Touch Fibres, Autonomic Fibres and Kissing
Someone, who regularly emails breaking research that I haven’t spotted or don’t have time to spot, got in touch recently with great insights on an article about Kisspeptin that I had seen. But I had managed to miss several things he spotted that may be important to anyone thinking about PSSD.
A Kiss Before Sex
The article reported a clinical trial on the Effects of Kisspeptin on Libido and Penile Tumescence. It increases libido and penile tumescence.
The problem was it was done in men with Hypoactive Sexual Desire Disorder, which is very different to PSSD.
Another problem was that before this article came out we had been in touch with its key authors Alexander Comninos and Waljit Dhillo from UCL in London and had a long discussion and several emails with them. They were intrigued to hear about PSSD but made it clear that running a trial would need a lot of money and ethics approval and was not going to happen any time soon – unless someone stepped up with the money.
Following the publication my source spotted that one of the authors was David Goldmeier, who has recently retired but was one of the leading experts on PSSD and PGAD and thought it might be worth contacting him.
DG’s view was that Kisspeptin was more likely to help people with an endocrine problem rather than people with a neuropathy and he didn’t think it was likely to halp conditions with a genital neuropathy. It can for instance induce ovulation.
DG’s view on kisspeptin then comes closer to the more endocrine ideas about enduring sexual dysfunction that Roberto Melcangi and his group have been chasing.
David G had another proof of concept suggestion. Get some Kisspeptin and try it out in 5 volunteers. This is the kind of view you are more likely to hear from a medical person than from researchers not used to giving drugs in clinical practice.
So Kisspeptin-54 is synthesized and purified by Bachem (Bachem Holding AG). Sterile vials of kisspeptin-54 were produced by Bachem (Clinalfa; Bachem Distribution Services GmbH). See A Kiss Before Conception. (Great title for an article).
Before rushing into this, it should be noted that Kisspeptin is an injection not a tablet and its not clear how many injections would be needed.
Kisspeptin and the Penis
My researcher colleague spotted other things that escaped me (his ghostwriter) – Kisspeptin genes are not only expressed in the hypothalamus but also in peripheral areas of the body, such as the liver and gonads.
Researching this further he found that blocking the sympathetic nervous system, which is part of the autonomic system, can block the production of Kisspeptin in the ovaries of female rats so that they don’t ovulate.
Perhaps related to this, in males Kisspeptin has been thought to play a part in penile tumescence and the UCL Kisspeptin Trial seems to prove this.
This all fits in with an observation from people with PFS, in particular, and PSSD where people report decreased penile size – a shrinkage. Those who seem to be recovering slowly sometimes report that one of the things they notice is that their penis seems less shrunken.
To my great shame I have been inclined to dismiss this – as I’m sure pretty well all psychiatrists have – as a ‘mental’ problem. This is probably because I like pretty well everyone in training hear about Koro.
The books all firmly say that Koro is a delusional disorder found mostly in Asian men who claim their penis is shrinking and may disappear. The silent response of young medical men in the West is probably mostly – ‘thank God this doesn’t happen over here’,
But have we got Koro completely wrong?
One of the shocking things about PSSD is several people I know of have been told by doctors that their ideas about numb genitals being caused by the drugs they were on are delusional – its a somatic delusion they are told.
In this case the deluded people are the doctors – their patients are entirely sane. Have doctors been deluded about Koro also? Have people with Koro got something in common with people with PFS, PSSD and other neuropathic or endocrine conditions?
Treating PSSD and PFS
How might this fit in with PFS and PSSD? Possibly in a few ways.
If PSSD and PFS are neuropathies, the knock-on effects may lead to endocrine problems. I lean this way rather than saying they are endocrine problems which cause a neuropathy in that hormones are not normally a primary cause of neuropathy. Diabetes can lead to neuropathy but this is from glucose toxicity.
Many people with PSSD, maybe most, figure it is not just a genital neuropathy and they are right to think so. There are problems all around the body – in our skin, in our eyes, and definitely in the autonomic system.
An anticholinergic drug called pirenzepine is currently in clinical trials for diabetic neuropathy – aimed at restoring the sensation lost in the peripheral nerves to our lower legs and feet that leads to abnormally low Small Fibre nerve endings on an ankle biopsy.
Pirenzepine is being applied as a paste to legs, and could be given as drops into eyes where diabetics can be shown to lose nerve endings also. The problem is with PSSD, while it might restore some genital sensation, it likely cannot solve all neuropathic problems because it is not absorbed into the body and therefore won’t get to the autonomic nervous system and correct the POTS like problems people with PSSD or SSRI withdrawal have or whatever it is that has turned off Kisspeptin production and caused the penis to shrink and perhaps libido also.
Perhaps Kisspeptin receptors play a part in the additional sensitivity, the pleasurable sensations, found in genitals compared to others areas of the body.
One of the greatest movies I have seen is The Intouchables – in which a quadriplegic man with no sensation below the neck finds his earlobes become intensely pleasurable.
There is so much we just don’t know – so much to find out – so much we will only learn from listening to the people affected and not dismissing them as deluded.
All of this plays into another point that will be picked up in a following post – that one of the things that could be happening in PSSD is that small fibres are affected but primarily those that mediate affective touch using proteins like Prokineticin – See The Holy Grail and RxISK Research Fund.
If this were the case, the ambiguous results on Small Fibre Biopsies in PSSD might be explained – there could be a low normal density of most Small Fibres but a distinctive set of Small Fibres that mediate affective touch could be missing.
These issues all need exploring.
One avenue opening up for further exploration is Corneal Confocal Microscopy which will be the subject of another post soon. See Sex and Thermal Thresholds and Withdrawal and Small Fibre Neuropathy.
The Kiss Scene in Raiders of the Lost Ark
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Comment from Spruce
Slightly off topic, but I wanted to mention one potential idea I have had, to do with the small fibre neuropathy testing, and PSSD.
As with most PSSD sufferers my genitals are numb, and I feel the skin on a lot of the rest of my body has been affected by this numbness too, but to a seemingly lesser extent (sometimes the scalp on my head feels quite numb, and I feel there has been a general numbing on the skin of most of my body, but the numbness on the rest of my body, feels a milder numbness, compared to the numbness in my genitals).
There is one exception. The skin on my lips is noticeably very sensitive, and doesn’t appear to have been affected by the PSSD numbing effect.
This has led me to an idea. Would it perhaps be useful to ask PSSD sufferers to try and identify if there have been any areas on their body, that doesnt seem to have been affected by the PSSD numbing effect; and that seems to have maintained its pre PSSD sensitivity.
Could we then perhaps take a skin sample from this more sensitive area, and somehow compare and contrast it with a skin sample from the area more strongly affected by the numbness, to look for differences in the function, or density, of the small nerve fibres etc, between these two areas?
Would doing this perhaps not help show the mechanism of how SSRI’s might have affected the small fibres, by comparing the difference between numb areas, with areas seemingly not affected by the numbing effect?
Interesting you should mention that your lips are fine. CT fibres are not found in the lips.
“The so-called C-tactile (CT) fibers also have been associated with body perception and social well-being. These and other observations led to the “CT social touch hypothesis” suggesting that CT afferents are of crucial importance as a mediator in interpersonal touch. CT fibers have been recorded from human skin with exception of glabrous skin (eg, the lip vermilion, soles of the feet, and palms of the hands). However, it is still unknown whether the genital area—covered by glabrous and hairy skin—contains CT fibers.”
https://www.sciencedirect.com/science/article/abs/pii/S1743609517303661#preview-section-references
S
They are not my lips – they belong to Spruce. Thanks for the comment – its intriguing. Anything else that might link PSSD to the social touch hypothesis would be great to get.
The paper you link to suggests CT fibres might play a part in hypoactive sexual desire disorder which is the group the Kisspeptin trial was done in
D
I would like to know sth about genital anesthesia. It is a terminology missconception that I need to have claro.
We are talking about genital numbness all the time lately but what is REALLY genital anesthesia?
I have talked about It with several PSSD sufferers and people have different conceptions about that.
Some people complain of genital anesthesia/ numbness in terms of they cant feel anything there. The sense of temperature, rub, pain iz alteres.
Other people like me complain about not feeling erotic sensations innthe genitals. You dont turn on. You dont have your old sexual pleasure when touching so It makes difficult to orgasm etc …but you still feel your genitals are there and have temperature changes, rub, pain etc normally.
Can you Dr Healy make clear what is genital numbness so??
Thanks
We don’t know the answer to this. People vary in the extent of their numbness – for some its just genitals, for others its their entire groin, for others it may include nipples and other bodily parts. For some it is dense so you can rub chilli paste into genitals and they don’t feel it, others are less affected and some claim they have no numbness but on testing you can show they have.
D
Thanks for the update David. One thing to bear in mind is the importance of Kisspeptin dose. At high doses ‘Kisspeptin-54’ acutely induces testicular degeneration in adult male rats via central mechanisms: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697701/ – not something that sounds very helpful to a man suffering with PSSD.
May i ask if there is any alternative to Pirenzepine exept that is absorbed into the body so it can fully affect pssd?
D
This is a great question. There will be another RxISK post in 2-3 weeks laying out the answer to this – when I say answer I don’t mean something that tells anyone what to do but rather the factors everyone needs to take into account when thinking about what to – what might work and how do we stay safe trying it.
I have just submitted an academic article related to the question you ask. Ideally it needs to get accepted before I say too much. If accepted it will hopefully a bunch of leads for you and others to chase.
D
See the last comment from D and response.
Another researcher, someone with a PFS background, got in touch saying:
I saw your post about kisspeptin. I also became interested in this substance. I found a clinical trial by Dr. Stephanie Seminara who has a special interest in this peptide. I contacted her asking whether I could participate. She let me know the trial is for people with hypogonadotropic hypogonadism so I am not eligible. She has publications about kisspeptin.
I also tried DIY treatment. I ordered kisspeptin from CanLab (in Canada) and bought the other gear for injections. I did a few shots and didn’t feel any results. I didn’t keep up with it for long because I was nervous about injecting gray market products on my own.
I want to address another topic in your post, the shrunken penis associated with PFS. I trust you know that DHT has a crucial role in male genital development. Without it, the genitalia are ambiguous and range from non-functional to slightly functional. Abnormalities include hypospadias and micropenis. (The condition is 5-alpha reductase deficiency. The story of the origin of finasteride might be of interest.)
See https://finasterideinfo.org/finasteride-origin-invention/
Merck preposterously suggested that DHT is not necessary in adult males because males with 5-alpha reductase deficiency were generally healthy as adults. (Lots more to say about this but it’s out of scope here.) It is entirely plausible that DHT is involved in maintaining penile tissue health in adult males. I have done considerable investigation into the sequence of events that could lead to penile abnormalities (which resemble Peyronie’s disease).
This article sets the context: Research review: Alterations to penile and prostatic tissue associated with finasteride and dutasteride treatment. Then this manuscript proposes an etiopathology of the penile injuries.
https://finasterideinfo.org/review-penile-prostatic-alterations-finasteride/
DH (ghostwriter for researchers working on enduring sexual dysfunction).
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I find that what generally makes psychiatrists so arrogant, disrespectful and stubborn is that they lack basic academic criteria and critical standards that almost every other field learns early on. Psychiatrists are taught to be always right, that their methods are a kind of absolute super science and doesn’t need further questioning in it’s applications. Every field learns to analyse and question it’s semantics. Maybe especially fields which work a lot with semantics, like the humanities but also history. Psychology and in tandem psychiatry are some of the most semantics heavy fields of all, yet the fields which are the most authoritarian of all. In effect psychiatrists are commonly manipulative and narcissistic, even by common standards. Because they see themselves outside of any standards but their authority.