Neurogenic inflammation

Let me propose that propecia causes a deprivation of hormones needed to maintain the healthy vasculature and nerves in the prostate. When the prostate is shrunk these are damaged to a degree and neuroendocrine homeostasis is lost. This is exacerbated when DHT surges back in. This leads to neurogenic inflammation where substance p and CGRP cause inflammation in the prostate and to the surrounding regions. This in turn causes stress on the surrounding homeostatic mechanisms disrupting androgen receptors and their function.

springerlink.com/content/v412743317w49632/

These findings raise the possibility that prostatic neuroendocrine peptides (such as substance P) may modulate the response of prostate to androgens.

Read this as well: books.google.co.uk/books?hl=en&lr=&id=S3W3hpfXlDAC&oi=fnd&pg=PA1&dq=Neuroendocrine+cells+and+peptidergic+innervation+in+human+and+rat+prostate.&ots=1_tYaHSsOA&sig=ZwoxL1_MTAa_IMb3adfwivoD6Rw#v=onepage&q&f=false

I do not believe that the problem is an infection in nature and think the benefit from antibiotics is an anti inflammatory one. Only the antibiotics that penetrate the prostate can provide anti inflammatory responses such as tetracyclines and quinolones. I cannot however find literature directly linking substance p and antibiotics together but it is well known antibiotics are anti inflammatory.

Massages reduce pelvic floor tone. (i am concluding this from mendeley.com/research/modified-thiele-massage-therapeutic-intervention-female-patients-interstitial-cystitis-hightone-pelvic-floor-dysfunction/) This in turn MIGHT help reduce the release of this pro-inflammatory substances.

This inflammation then causes our issues and is not relieved by hormonal therapy. In fact it is potentially worsened by testosterone as

deepblue.lib.umich.edu/bitstream/2027.42/29845/1/0000192.pdf.

Thus, testosterone regulates substance P levels in areas that regulate mating behaviour.

Vitamin D as i have previously shown is thought to reduce prostatic inflammation.

ncbi.nlm.nih.gov/pubmed/20398021

Data reviewed here demonstrate that VDR agonists, and notably elocalcitol, reduce the static component of BPH by inhibiting the activity of intraprostatic growth factors downstream of the androgen receptor, the dynamic component by targeting the RhoA/ROCK pathway in prostate and bladder cells, and the inflammatory component by targeting the NF-kappaB pathway.

ncbi.nlm.nih.gov/pubmed/17241782

We have documented the anti-inflammatory effects of BXL-628 also in animal models of autoimmune prostatitis, observing a significant reduction of intra-prostatic cell infiltrate following administration of this VDR agonist, at normocalcemic doses, in mice with already established disease.

jimmunol.org/content/159/10/4952.short

The stimulatory effect of substance P was specific, since an NK-1- selective receptor antagonist completely prevented NF-kappa B activation in response to substance P, but not IL-1 beta. In addition, we show that the activity of substance P required mobilization of intracellular calcium and formation of reactive oxygen intermediates as second messengers. Our results suggest that NF-kappa B may be an important component controlling neurogenic inflammation within the peripheral and central nervous system.

Also it is not a long shot to say psoriasis is thought to be related to substance P and CGRP and vitamin D is being proposed as a treatment for this.

ncbi.nlm.nih.gov/pubmed/21747838

As we know here propecia also can affect the brain. I have not suggested the mechanism for this. It seems however to be a seperate process as some of us have just brain symptoms and others sexual.

Some might argue that this does not explain the androgen resistant appearance some of us have and the crash fully. I accept these as limitations.

However, I personally show no signs of androgen resistance and have perfect hormones including 3 adiol G. I also systemically improved on antibiotics and with vitamin D. I have not improved with hormonal therapy as they only made things worse especially the pain. They did make me lose hair faster, get worse acne etc…

This theory suggests that androgen receptors are not doing what they should due to the neuropeptides that have been released. I agree that it is not strictly resistance to testosterone and DHT though as resistance would lead to increased LH and testosterone as they would try to compensate.

HPTA axis abnormalities are common in patients with prostate related disease. Is it hard to believe there is a knock on effect? Of course one can argue the prostate issues are a knock on effect of something else.

I know personally the only things that have helped me are antibiotics, vitamin D, walking, keeping active and reducing stress. I also feel it is important to note that i had no prostate pain until after antibiotics and i also had no sexual function (still not great) til after antibiotics.

This is one more theory that i think warrants investigation.

I hope i have offered a balanced view.

Hi 19, interesting stuff about neuroendocrine peptides and androgens, I will have to read the book you reference (there seems little doubt if you have a numb penis your nerves are not working).

I am interested in two quotes you made:

Can you show me exactly where there is information showing T or DHT may cause negative effects in this instance?

The statements are speculative based on the idea that if testosterone regulates substance P levels, and substance P levels modulate response to androgens that when a surge of DHT is let back in (which is more potent than testosterone) a potential shift in substance P levels may lead to inflammation and also a change in the manner in which the androgen receptor works.

Also statins may prove helpful:

ncbi.nlm.nih.gov/pubmed/18079356

These findings identify a novel action of statins involving down-regulation of proinflammatory neuropeptide expression in sensory ganglia via cholesterol depletion and decreased Smad1 activation and suggest that statins may be effective in attenuating neurogenic inflammation.

news.bbc.co.uk/1/hi/health/8016006.stm

They found inflammation levels among the samples were 72% lower in men who had been taking statins.

Also i know this may be unrelated but tryingnottoworry improved significantly on a high dolichol diet. Statins reduce dolichol production somewhat as does finasteride. Perhaps there is a link.

You also said this:

Have you any evidence that androgen deprevation may lead to any inflammation in such an instance?? (or ever?)

Or any evidence that inflammation stops androgen receptors working properly?

1 Like

This is a theory Oscar. I am basing it on peoples experiences and the evidence available to us.

People experience prostate inflammation (myself included). I am proposing this neurogenic in nature and caused by things like substance P. Substance P is linked to testosterone. Substance P can alter androgen receptors and the way they work. Testosterone and DHT are influenced by propecia.

Awors study has shown a problem with androgen receptors in people like us.

I am saying it warrants investigation but i feel it is not too wild a hypothesis. If you can add any literature to the discussion that would be most helpful.

I have proposed in the past that androgen deprevation may cause the peripheral nerves in the genitals to become inflammed. I have also proposed that adding DHT may cause those nerves to become further inflammed. Seems reasonable.

But there is no evidence in the literature that either of those two things can happen. (None that I could find anyway, which suggests its very well hidden, or actually contrary to how the body works). Thats why im asking.

…

You need to be a bit clearer if you are actually referencing something new you have found, or just thinking out loud.

This theory is interesting and crosses into some post i made about the marshall protocol and benicar, which is a VDR agonist.

also this falls in line with Dr. Art ayers believing that propecia problems are inflammatory/autoimmune

coolinginflammation.blogspot.com/

Is anyone with prostatic issues on a statin???

May give a statin a short course to see if it has an effect. It does reduce substance P and reduces the chance of prostate cancer.

Statins do not affect hormonal parameters

cebp.aacrjournals.org/content/16/8/1587.short

BUT they do decrease AR protein by proteolysis.

onlinelibrary.wiley.com/doi/10.1002/pros.21243/full

RESULTS
Western blotting revealed that both mevastatin and simvastatin downregulated AR and PSA protein. However, these statins did not downregulate AR mRNA expression, while they decreased PSA mRNA. The protease inhibitor MG132 inhibited the downregulation of AR protein which suggested that statins decreased AR protein levels by increasing AR proteolysis. Furthermore, statins reduced cell proliferation in AR positive cells but not in AR negative cells, suggesting that statins regulate cell proliferation via AR expression. In addition, cell proliferation assay at various concentrations of dihydrotestosterone (DHT) showed that statins decreased androgen sensitivity in LNCaP cells.

CONCLUSIONS
Statins decreased AR protein by proteolysis but not mRNA transcription. The drop in AR levels resulted in a reduction in androgen sensitivity and a decrease in cell proliferation in AR positive prostate cancer cells

So would be interesting to see whether it has an effect on us. Awors theory suggests the original thing that messed us up was androgen hypersensitivity. Perhaps by reducing it “normality” can set in again??

Also I can’t recommend vitamin D enough. It decreases inflammation in the prostate, decreases prostate cancer risk, increases AR transcription and quite a few of us have had benefit on it. I swear it really helped me when on holiday. The question is which one of the above is the most useful.

I can’t get the same effect from vitamin d supplements as the sun. I felt like a greek sex god on holiday.

I imagine thats a dosage issue. You get tons from the sun. Little from most supplements.

statins have side effects of their own. Just keep that in mind

i noticed we share many similar side effects with fibromyalgia - i found this link regarding its treatment. It mentions substance P, inflammation, etc.

fmtlc.com/treatment.html

onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2008.07493.x/full

A bit about neurogenic inflammation.

Interesting but scary. I think this is a good theory.

i agree with that

why just focusing on androgen deprevation?
All the hormones were unbalanced
these publications suggest it is possible, moreover hormonal imbalance are already known to cause issue such as gums inflammation for example.
ncbi.nlm.nih.gov/pubmed/20626154

To construct a rat model of chronic nonbacterial prostatitis We established a CP rat model by estrogen induction

ncbi.nlm.nih.gov/pubmed/17440979

The goal of the present study was to induce prostatic inflammation with estrogen and androgen treatment and to record associated urodynamic changes in Noble rats.
Rats were treated with estradiol and testosterone implants to increase estradiol concentration in serum

it doesn’t seem so but that was hertoghe was saying to solonjk: “if you don’t respond to hormones supplementation you are likely to have somme inflammation” it is not far fetched to imagine that damaged tissues can’t process properly androgens.

19 have a read of this,

viewtopic.php?f=9&t=6119