Pain: From Basic to Clinic

In this talk, I will present our discovery that Nav1.7, a voltage-gated sodium channel typically known to be specific for sensory neurons, is unexpectedly expressed in non-excitable chondrocytes and plays an important role in the progression of osteoarthritis (OA), as recently published in Nature (Fu, W., et al., Nature, 2024). Serial genetic ablation of Nav1.7 in multiple mouse models demonstrated that Nav1.7 expressed in sensory neurons is involved in pain perception, whereas Nav1.7 expressed in chondrocytes governs OA progression. Additionally, pharmacological blockade of Nav1.7 can simultaneously attenuate the progression of OA and alleviate OA pain. These findings provide a basis for the development of Nav1.7 blockers as novel disease-modifying drugs for treating OA both pathologically and symptomatically, thereby expanding their clinical utility beyond that of painkillers. By elucidating the mechanistic pathways through which Nav1.7 influences chondrocyte biology, we provide novel insights into the role and regulation of sodium channels associated with this debilitating condition.
Additionally, I will briefly highlight our recent review paper (Zhou, R., et al., Nat Rev Rheumatol, 2024), which explores the emerging roles of various ion channels, including sodium channels, in OA. This review emphasizes the therapeutic potential of targeting specific ion channels to manage and treat OA.