{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:34:09Z","timestamp":1764700449348,"version":"3.46.0"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH 5U24DK116214"],"award-info":[{"award-number":["NIH 5U24DK116214"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH NS1R35NS097306"],"award-info":[{"award-number":["NIH NS1R35NS097306"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open Philantropy"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Voltage-gated calcium channels (VGCCs) are multimeric proteins composed of alpha 1, \u03b2 and \u03b3 subunits, as well as one of four auxiliary \u03b12\u03b4 subunits. Although there is considerable preclinical and clinical evidence for a contribution of VGCCs to nociceptive processing, notably the gabapentin-targeted \u03b12\u03b4-1 subunit, unclear is the extent to which other \u03b12\u03b4 subunits contribute to baseline or injury-altered pain and itch processing. Here, we investigated the anatomical and behavioral consequences of deleting \u03b12\u03b4-2, \u03b12\u03b4-3 or \u03b12\u03b4-4 in the mouse and report that selectively ablating each \u03b12\u03b4 subunit leads to different, and in some cases, opposite effects on behavioral indices of pain and itch. Specifically, deleting \u03b12\u03b42 resulted in mechanical and heat hypersensitivity, and an increase in spinal cord microglial immunoreactivity, but reduced scratching (presumptive) itch in response to a pruritogen. In contrast, ablation of \u03b12\u03b43 led to thermal hyposensitivity, but no change in mechanical responsiveness or indices of itch. Mice deficient for \u03b12\u03b44 exhibited hyposensitivity across pain modalities and only minor itch deficits. Interestingly, these differential effects were limited to baseline nociceptive responses, therefore we conclude that the \u03b12\u03b4-2, \u03b12\u03b4-3 and \u03b12\u03b4-4 subunits of VGCCs differentially contribute to pain and itch processing. The mechanisms underlying these differences remain however to be determined.<\/jats:p>","DOI":"10.1371\/journal.pone.0337701","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:23:18Z","timestamp":1764699798000},"page":"e0337701","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential contribution of \u03b12\u03b4 auxiliary subunits of voltage-gated calcium channels in mouse models of pain and itch"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-0735","authenticated-orcid":true,"given":"Joao 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