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A multipronged inhibition of I\n                    <jats:sub>Na1.7<\/jats:sub>\n                    , I\n                    <jats:sub>Na1.6<\/jats:sub>\n                    , I\n                    <jats:sub>Na1.3<\/jats:sub>\n                    , and I\n                    <jats:sub>Na1.1<\/jats:sub>\n                    \u2014 but not I\n                    <jats:sub>Na1.5<\/jats:sub>\n                    and I\n                    <jats:sub>Na1.8<\/jats:sub>\n                    \u2014 was found for a prototype and named Na\n                    <jats:sub>V<\/jats:sub>\n                    iPA1, which was derived from the Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 intracellular loop 1, and is conserved among the TTXs Na\n                    <jats:sub>V<\/jats:sub>\n                    subtypes. Na\n                    <jats:sub>V<\/jats:sub>\n                    iPA1 expression in primary sensory neurons (PSNs) of dorsal root ganglia (DRG) produced significant inhibition of TTXs I\n                    <jats:sub>Na<\/jats:sub>\n                    but not TTXr I\n                    <jats:sub>Na<\/jats:sub>\n                    . DRG injection of AAV6-encoded Na\n                    <jats:sub>V<\/jats:sub>\n                    iPA1 significantly attenuated evoked and spontaneous pain behaviors in both male and female rats with neuropathic pain induced by tibial nerve injury (TNI). Whole-cell current clamp of the PSNs showed that Na\n                    <jats:sub>V<\/jats:sub>\n                    iPA1 expression normalized PSN excitability in TNI rats, suggesting that Na\n                    <jats:sub>V<\/jats:sub>\n                    iPA1 attenuated pain by reversal of injury-induced neuronal hypersensitivity. IHC revealed efficient Na\n                    <jats:sub>V<\/jats:sub>\n                    iPA1 expression restricted in PSNs and their central and peripheral terminals, indicating PSN-restricted AAV biodistribution. Inhibition of sodium channels by Na\n                    <jats:sub>V<\/jats:sub>\n                    iPA1 was replicated in the human iPSC-derived sensory neurons. These results summate that Na\n                    <jats:sub>V<\/jats:sub>\n                    iPA1 is a promising analgesic lead that, combined with AAV-mediated PSN-specific block of multiple TTXs Na\n                    <jats:sub>V<\/jats:sub>\n                    s, has potential as a peripheral nerve\u2013restricted analgesic therapeutic.\n                  <\/jats:p>","DOI":"10.1172\/jci170813","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T12:00:14Z","timestamp":1715256014000},"source":"Crossref","is-referenced-by-count":20,"title":["Peripherally targeted analgesia via AAV-mediated sensory neuron\u2013specific inhibition of multiple pronociceptive sodium channels"],"prefix":"10.1172","volume":"134","author":[{"given":"Seung Min","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, 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