Sensory neuron-specific block of multifaceted sodium channels mitigates neuropathic pain behaviors of osteoarthritis. Pain Rep 2025 Aug;10(4):e1288
Date
05/30/2025Pubmed ID
40444021Pubmed Central ID
PMC12119052DOI
10.1097/PR9.0000000000001288Scopus ID
2-s2.0-105006656449 (requires institutional sign-in at Scopus site) 1 CitationAbstract
OBJECTIVE: Multiple voltage-gated sodium channels (NaVs) in the peripheral sensory neurons (PSNs) regulate action potentials and their dysfunction contributes to the pain pathogenesis of osteoarthritis (OA). A combined block of multiple NaV subtypes selectively in the PSNs may, therefore, represent an effective analgesic approach in OA painful neuropathy.
METHODS: To test this hypothesis, we generated recombinant adeno-associated virus (AAV) encoding a potent NaV inhibitory peptide aptamer, termed NaViPA1, that has a multipronged feature of inhibiting tetrodotoxin-sensitive NaV1.7, 1.6, 1.1, and 1.3, characterized in our recent report. Adeno-associated virus-encoded NaViPA1 was delivered into the ipsilateral lumbar 4/5 dorsal root ganglia of rats 2 weeks after induction of knee monoiodoacetate-OA (MIA-OA) and evoked and spontaneous sensory behaviors were followed in 6 weeks.
RESULTS: Expression of NaViPA1 selective in the PSNs produced significant and comparable mitigations of evoked and spontaneous pain behavior and reversal of weight-bearing asymmetry in both male and female MIA-OA rats. Whole-cell current-clamp recordings showed that AAV-mediated NaViPA1 expression normalized action potential firing of the PSNs from MIA animals, suggesting that NaViPA1 attenuated pain behavior by, at least in part, reversing neuronal hyperexcitability.
CONCLUSION: Together, these results support that (1) NaVs in peripheral sensory pathways contribute to MIA-OA pain pathogenesis and (2) NaViPA1 is a promising analgesic lead that, combined with AAV-targeted delivery to pathological sensory ganglia, may be a viable peripherally selective PSN-targeting strategy in mitigating chronic MIA-OA pain behaviors.
Author List
Shin SM, Itson-Zoske B, Xu H, Xiang H, Fan F, Hogan QH, Yu HAuthors
Quinn H. Hogan MD Professor in the Anesthesiology department at Medical College of WisconsinHongwei Yu MD Professor in the Anesthesiology department at Medical College of Wisconsin
