{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:07:27Z","timestamp":1791551247568,"version":"4.3.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic pain is frequently accompanied by affective disturbances, yet existing analgesics provide limited efficacy and raise substantial safety concerns. The proton-gated ion channel ASIC1a contributes to nociceptive sensitisation and affective pain processing, but the lack of tools that selectively target human ASIC1a has hindered translational progress.<\/jats:p>\n                  <jats:p>Here, we identify a nanobody that selectively recognises human ASIC1a and enhances its endocytosis, thereby reducing surface channel availability and suppressing proton-evoked currents. Using a humanised ASIC1a knock-in mouse model, we combine molecular, electrophysiological, and behavioural approaches to dissect the functional consequences of human ASIC1a modulation in vivo.<\/jats:p>\n                  <jats:p>We show that human ASIC1a expressed in both the anterior cingulate cortex and peripheral nociceptors contributes to inflammatory hypersensitivity and anxiety-like behaviours in chronic pain. Targeted adeno-associated virus-mediated expression of the nanobody in the anterior cingulate cortex, as well as local peripheral delivery of purified nanobody protein, produces analgesic effects accompanied by improvements in affective behaviour.<\/jats:p>\n                  <jats:p>These findings define a trafficking-based mode of human ASIC1a regulation that can be selectively engaged by nanobody binding, supporting nanobody-mediated modulation of human ASIC1a as a translationally tractable strategy for rebalancing the sensory and emotional dimensions of chronic pain.<\/jats:p>","DOI":"10.1093\/brain\/awag316","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:12:45Z","timestamp":1789384365000},"source":"Crossref","is-referenced-by-count":1,"title":["Nanobody-boosted human ASIC1a endocytosis alleviates chronic pain and anxiety-like behaviours"],"prefix":"10.1093","author":[{"given":"Kun","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Anatomy and Physiology, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine , Shanghai 200025 ,","place":["China"]},{"name":"Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200127 ,","place":["China"]},{"name":"Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Renji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200127 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Lei","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine , Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hui","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine , Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine , Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine , Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Yu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine , Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Yi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xinhua Hospital, Institute of Dermatology, Shanghai Jiao Tong University School of Medicine 200092 , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Disease, Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai 201600 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7175-4649","authenticated-orcid":false,"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Kun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Cheng","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai 201600 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Jing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai 201600 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Qun","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine , Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Hua","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai 201600 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1438-0038","authenticated-orcid":false,"given":"Tian-Le","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine , Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2631-0456","authenticated-orcid":false,"given":"Xin","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine , Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,16]]},"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awag316\/71125709\/awag316.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awag316\/71125709\/awag316.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:17:47Z","timestamp":1789575467000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/advance-article\/doi\/10.1093\/brain\/awag316\/8802411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/brain\/awag316","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"article-number":"awag316"}}