Sexual touch - (PIEZO2)

[media]

https://www.science.org/doi/full/10.112 ... R58F1yJ-2g

[anacleta]

Thank you. I had become interested in PIEZO2 three years ago and had put together these studies.


Peripheral Mechanobiology of Touch—Studies on Vertebrate Cutaneous Sensory Corpuscles
by Ramón Cobo 1,†,Jorge García-Piqueras 1,†,Yolanda García-Mesa 1,Jorge Feito 2,3,Olivia García-Suárez 1 and Jose A Vega 1,4,*

Int. J. Mol. Sci. 2020, 21(17), 6221; https://doi.org/10.3390/ijms21176221

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Glans clitoris innervation: PIEZO2 and sexual mechanosensitivity
Yolanda García‐Mesa, Lucía Cárcaba , César Coronado , Ramón Cobo
. José Martín‐Cruces , Jorge García‐Piqueras , Jorge Feito . Olivia García‐Suárez , José A. Vega

First published: 29 September 2020 https://doi.org/10.1111/joa.13317

Abstract
The clitoris is a leading player in female sexual arousal, if not the main protagonist. Despite this role, studies performed on this structure with specific neuroanatomical techniques are few. This study focuses on glans clitoris innervation, with special emphasis on sensory corpuscles and the presence of the mechanotransducer protein PIEZO2 in these structures. Six glans clitoris samples were obtained at autopsy covering an age spectrum between 52 and 83 years old. Several types of nerve terminations including free nerve endings, genital endbulbs as well as Meissner‐like corpuscles and Pacinian corpuscles, but not Ruffini corpuscles, were found. Although corpuscular morphology in the glans clitoris was subtly different from the cutaneous digital counterparts, their basic composition was comparable for both Pacinian and Meissner‐like corpuscles. Genital endbulbs showed heterogeneous morphology, and the axons usually exhibited a typical “wool ball” or “yarn ball” aspect. Some of them were lobulated and variably encapsulated by endoneurial elements (65%); from the capsule originate septa that divides the genital endbulbs, suggesting that they are found in clusters rather than as single corpuscles. In addition, most corpuscles in the glans clitoris showed axonal PIEZO2 immunoreactivity, thus, suggesting a mechanical role and molecular mechanisms of mechanosensibility similar to those of digital Meissner's corpuscles. Our results demonstrate that sensory corpuscles of the glans clitoris are similar to those of other glabrous skin zones, as most genital organs are characterized by clusters of corpuscles and the occurrence of the mechanoprotein PIEZO2 in the axons. These findings strongly suggest that PIEZO2 participates in erotic and sexual mechanical sensing.

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The sensory innervation of the human nipple (2020)
https://pubmed.ncbi.nlm.nih.gov/31911160/

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Non-conventional features of peripheral serotonin signalling - the gut and beyond.
Spohn SN1, Mawe GM1

Nature reviews. Gastroenterology & Hepatology, 10 May 2017, 14(7):412-420
DOI: 10.1038/nrgastro.2017.51
http://europepmc.org/article/PMC/5672796


"In addition to 5-HT release in response to surface receptor stimulation, 5-HT release from EC cells [enterochromaffin (EC) cells] can also be activated by mechanical stimulation, and recent evidence indicates that these cells express Peizo2 mechanosensitive ion channels that play an important role in this process. "

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Significance of piezo‐type mechanosensitive ion channel component 2 in premature ejaculation: An animal study
Zhenghao Chen et coll

First published: 26 February 2020

https://doi.org/10.1111/andr.12779

Abstract
Background
Penile hypersensitivity is one of the main pathological mechanisms of premature ejaculation. However, little is known about the neurophysiological mechanism of penile peripheral nerve sensitization. Piezo Type Mechanosensitive Ion Channel Component 2 (PIEZO2), was recently identified as a mechanically sensitive channel.

Objectives
This study explored the possible neural mechanisms of PIEZO2 action in the mechanisms of premature ejaculation using molecular biology and electrophysiology approaches.

Materials and methods
One hundred seventy male rats and 85 female rats were recruited. The females were induced estrus by injection of estradiol benzoate and progesterone followed by surgically castrated. Subsequently, the copulatory behaviors were record by a video camera six times, once a week. The last three mating processes of 134 male rats were successfully recorded. The males were divided into three groups according to ejaculation frequency value. Immunocytochemical and molecular methods as well as whole‐cell patch clamp recording were used to show the difference between premature ejaculation rats and control rats. To further clarify the involvement of PIEZO2 in premature ejaculation, we constructed a PIEZO2 knockdown model in rats by intrathecal injection of PIEZO2 antisense oligodeoxynucleotides.

Results
We showed that PIEZO2 in the penis head and in the dorsal root ganglia(DRG) were significantly increased in premature ejaculation rats. Whole‐cell patch clamp recording demonstrated that mechanical stimulation evoked a higher inward current density in premature ejaculation rats compared with control rats, which could be inhibited by the PIEZO2‐specific antagonist, FM1‐43. PIEZO2 knockdown experiments revealed that the inward current density induced by mechanical stimulation was significantly decreased in PIEZO2 knockdown rats, and that the mount frequency and ejaculation latency and frequency were significantly improved in PIEZO2 knockdown rats.

Discussion and Conclusion
Our data demonstrate PIEZO2 involvement in peripheral nerve sensitization, indicating that pharmacological antagonism of PIEZO2 may be a useful strategy for treating premature ejaculation.

https://onlinelibrary.wiley.com/doi/10.1111/andr.12779


I see that new studies have been published in recent years--to be further investigated.

[anacleta]

Good vibrations
The role of a mechanosensitive ion channel in sexual behavior is unveiled
ARLENE J. GEORGE AND VICTORIA E. ABRAIRA
https://www.science.org/doi/full/10.112 ... ce.adj8674

Lam et al. (1) reveal the necessity of PIEZO2 for sexual touch and copulation in mice and humans. Their results both illustrate how sensory neurons in the genital sub-regions can detect gentle stimuli that promote sexual response, and suggest possible therapeutic targets for sexual dysfunction.

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PIEZO2 and perineal mechanosensation are essential for sexual function
Ruby M Lam et al. Science. 2023.

https://pubmed.ncbi.nlm.nih.gov/37616369/

Using genetic strategies and in vivo functional imaging, we demonstrated that the mechanosensitive ion channel PIEZO2 (piezo-type mechanosensitive ion channel component 2) is necessary for behavioral sensitivity to perineal touch. PIEZO2 function is needed for triggering a touch-evoked erection reflex and successful mating in both male and female mice. Humans with complete loss of PIEZO2 function have genital hyposensitivity and experience no direct pleasure from gentle touch or vibration. Together, our results help explain how perineal mechanoreceptors detect the gentlest of stimuli and trigger physiologically important sexual responses, thus providing a platform for exploring the sensory basis of sexual pleasure and its relationship to affective touch.

[anacleta]

I contacted an author of the latest study on piezo2 and sexual function; he has not yet responded, however,
I passed the study to Melcangi and he replied that PIEZO2 is already under their attention and they are getting data for both finasteride and SSRI
These are long analyses and it takes time, the target is not easy and the literature recent.
Then I think we can confide and support Melcangi's research for this track as well instead of going after others.