Piezo1 mediates mechanical signals in TRPV1-positive nociceptors in mice.

Autor: Lee PR; Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea., Ha T; Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.; Department of Life Sciences, Korea University, Seoul, Republic of Korea., Choi HS; Research Animal Resource Center, KIST, Seoul, Republic of Korea., Lee SE; Research Animal Resource Center, KIST, Seoul, Republic of Korea., Kim C; Department of Life Sciences, Korea University, Seoul, Republic of Korea., Hong GS; Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.; Department of Life Sciences, Korea University, Seoul, Republic of Korea.; Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology, Seoul, Republic of Korea.; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
Jazyk: angličtina
Zdroj: Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2024 Nov; Vol. 240 (11), pp. e14236. Date of Electronic Publication: 2024 Sep 26.
DOI: 10.1111/apha.14236
Abstrakt: Aim: This investigation addresses Piezo1's expression and mechanistic role in dorsal root ganglion (DRG) neurons and delineates its participation in mechanical and inflammatory pain modulation.
Methods: We analyzed Piezo1's expression patterns in DRG neurons and utilized Piezo1-specific shRNA to modulate its activity. Electrophysiological assessments of mechanically activated (MA) currents in DRG neurons and behavioral analyses in mouse models of inflammatory pain were conducted to elucidate Piezo1's functional implications. Additionally, we investigated the excitability of TRPV1-expressing DRG neurons, particularly under inflammatory conditions.
Results: Piezo1 was preferentially expressed in DRG neurons co-expressing the TRPV1 nociceptor marker. Knockdown of Piezo1 attenuated intermediately adapting MA currents and lessened tactile pain hypersensitivity in models of inflammatory pain. Additionally, silencing Piezo1 modified the excitability of TRPV1-expressing neurons under inflammatory stress.
Conclusion: Piezo1 emerges as a key mediator in the transmission of mechanical and inflammatory pain, indicating its potential as a novel target for pain management therapies. Our finding not only advances the understanding of nociceptive signaling but also emphasizes the therapeutic potential of modulating Piezo1 in the treatment of pain.
(© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)
Databáze: MEDLINE
Externí odkaz: