Piezo2 Mediates a Vicious Cycle of "Mechanical Homeostasis Imbalance-Inflammation" in Sensory Nerves and the Cartilage Endplate - PubMed
3 hours ago
- #low back pain
- #neuroinflammation
- #Piezo2
- Piezo2 mechanosensitive channel plays a central role in discogenic low back pain by mediating a vicious cycle between mechanical imbalance and inflammation.
- Abnormal mechanical stress activates Piezo2 in dorsal root ganglion (DRG) neurons, leading to calcium influx and CGRP release.
- CGRP synergizes with mechanical force to activate the IKKβ/NF-κB pathway via RAMP1 in cartilage endplate (CEP) cells, inducing IL-6 and IL-1β secretion.
- This process further sensitizes DRG neurons, forming a positive feedback loop that drives pain and CEP degeneration.
- Targeted inhibition of Piezo2 (using AAV-shPiezo2 or omega-3 fatty acids) or blockade of CGRP signaling (with Rimegepant) alleviates pain, suppresses inflammation, and delays CEP degeneration in models.