This image is from an extraordinary blog which tells you how to sex your mouse
Most of the good ideas that RxISK has featured linked to the enduring sexual dysfunctions, whether PSSD, PRSD, PFS and PGAD, and in terms of other problems, have come from readers of these posts. Several readers have stood out in terms of contributions and this post comes from one of the most helpful contributors.
Hopefully this latest input brings us a big step closer to finding out just what is wrong in PSSD and finding a cure and at some point then the names of all those who have done so much to move this forward can be revealed. They will deserve recognition by scientific and medical bodies.
Once Upon a Time
Back in the 1850s, Wilhelm Krause, an anatomist in Germany described Kraus Corpuscles in male and female genitalia.
Even this is not as simple as it sounds. There were two Wilhelm Krauses – father and son, both anatomists. The first mystery to solve is which Wilhelm described the Corpuscles. Some leads are in the image below from Wilhelm Jrs obituary. My bet is on the father.
A second and more important turn in the plot has come 170 years later when the Corpuscles have exploded back on to the stage with a Qi, Iskols, Handler and Ginty paper revealing that they have a key function in sexual behaviour. Krause Corps respond to vibration and touch and are critical to sexual engagement. Without them nothing happens.
The Qi et al article is above. Here are synopses Thank Your Krause Corpuscles and Mysterious Structures and finally Discovered in the Clitoris and Penis. The final link here comes from New Scientist from someone who has a subscription and I hope that New Scientist and the author Anne Klein will look favourably on the urgent medical need to get this information out there. We will remove it if told to do so.
Back to the Future
This is exciting.
For lots of people, for a long time, it has seemed obvious that PSSD (in all cases where PSSD is mentioned you should also assume PFS, PRSD and PGAD) involves a peripheral neuropathy.
This is obvious in the sense that all things being equal genital numbness means genital neuropathy and not a brain or endocrine problem. You can get the same effect instantly by rubbing local anesthetic into genitals and saying the local nerves have been affected makes more sense than invoking the brain or endocrine system.
Having said that, there is clearly to PSSD in that the effect endures and the enduring aspect may involve other mechanisms.
One thing is for certain – classic pharmacological receptor theory cannot explain either the numbing or the enduring. A lot of bright people have tried out all the drugs that should be tried if this was a matter of reversing or unblocking a receptor. Nothing has helped.
There was great collaboration and trading of information on these issues on early PSSD Forums set up by Antonei Csoka, Audrey Bahrick and others, nearly 20 years ago. This led on to other fruitful hypotheses like Csoka’s epigenetic hypothesis, nearly 15 years old now.
More recently sufferers have turned to tests for peripheral neuropathy as outlined in many RxISK posts stretching back over several years. Some but not all on RxISK pinned their colours to a peripheral neuropathy mast a decade ago. (See Complex Withdrawal Model and PSSD, Withdrawal & Small Fiber Neuropathy?) A group in Finland have been most active in this area lately – see Sensory Receptors, Small Fibres and Neuropathy.
The problem for the Finns, and all the rest of us, is that neurologists have not been interested in peripheral neuropathy and until recently current Tests were pretty crude. They are usually taken around the ankle as this is the area where the peripheral neuropathies neurologists deal with tend to happen. They are taken in older folk and likely test the wrong kind of peripheral nerves to those affected in PSSD. The results have been mixed.
This led RxISK recently to push CCM testing rather than ankle biopsies. CCM looked like having a much better chance of coming up with a positive result than ankle biopsies had.
At the moment only a few people have had CCM testing and at the moment the results do not show the expected signs of something wrong – but this may be because those doing the looking have not had a clear target to look for. Do cornea’s contain Kraus Corpuscles, for instance.
A Dark Horse
Lurking in the background was Quantitative Sensory Threshold Testing (QST), flagged up by the person who has done the most RxISK work on PSSD (not me) nearly a decades ago. (The blog post “How Common is Post-SSRI Sexual Dysfunction?” noted that a form of QST testing had revealed the genital numbing effects of serotonin reuptake inhibitors in 1990 and 1999. This was subsequently highlighted in our published paper, 300 Cases.) Some PSSDers have shown abnormalities on this but it has been impossible to get neurologists to engage – too subjective they have said.
RxISK went to War with a French company who make a gadget that can do QST Testing and who even have a genital adapter to test genitals but they refused to co-operate in making it available despite pleas from me and from several PSSD sufferers. (See Sudoscan Saga & Propecia/Finasteride Survey and Device Wrecks & Regulators?)
It turns out that Krause Corpuscles respond to vibration, temperature and what we call affective touch – just the things QST testing homes in on. See very recent RxISK post on Affective Touch – Sexual Mysteries – asking just this question – are there C-affective touch nerve endings in the penis and genitalia.
If the Krauses are where the problem lies and QST picks it up, this would technically be a peripheral sensory neuropathy, possible a unique one, although the sensory system is so unexplored there may be other sensory neuropathies waiting to be discovered.
We need to find out everything we can about Krause Corpuscles. I have already written to the authors of the Ginty paper but there are likely lots of other folk working on Krause Corpuscles and even checking them on biopsies of genital tissue in people not mice.
We need to check on Krause Corpuscles in the Cornea and around the ankle as they are not found in these locations testing there will just give skeptics ammunition to claim this problem is all in the mind of complainers.
Luisa Guerrini’s work on SSRIs and p63 continues to yield fascinating results that need to be written up and published. In her experimental set-up, thalidomide causes changes that fit with a peripheral neuropathy that recovers once you remove the drug. SSRIs and isotretinoin cause longer lasting changes consistent with an enduring peripheral neuropathy – but of crucial importance they do not do this by causing cell death.
We need to establish the effects of SSRIs, isotretinoin and finasteride on Krause Corpuscles. Are the effects here, if there are any, mediated through mitochondria or is it more a case of treatment leading to enduring problems cutting the Krauses off from their blood supply.
We also need to find treatments that can reverse whatever effects there are – treatments to resurrect the Krauses. This may involve an action on mitochondria – actions on which are hot news at the moment.
In response to a query about Emoxypine from one of our most generous funders a few days ago I wrote:
Had never heard of Emoxypine. It looks similar to, related to Pyridoxal-5-Phosphate – see recent RxISK Post on this. Some people with chronic akathisia have seen it clear up on P5P.
I’ve always thought that genital numbing and emotional numbing are closely related and that drugs that cause these can also cause genital irritability up to PGAD and also cause akathisia which perhaps is the emotional counterpart of genital irritability. So I’ve asked a few people who have reported PGAD to us to try out P5P and let me know what happens.
Here is where things get interesting. There is a good case to be made that as genital nerves pass into the spinal cord that the gateways there shape whether we get genital numbing or irritability and emotional numbing and/or akathisia. In this case P5P might help with PSSD also – but I haven’t asked anyone to try it just yet.
See also the attached article – not sure where it came from – about BC007 and AXA1125. There is something about mitochondria that might be interesting and certainly about getting blood flow going again around peripheral nerve endings.
The main drugs on my radar have been anti-muscarinic drugs which look like they can regenerate nerve endings perhaps by improving blood flow, perhaps through effects on mitochondria.
I think benztropine, in the lowest possible dose taken over several months, is one of the better treatment bets.
(For more about benztropine and PSSD, see The Mysteries of Love.)
Wilhelm or Wilhelm?
This is another mystery that hopefully someone can solve.
Update: some instant super sleuthing has come up with the following.
There is only one Wilhelm – Johann Friedrich Wilhelm Krause 1833-1910. He was the son of “famous anatomist” Karl Friedrich Theodor Krause.
It seems he used a bird embryo to fake human fetal development – see Hopwood – this became a major controversy that might have shed a bad light on his other claims.
The Corpuscles look like they were first described in Die Terminalen Koerperchen. – subtitled The Sensory Nerves. This was published in 1860.