Targeting Supramolecular Active Complexes of Nav1.7/Nav1.8 to Relieve Chronic Neuropathic Pain - PubMed
3 hours ago
- #SMACs
- #neuropathic pain
- #therapeutic target
- Nav1.7 and Nav1.8 form supramolecular active complexes (SMACs) with a polygonal lattice structure in DRG neurons of chronic neuropathic pain (NP) models and patients.
- TrkB signaling facilitates Nav1.7/Nav1.8 SMAC formation, and combined blockers of these channels synergistically inhibit action potentials and alleviate NP in mouse models.
- Five cytoskeletal proteins (SPTAN1, DSP, AHNAK, MPZ, PRX) promote SMACs, which amplify sodium currents to increase DRG neuron hyperexcitability.
- Knockdown of the five cytoskeletal proteins prevents action potentials in DRG neurons and eliminates neuropathic pain in mice, suggesting SMACs as a pathological hallmark and therapeutic target.