@mesolimbo is there any clue on what causes penile numbness?

[Charm the Snake]

Is it damage to the nerve endings of the glans or more of a deep structure problem that involves hormones?

[stanz92]

It’s definitely deeper than just the nerve endings. When I got my PSSD, I felt sort of like a mini-seizure and my abdomen went numb briefly, and then I lost penile sensation. In fact, it was in a state of paraesthesia for months. I can sense that it goes much deeper than just nerve endings. It’s originates from the brain and is resultant from fundamental damage to the brain somewhere at the back.

[dangerwood]

I don’t believe it is nerve damage because genital numbness is definitely reversible. Myself and many others were able to regain full sensitivity since recovering. I had genital numbness for 2.5 years, now I have no genital numbness and it’s been like that for nearly a year.

[Meso]

It depends on what you mean by genital numbness.

If you can feel touch, friction, pressure and heat sensations but not sexual stimulation, then it's a problem of low or absent libido.

If you can't feel (or much reduced) touch, friction, pressure, and heat sensation, then it's genital numbness.

Antidepressants induce genital numbness by altering:

Antidepressants have recently been found to disrupt transient receptor potential (TRP) channels, inducing genital, and even nipples, numbness. TRPC are are major component of store-operated channels (SOCS). These channels are essential for calcium release in response to neurotransmitter activity. When you blunt these, you end up with impaired sensory nerve function in the periphery, and impaired astrocytes centrally.
https://www.ncbi.nlm.nih.gov/pubmed/25483212
https://www.ncbi.nlm.nih.gov/pubmed/22542657
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598437/

Furthermore, 5HT2B and TRPC4 colocalizes with HTR2B in dorsal root ganglion (or spinal ganglion). As such, reduced 5HT2B activity could potentially induce numbness through further calcium inhibition.
https://www.jacionline.org/article/S009 ... 8/fulltext

[Numby]

It depends on what you mean by genital numbness.If you can feel touch, friction, pressure and heat sensations but not sexual stimulation, then it's a problem of low or absent libido.

If you can't feel (or much reduced) touch, friction, pressure, and heat sensation, then it's genital numbness.

I think it’s more difficult than that. I remember that when I was on fluoxetine I still had very high libido for a couple of days or weeks but I was already numb down there although I could generally feel touch. It’s more like your clitoris or glans turns into non-erogenous tissue. There is a reaction but it’s not a sexual one.

If you touch your forehead or your arm, this can be pleasant and can lead to an erection but you will never reach an orgasm because stimulating your forehead (for example) simply isn’t as intense as stimulating your clitoris or glans.

There are of course people who don’t feel anything at all. But it was different for me.

Edit:
I found this in an article from 2010 called "Pharmacogenetics of SSRIs and Sexual Dysfunction" (by Liana Osis and Jeffrey R. Bishop):

The sexual experience can broadly be divided into three phases.

• Stage 1: interest and desire (libido);

• Stage 2: physiologic arousal; and

• Stage 3: orgasm.

Neurotransmitters and hormones are believed to influence SSRI-associated SD [12,13]. Dopamine, serotonin (5HT), testosterone, and estrogen influence sexual interest and desire (libido). Nitric oxide, acetylcholine, and 5HT are important modulators of physiological sexual arousal. Finally, norepinephrine and 5HT play important roles in orgasm. Recent evidence suggests that additional neurotransmitters such as glutamate may also be involved with sexual physiology [14].

I also found this:

Grafik-StagesOfSexArousal.jpg

This suggests that libido and genital sensitivity are two different issues. I don't know if the article is up to date but penile numbness would then be caused by an imbalance (or so) in nitric oxide, acetylcholine and 5HT. Nothing new, though.

[Meso]

I think it’s more difficult than that. I remember that when I was on fluoxetine I still had very high libido for a couple of days or weeks but I was already numb down there although I could generally feel touch. It’s more like your clitoris or glans turns into non-erogenous tissue. There is a reaction but it’s not a sexual one.

If you touch your forehead or your arm, this can be pleasant and can lead to an erection but you will never reach an orgasm because stimulating your forehead (for example) simply isn’t as intense as stimulating your clitoris or glans.

This is correct, as in the case of antidepressant causing this "erogenous numbness" despite of actually increasing libido in some people. That said, a lot of people here mistake low libido for genital numbness, so I thought I'd clear it up. Some even experience frank numbness (+ nipple numbness).

So, we can agree that there are 3 types of genital numbness: frank mechanical numbness, erogenous numbness, and psuedo-numbness (low libido)

You might be interested in something I wrote in another thread: (I still have to revise and complete it, and write an article on this. But here it is)

1- Genital numbness and the link to pelvic floor dysfunction:
The pudendal nerve is what carries the sensory information from the penis/clitoris (via the dorsal branch) to the cortex of the brain. It also provides motor control of many pelvic muscles (via the inferior rectal nerve -> the perineal nerve). [41]

When this nerve is damaged or impaired, this may lead to sensory loss of the penis/clitoris and/or anal incontinence (inability to control pelvic floor muscles for defecation and urination). In short, this nerve is responsible for sensation in the penis/clitoris and erection, whilst also providing motor control of many pelvic floor muscles responsible for defecation and urination. Such, it functions as both sensory and motor nerve.

Acetylcholine (M2, M3, M4) is the main neurotransmitter of the somatomotor function, with further involvement of glutamate (NMDA), oxytocin, and serotonin (5HT1A).[42][43][44][45][46]

Also, spinal neurons are activated in response to pudendal or nerve stimulation, and carries the signal to the brain. Fast sodium channels are also important for spinal signaling [47]. When acetylcholine neurotransmission is altered, expect impairment of these functions. [48]

Antidepressants have recently been found to disrupt transient receptor potential (TRP) channels, inducing genital, and even nipples, numbness. TRPC are are major component of store-operated channels (SOCS). These channels are essential for calcium release in response to neurotransmitter activity. When you blunt these, you end up with impaired sensory nerve function in the periphery, and impaired astrocytes centrally.
https://www.ncbi.nlm.nih.gov/pubmed/25483212
https://www.ncbi.nlm.nih.gov/pubmed/22542657
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598437/

Furthermore, 5HT2B and TRPC4 colocalizes with HTR2B in dorsal root ganglion (or spinal ganglion). As such, reduced 5HT2B activity could potentially induce numbness through further calcium inhibition.
https://www.jacionline.org/article/S009 ... 8/fulltext

Furthermore, 5HT2B and TRPC4 colocalizes with HTR2B in dorsal root ganglion (or spinal ganglion). As such, reduced 5HT2B activity could potentially induce sensory numbness through further calcium inhibition.
https://www.jacionline.org/article/S009 ... 8/fulltext

Members here often report nipple numbness alongside genital numbness. Nipple oversensitivity is caused by over-expression of TRPV1 in skin nerve fibres and TRPV3 and TRPV4 in keratinocytes.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC554997/

Here's how elevated serotonin induce these symptoms:
- Many antidepressants inhibit both acetylcholinesterase and butyrylcholinesterase activities, this would lead to a compensatory upregulation of these enzymes and reduced central and peripheral cholinergic tone. [49][50]

NOTE: Same thing happens with acetylcholinesterase inhibitors (AChEI). The rapidly reversible actions of donepezil, tacrine and galantamine may lead to tolerance due to their ability to upregulate target enzyme activities; however upregulation is not seen with the slowly reversible (pseudo-irreversible) inhibitor rivastigmine. [51]

- 5-HT1A-mediated suppressing of NMDA receptors signalling via decreasing the number of surface NR2B subunits on dendrites (PFC).
[53][54]

- 5HT-mediated regulation of glutamate release, please refer to my other thread:
http://www.pssdforum.com/viewtopic.php?f=22&t=2754. Long-term elevation of serotonin would blunt glutamate release, and by extension NMDA receptor function.

- Serotonin inhibits voltage gated sodium currents (similar to lidocaine), affecting cortical and spinal nerve conduction. [55] [56] [57]

Treatment of genital numbness:
- Oral capsaicin supplementation. Although chronic activation of TRPV1 causes desensitization, it only happens with topical 8% patch (high concentration). Oral (systemic) intake can actually cause a paradoxical sensitization of TRPV1, and can cause central sensitization via many mechanisms.

- Rivastigmine: It's an acetylcholinesterase inhibitor that doesn't result in tolerance. I've been using Donepezil with success, but a study I have included says it induces tolerance. I will have to switch to Rivastigmine.

NOTE: I advice against Bethanechol since it interferes with spinal pottasium channels and could worsen genital numbness in some cases. [58]

- Cyproheptadine: Or any 5HT2 antagonist/inverse agonist. Since 5HT2 receptors downregulate in response to agonism or antagonism, tolerance should never be a problem. I've tried Cypro, and it had been the best med in combat of low libido and genital numbness, but side effects were intolerable. You may have more luck with a more selective one such as Ketanserin/Flibanserin, with less side effects.

- Drugs or herbs that lower serotonin level: Shilajit, feverfew, SERT activators, etc.

- NMDA potentiation: Sarcosine, D-aspartic acid, etc

[fellow1]

I've reversed numbness with aromasin. And when second time numbness occured, sildenafil reversed it too.

[Tree]

When I crashed from taking ginger, which is a 5ht1a agonist, all symptoms across the board got worse overnight including penile sensation. I literally couldn’t get an erection or feel my dick when it happened. 5ht1a desensitization has a huge influence on sexual and cognitive symptoms of pssd