Piezo2 channels expressed by colon-innervating TRPV1-lineage neurons mediate visceral mechanical hypersensitivity

Xie, Zili; Feng, Jing; Hibberd, Timothy J; Chen, Bao Nan; Zhao, Yue; Zang, Kaikai; Hu, Xueming; Yang, Xingliang; Chen, Lvyi; Brookes, Simon J.; Spencer, Nick J.; Hu, Hongzhen

doi:10.1016/j.neuron.2022.11.015

Cited by 19 publications

(10 citation statements)

References 74 publications

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“…The involvement of Piezo2 in mechanical pain is reported in a number of studies. Most of these studies have examined somatic pain hypersensitivity 11 , 21 , 26 , 28 , 53 , with a recent publication on the role of Piezo2 in TrpV1-lineage neurons in mediation of visceral mechanical hypersensitivity 54 . Since mice with constitutive ablation of Piezo2 from DRG do not survive beyond 24 hours (h) of birth 23 , the approaches of conditional deletion of Piezo2 from subpopulations of DRG neurons have been utilized.…”

Section: Discussionmentioning

confidence: 99%

Piezo2 regulates colonic mechanical sensitivity in a sex specific manner in mice

et al. 2023

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The mechanosensitive ion channel Piezo2 in mucosa and primary afferents transduces colonic mechanical sensation. Here we show that chemogenetic activation or nociceptor-targeted deletion of Piezo2 is sufficient to regulate colonic mechanical sensitivity in a sex dependent manner. Clozapine N-oxide-induced activation of Piezo2;hM3Dq-expressing sensory neurons evokes colonic hypersensitivity in male mice, and causes dyspnea in female mice likely due to effects on lung sensory neurons. Activation of Piezo2-expressing colonic afferent neurons also induces colonic hypersensitivity in male but not female mice. Piezo2 levels in nociceptive neurons are higher in female than in male mice. We also show that Piezo2 conditional deletion from nociceptive neurons increases body weight growth, slows colonic transits, and reduces colonic mechanosensing in female but not male mice. Piezo2 deletion blocks colonic hypersensitivity in male but not female mice. These results suggest that Piezo2 in nociceptive neurons mediates innocuous colonic mechanosensing in female mice and painful sensation in male mice, suggesting a sexual dimorphism of Piezo2 function in the colonic sensory system.

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Section: Discussionmentioning

confidence: 99%

Piezo2 regulates colonic mechanical sensitivity in a sex specific manner in mice

et al. 2023

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“…It has been clearly demonstrated that TRPV1 + DRG but not vagal neurons sense bacterial pathogen–derived signals from Salmonella enterica serovar Typhimurium ( 117 ). Interestingly, a recent study also revealed that PIEZO2 expressed in TRPV1-lineage DRG neurons senses colorectal distension and contributes to subsequently induced physiological and behavioral changes ( 118 ). Cross-organ sensitization has been extensively documented ( 84 ), in particular between the colon and bladder, which are sensed via DRG neurons at the same spinal levels, yet the underlying molecular and cellular mechanisms remain to be determined.…”

Section: Organ-innervating Sensory Neurons Sense Both Primary and Sec...mentioning

confidence: 99%

The Coding Logic of Interoception

Wang,

Chang

2024

Annu. Rev. Physiol.

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Interoception, the ability to precisely and timely sense internal body signals, is critical for life. The interoceptive system monitors a large variety of mechanical, chemical, hormonal, and pathological cues using specialized organ cells, organ innervating neurons, and brain sensory neurons. It is important for maintaining body homeostasis, providing motivational drives, and regulating autonomic, cognitive, and behavioral functions. However, compared to external sensory systems, our knowledge about how diverse body signals are coded at a system level is quite limited. In this review, we focus on the unique features of interoceptive signals and the organization of the interoceptive system, with the goal of better understanding the coding logic of interoception. Expected final online publication date for the Annual Review of Physiology, Volume 86 is February 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…Piezo2 mediates innocuous touch sensation and mechanical hyperalgesia following inflammation and nerve injury ( 111 , 112 ). Piezo2 is also expressed in TRPV1-expressing nociceptors and mediates corneal mechanical pain, visceral mechanical hypersensitivity, and mechanical hyperalgesia in knee joint osteoarthritis ( 113 – 115 ). Therefore, Piezo2 in TRPV1-expressing TG neurons may mediate orthodontic pain; however, this needs to be determined in future studies.…”

Section: Role Of Ion Channels In Periodontal Nociceptors In Orthodont...mentioning

confidence: 99%

Nociceptor mechanisms underlying pain and bone remodeling via orthodontic forces: toward no pain, big gain

Wang,

Ko,

Chung

2024

Front. Pain Res.

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Orthodontic forces are strongly associated with pain, the primary complaint among patients wearing orthodontic braces. Compared to other side effects of orthodontic treatment, orthodontic pain is often overlooked, with limited clinical management. Orthodontic forces lead to inflammatory responses in the periodontium, which triggers bone remodeling and eventually induces tooth movement. Mechanical forces and subsequent inflammation in the periodontium activate and sensitize periodontal nociceptors and produce orthodontic pain. Nociceptive afferents expressing transient receptor potential vanilloid subtype 1 (TRPV1) play central roles in transducing nociceptive signals, leading to transcriptional changes in the trigeminal ganglia. Nociceptive molecules, such as TRPV1, transient receptor potential ankyrin subtype 1, acid-sensing ion channel 3, and the P2X3 receptor, are believed to mediate orthodontic pain. Neuropeptides such as calcitonin gene-related peptides and substance P can also regulate orthodontic pain. While periodontal nociceptors transmit nociceptive signals to the brain, they are also known to modulate alveolar bone remodeling in periodontitis. Therefore, periodontal nociceptors and nociceptive molecules may contribute to the modulation of orthodontic tooth movement, which currently remains undetermined. Future studies are needed to better understand the fundamental mechanisms underlying neuroskeletal interactions in orthodontics to improve orthodontic treatment by developing novel methods to reduce pain and accelerate orthodontic tooth movement—thereby achieving “big gains with no pain” in clinical orthodontics.

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Piezo2 channels expressed by colon-innervating TRPV1-lineage neurons mediate visceral mechanical hypersensitivity

Cited by 19 publications

References 74 publications

Piezo2 regulates colonic mechanical sensitivity in a sex specific manner in mice

Piezo2 regulates colonic mechanical sensitivity in a sex specific manner in mice

The Coding Logic of Interoception

Nociceptor mechanisms underlying pain and bone remodeling via orthodontic forces: toward no pain, big gain

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