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

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.

Post Orgasmic Illness Syndrome (POIS) and Delayed Onset Muscle Soreness (DOMS): Do They Have Anything in Common?

“…It is noteworthy that the role of Piezo2 channels has been demonstrated in premature ejaculation rats, with the involvement of inward currents [18], although we suggest that the mechanism is related to peripheral nerve sensitization and not to TAD-like lesions. Accordingly, premature ejaculation related to mechanical hypersensitivity involves significantly increased Piezo2 in the penis head and in the dorsal root ganglion (DRG) [18] without mechano-energetic lesions.…”

“…It is noteworthy that the role of Piezo2 channels has been demonstrated in premature ejaculation rats, with the involvement of inward currents [18], although we suggest that the mechanism is related to peripheral nerve sensitization and not to TAD-like lesions. Accordingly, premature ejaculation related to mechanical hypersensitivity involves significantly increased Piezo2 in the penis head and in the dorsal root ganglion (DRG) [18] without mechano-energetic lesions. However, in the case of POIS, and underlying DOMS, it is theorized that the Piezo2 channels of the proprioceptive axon terminals of the muscle spindle in the bulbospongiosus and ischiocavernosus muscles suffer an acute stress induced mechano-energetic lesion.…”

“…Furthermore, the acute depletion of spermidine is suggested to be an additional critical mechanism in the pathophysiology of POIS. Another interesting correlation is that many clinicians observed a lifelong premature ejaculation condition among their POIS patients [3,5,6,11] and foresee Piezo2 channels being implicated in the pathomechanism of premature ejaculation [18].…”

Clinical characteristics, allergic response to autologous semen, and desensitization in patients with postorgasmic illness syndrome

“…This may be a result of the Piezo2 channels of the proprioceptive axon terminals of the bulbospongiosus and ischiocavernosus muscle spindles experiencing acute stress-induced mechanoenergetic lesion, 12 as Piezo2 is involved in the pathogenesis of PE. 26 …”

Sensory innervation of the human male prepuce: Meissner's corpuscles predominate

“…To the best of our knowledge, the expression of PIEZO2 in preputial mechanoreceptors has not been investigated. However, Chen et al, ( 2020 ) studied the role of PIEZO2 in the mechanism underlying premature ejaculation in rats and reported that PIEZO2 expression was significantly increased in the penile head and dorsal root ganglia of these rats.…”