethral part of the prostate. He says "Persistence of pain (negative outcome) would suggest a central pain syndrome." (I need to note that we had a patient of JD's, who had a cream inserted in his urethra,
report that he was permanently affected by the procedure in a negative way.) Whether this test would be able to make a distinction between patients with and without CNS involvement is moot. It's an interesting idea, that's all, at this stage.
However, I like the way this paper brings the CNS factor into the fore. The UPOINT system (
PDF of study) also mentions this factor:
...central and peripheral neurologic changes (allodynia, hyperalgesia), and psychosocial changes that can maintain the clinical syndrome years after the initiating injury has resolved.
The abovementioned quote was cited by Shoskes to the
Pontari study that concluded that CPPS results "from an interplay between psychological factors and dysfunction in the immune, neurological and endocrine systems", which with I'd agree, although I'd add "neuromuscular" to that definition.
"Although the causative factors and pathogenetic mechanisms underlying the symptom (pain) in these two patients are quite different"
I don't think that's been proved at all, and I have to disagree with it.
General comment: these PHENOTYPING systems, (UPOINT and now DABBEC) have arisen because researchers have found no biomarkers to help guide classification and treatment for the condition. But the attempt to phenotype patients is clearly fraught with pitfalls and problems.
At this stage, I think phenotyping systems may be useful in choosing treatments, but not at identifying underlying mechanisms. So yes, by all means classify patients according to symptoms and treat different symptom clusters differently, but do not make the leap to linking symptoms with hypothetical etiology. An example of how classification should be used is given by Shoskes in his paper
CPPS: The Status Quo Is Not Good Enough (But It Can Be)
D Shoskes wrote:Learn and use simple and effective therapies for the
different clinical domains:
• Urinary symptoms: alpha blockers or antimuscarinics
• Prostate pain or inflammation: quercetin and
cernilton
• Systemic neurologic symptoms: pregabalin or
amitriptyline
• Pelvic floor spasm: pelvic floor physical therapy
(myofascial release, NOT Kegel’s)