Institution of Urology, The Second Hospital of Shandong University, Jinan, China.
Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Andrology. 2020 Sep;8(5):1347-1359. doi: 10.1111/andr.12779. Epub 2020 Mar 12.
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.
This study explored the possible neural mechanisms of PIEZO2 action in the mechanisms of premature ejaculation using molecular biology and electrophysiology approaches.
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.
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.
Our data demonstrate PIEZO2 involvement in peripheral nerve sensitization, indicating that pharmacological antagonism of PIEZO2 may be a useful strategy for treating premature ejaculation.
阴茎敏感性是早泄的主要病理机制之一。然而，阴茎周围神经致敏的神经生理机制知之甚少。Piezo 型机械敏感离子通道成分 2（PIEZO2）最近被鉴定为一种机械敏感通道。
本研究通过分子生物学和电生理学方法探讨 PIEZO2 在早泄机制中的作用的可能神经机制。
招募了 170 只雄性大鼠和 85 只雌性大鼠。雌性大鼠通过注射苯甲酸雌二醇和孕酮诱导发情，然后手术去势。随后，通过摄像机六次记录交配行为，每周一次。134 只雄性大鼠的最后三次交配过程被成功记录。根据射精频率值将雄性大鼠分为三组。免疫细胞化学和分子方法以及全细胞膜片钳记录用于显示早泄大鼠和对照组大鼠之间的差异。为了进一步阐明 PIEZO2 在早泄中的作用，我们通过鞘内注射 PIEZO2 反义寡核苷酸构建了 PIEZO2 敲低大鼠模型。
我们发现早泄大鼠阴茎头部和背根神经节（DRG）中的 PIEZO2 明显增加。全细胞膜片钳记录显示，机械刺激在早泄大鼠中诱发的内向电流密度明显高于对照组大鼠，这可以被 PIEZO2 特异性拮抗剂 FM1-43 抑制。PIEZO2 敲低实验表明，机械刺激诱导的内向电流密度在 PIEZO2 敲低大鼠中明显降低，PIEZO2 敲低大鼠的交配频率、射精潜伏期和频率均明显改善。
我们的数据表明 PIEZO2 参与周围神经致敏，表明药理学拮抗 PIEZO2 可能是治疗早泄的一种有用策略。
