Piezo2 expressing nociceptors mediate mechanical sensitization in experimental osteoarthritis

Alia M. Obeidat, Matthew J. Wood, Natalie S. Adamczyk, Shingo Ishihara, Jun Li, Lai Wang, Dongjun Ren, David A. Bennett, Richard J. Miller, Anne-Marie Malfait and Rachel E. Miller ()
Additional contact information
Alia M. Obeidat: Rush University Medical Center
Matthew J. Wood: Rush University Medical Center
Natalie S. Adamczyk: Rush University Medical Center
Shingo Ishihara: Rush University Medical Center
Jun Li: Rush University Medical Center
Lai Wang: Rush University Medical Center
Dongjun Ren: Northwestern University
David A. Bennett: Rush University Medical Center
Richard J. Miller: Northwestern University
Anne-Marie Malfait: Rush University Medical Center
Rachel E. Miller: Rush University Medical Center

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Non-opioid targets are needed for addressing osteoarthritis pain, which is mechanical in nature and associated with daily activities such as walking and climbing stairs. Piezo2 has been implicated in the development of mechanical pain, but the mechanisms by which this occurs remain poorly understood, including the role of nociceptors. Here we show that nociceptor-specific Piezo2 conditional knock-out mice were protected from mechanical sensitization associated with inflammatory joint pain in female mice, joint pain associated with osteoarthritis in male mice, as well as both knee swelling and joint pain associated with repeated intra-articular injection of nerve growth factor in male mice. Single cell RNA sequencing of mouse lumbar dorsal root ganglia and in situ hybridization of mouse and human lumbar dorsal root ganglia revealed that a subset of nociceptors co-express Piezo2 and Ntrk1 (the gene that encodes the nerve growth factor receptor TrkA). These results suggest that nerve growth factor-mediated sensitization of joint nociceptors, which is critical for osteoarthritic pain, is also dependent on Piezo2, and targeting Piezo2 may represent a therapeutic option for osteoarthritis pain control.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38241-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38241-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38241-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().