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.
Original language | English (US) |
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Article number | 2479 |
Journal | Nature communications |
Volume | 14 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2023 |
Funding
This work was supported by the Northwestern University NUSeq Core Facility. The 10x Genomics Chromium System employed for the scRNA-seq is made available with an NIH S10 Grant to NUSeq (1S10OD025120). Thank you to Dr. Dale George for assistance with optimizing the DRG cell preparation for scRNAseq. We thank the study participants and staff of the Rush Alzheimer’s Disease Center. ROSMAP resources can be requested at https://www.radc.rush.edu . We would also like to acknowledge these funding sources: National Institutes of Health grant R01AR077019 (R.E.M.), National Institutes of Health grant R01AR064251 (A.M., R.J.M.), National Institutes of Health grant R01AR060364 (A.M.), National Institutes of Health grant P30AR079206 (A.M.), Rheumatology Research Foundation Innovative Research Award (A.M.), National Institutes of Health grants P30AG10161, P30AG72975, R01AG15819, and R01AG17917 (D.A.B.). This work was supported by the Northwestern University NUSeq Core Facility. The 10x Genomics Chromium System employed for the scRNA-seq is made available with an NIH S10 Grant to NUSeq (1S10OD025120). Thank you to Dr. Dale George for assistance with optimizing the DRG cell preparation for scRNAseq. We thank the study participants and staff of the Rush Alzheimer’s Disease Center. ROSMAP resources can be requested at https://www.radc.rush.edu. We would also like to acknowledge these funding sources: National Institutes of Health grant R01AR077019 (R.E.M.), National Institutes of Health grant R01AR064251 (A.M., R.J.M.), National Institutes of Health grant R01AR060364 (A.M.), National Institutes of Health grant P30AR079206 (A.M.), Rheumatology Research Foundation Innovative Research Award (A.M.), National Institutes of Health grants P30AG10161, P30AG72975, R01AG15819, and R01AG17917 (D.A.B.).
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy