Hi Muon,
You have some interesting ideas. And it helps that you also have data and case reports from family. I know that you are probably familiar with some of the things I will say in this post, but since some of these topics are highly technical, I will try to over-explain what I am trying to say so that others can follow the discussion.
...What if chronic colonic irritation induces sensitization of afferent nerves to neuropeptides in other parts of the urogenital system?
This might imply that POIS requires (or is caused by) IBS. I think to make this conclusion, we would have to rule out the possibility that the
THING that causes IBS does not also independently cause POIS. In other words distinguish between
correlation and causation.
Could neuropeptides from seminal fluid induce afferent nerve firing in the urinary tract?...
In the recent paper by Alex Strashny, it implies that there are people who only experience POIS from masturbation but not sex and/or nocturnal emission (NE) ("
First assessment of the validity of the only diagnostic criteria for postorgasmic illness syndrome" (Alex Strashny, 2019)). There are other published papers showing POISers that do not experience POIS durning sex even though they ejaculate (see "
Benign coital headache relieved by partner's pregnancies with implications for future treatment" (Selwyn Dexter, 2009)). On this forum also, there are some who self-report that POIS happens more often after masturbation than from sex and NE. Assuming that the neuropeptides in semen do not depend on whether a person has sex, masturbates or has nocturnal emissions, how could these neuropeptides cause POIS in one form of ejaculation and not the other two?
These nerves run all the way up to the brain. The urogenital afferent nerve firing makes the brain signaling back via efferent nerves to unrelated locations...Efferent nerves could release neuropeptides on their turn at these locations
You actually don't need brain-feedback to cause sensation in an unrelated location. There is a phenomenon call
refered pain. An afferent signal in one place can cause an effernent signal in another unrelated location directly.
Refered pain is a phenomenon that is used in ancient medical techniques such as trigger points techniques and acupuncture.
Percutaneous Tibial Nerve Stimulation (PTNS) also works on the same principle.
With that said, note that the afferent/efferent signals pass through the
ganglia neurons of the spinal cord. Ganglia are like "internet routers" for the body. They route signals to-and-from different parts of the body, but also they route signals to-and-from the brain.
The brain cannot tell the difference between a signals coming from the spinal ganglion and signals from afferent/efferent communication. If an S ganglia (at the bottom of the spinal cord) misfires, it can send a signal to the brain that the urogenital track is burning or iching or being touched or feeling pain or pleasure (see below figure: S2, S3, S4). Those feelings can feel real as if there is something happening in the genitals when in fact there is nothing happening to the genitals. Even if there is no inflammation in the genitals, an injured ganglia neuron can make it feel like there is inflammation in the genital location. The same is true for every other organ of the body. All signals to the brain pass through (and are controlled by) the spinal cord ganglion.
S2, S3, S4 If a person has a limb amputated for some reason, they can often still "feel" their missing limb because the spinal ganglia neurons were not removed and are still sending signals to the brain. This is called
phantom limb. Interestingly Dr. Stuart Meloy figured out how to give women orgasms using surgically implanted electrically stimulation of the S2 ganglion (
Dr. Stuart Meloy bio).
Below is a complete map of the C, T, L, and S series ganglion locations (left spinal cord image) and the locations of the body that they influence (right image: sliced front-back).
From my own experience, precum can lead to burning sensations of the the penile urinary tract. I also had problems with a burning sensation of my lower arms in the past. Could these effects both be explained by afferent/efferent nerve firing/release by/of neuropeptides.
How do you rule out norepinephrine (noradrenaline) causing both the release of preejaculate and the burning sensation simultaneously. The some of the adrenergic receptors contract smooth muscle such as in the bladder, seminal vestigal and prostate. This causes pressure to urinate, ejaculate, etc... A norepinephrine release could potentially also cause the burning sensation that you feel. There is still no published paper showing that POISers are sensitive/hypersensitive to semen. 22 percent of Dr. Waldinger's POISers
did not have positive skin prick test. However, there are three published POIS case-studies showing that POISers are not sensitive to semen.
So far, the most successful treatments for POIS in the published literature are diclofenac (80 percent relief, Goldmeier (2010)) and norethisterone (95 percent relief, Dexter (2009)). Both of these treatments produced (same-day) results, were tracked for several months and remained effective throughout (see
POIS literature review). Both papers suggest POIS triggers not involving semen.
...going less crazy who mentioned relieve/disappearance of POIS symptoms when avoiding food triggers... My grandma felt better btw when she did not eat and also had problems with cabbage. My brother gets cognitive dysfunction from food...My brother tested serum serotonin again...and the result is still low...His IL-17 is also decreased.
I recommend taking a look at the ligand table for the
aryl hydrocarbon receptor (AhR). The Indole Metabolites (at the top) are found in cabbage. AhR also inhibits the release of il-17 and il-2.
The difference between primary and secondary poisers might be that the primary ones have an additional genetic mutation leading to intestinal problems.
If you look through the raw data from the last POIS survey (Alex Strashny, La_pet1te_mort) there is no clear age range for when POIS starts. For most genetic disease that I am aware of, there is an age range where the symptoms of the disease start to manifest. But POISers seem to acquire POIS at any stage in life. This makes me skeptical of any strong genetic factor for POIS. But maybe there are weak genetic propensities for POIS.
The cytokokines that are changing in my case are decreasing after orgasm and shoot right back up like IL-10:
https://poiscenter.com/forums/index.php?topic=2891.0
...IL-17, IFN-g and Il-2 also decreases somewhat and shoot back up. I wonder what happens if I measure these neurotransmitter serum levels (serotonin,tryptophan, kynurenine, IDO activity) at a similar time frame...
In
Effects of Sexual Arousal on Lymphocyte Subset Circulation and Cytokine Production in Man (P Haake, U Hartmann, et al., 2004), they showed that in normal people Helper T cells (CD3+CD4+), Suppressor T cells (CD3+CD8+), B cells (CD3-CD20+), IL-6 and TNF-alpha do not change during sex/orgasm. However, they also showed that natural killer cells (NK cells) and other Leukocytes from the innate immune system do increase during sex/orgasm in normal people. It would be really cool if we could reproduce this experiment (measuring all the same parameters) in POISers. We could use the results of the P Haake, U Hartmann, et al. study as a healthy control. This way we know if there is a difference between POISers and non-POISers.
Kruger, et al. showed that serotonin is released during sex/orgasm. So measuring serotonin, tryptophan, kynurenine would be interesting. As long as you have these, you don't need to measure IDO directly. But I also think that measuring
AhR activity (before, 5min after, 1 hour after) will be important for future POIS research since:
--tryptophan and arachidonic acid metabolites stimulate this receptor
--it affects IBD/IBS
--it affects autoimmunity
--it suppresses the innate immune system
Thanks for sharing your insightful ideas. Let me know what you think about this.