{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T18:00:33Z","timestamp":1773943233394,"version":"3.50.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T00:00:00Z","timestamp":1651363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100008530","name":"FEDER","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia"},{"DOI":"10.13039\/501100006111","name":"Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior","doi-asserted-by":"crossref","award":["PTDC\/MED-NEU\/28623\/2017"],"award-info":[{"award-number":["PTDC\/MED-NEU\/28623\/2017"]}],"id":[{"id":"10.13039\/501100006111","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100020405","name":"Santa Casa da Miseric\u00f3rdia de Lisboa","doi-asserted-by":"crossref","award":["MC-39-2019"],"award-info":[{"award-number":["MC-39-2019"]}],"id":[{"id":"10.13039\/501100020405","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Funda\u00e7\u00e3o Grunenthal, Bolsa de Jovens Investigadores em Dor","award":["SFRH\/BD\/130014\/2017"],"award-info":[{"award-number":["SFRH\/BD\/130014\/2017"]}]},{"name":"Funda\u00e7\u00e3o Grunenthal, Bolsa de Jovens Investigadores em Dor","award":["SFRH\/BPD\/120097\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/120097\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The axon initial segment is a specialized compartment of the proximal axon of CNS neurons where action potentials are initiated. However, it remains unknown whether this domain is assembled in sensory dorsal root ganglion neurons, in which spikes are initiated in the peripheral terminals. Here we investigate whether sensory neurons have an axon initial segment and if it contributes to spontaneous activity in neuropathic pain. Our results demonstrate that myelinated dorsal root ganglion neurons assemble an axon initial segment in the proximal region of their stem axon, enriched in the voltage-gated sodium channels Nav1.1 and Nav1.7. Using correlative immunofluorescence and calcium imaging, we demonstrate that the Nav1.7 channels at the axon initial segment are associated with spontaneous activity. Computer simulations further indicate that the axon initial segment plays a key role in the initiation of spontaneous discharges by lowering their voltage threshold. Finally, using a Cre-based mouse model for time-controlled axon initial segment disassembly, we demonstrate that this compartment is a major source of spontaneous discharges causing mechanical allodynia in neuropathic pain. Thus, an axon initial segment domain is present in sensory neurons and facilitates their spontaneous activity. This study provides a new insight in the cellular mechanisms that cause pathological pain and identifies a new potential target for chronic pain management.<\/jats:p>","DOI":"10.1093\/brain\/awac078","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T20:15:45Z","timestamp":1645560945000},"page":"1632-1640","source":"Crossref","is-referenced-by-count":35,"title":["Sensory neurons have an axon initial segment that initiates spontaneous activity in neuropathic pain"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5864-2215","authenticated-orcid":false,"given":"Ana I.","family":"Nascimento","sequence":"first","affiliation":[{"name":"Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto , 4200-135 Porto, Portugal"},{"name":"Graduate Program in Molecular and Cell Biology, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), University of Porto , 4050-313 Porto, Portugal"}]},{"given":"Tiago F.","family":"Da Silva","sequence":"additional","affiliation":[{"name":"Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto , 4200-135 Porto, Portugal"}]},{"given":"Elisabete C.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Neuronal Networks Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto , 4200-135 Porto, Portugal"}]},{"given":"Liliana L.","family":"Luz","sequence":"additional","affiliation":[{"name":"Neuronal Networks Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto , 4200-135 Porto, Portugal"}]},{"given":"Fernando M.","family":"Mar","sequence":"additional","affiliation":[{"name":"Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto , 4200-135 Porto, Portugal"}]},{"given":"Boris V.","family":"Safronov","sequence":"additional","affiliation":[{"name":"Neuronal Networks Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto , 4200-135 Porto, Portugal"}]},{"given":"Monica M.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto , 4200-135 Porto, 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