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Signal."],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:p>\n                    Regulator of G protein signaling 4 (RGS4) is a G\u03b1 subunit\u2013interacting protein that modulates the functional responses of various G protein\u2013coupled receptors (GPCRs) and that is present in several components of the nociceptive circuitry. Here, we found that RGS4 in lumbar dorsal root ganglia (DRGs) is required for the maintenance of chronic pain states in mice.\n                    <jats:italic toggle=\"yes\">Rgs4<\/jats:italic>\n                    knockout in\n                    <jats:italic toggle=\"yes\">\n                      Mrgprd\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    nonpeptidergic C-fibers was sufficient to attenuate sensory hypersensitivity in several acute and chronic injury models without affecting acute nociceptive responses. Single-nucleus RNA sequencing in ipsilateral lumbar DRGs from mice with prolonged peripheral nerve injury identified cell subset\u2013specific gene expression changes in\n                    <jats:italic toggle=\"yes\">Rgs4<\/jats:italic>\n                    knockout mice after recovery from mechanical hypersensitivity, including\n                    <jats:italic toggle=\"yes\">Gabbr2<\/jats:italic>\n                    , which encodes the GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptor, in\n                    <jats:italic toggle=\"yes\">Mrgprd<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    fibers. RGS4 competed with G\u03b1\n                    <jats:sub>i<\/jats:sub>\n                    -interacting protein (GINIP) to modulate GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptor signaling, which suppresses neuronal excitability. Analysis of genetically modified mice suggested that imbalances in the interplay between RGS4 and GINIP contribute to the maintenance of sensory hypersensitivity and chronic pain states. Overall, our study reveals critical G protein\u2013modulatory pathways in the DRG that promote the maintenance of sensory hypersensitivity in chronic pain models.\n                  <\/jats:p>","DOI":"10.1126\/scisignal.aed7175","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:58:05Z","timestamp":1791309485000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["The G\u03b1-interacting protein RGS4 in dorsal root ganglia maintains molecular and behavioral maladaptations in murine pain models"],"prefix":"10.1126","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5836-3686","authenticated-orcid":true,"given":"Randal A.","family":"Serafini","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Physiology and Biophysics, Chobanian and Avedisian School of Medicine at Boston University, Boston, MA 02118, USA."},{"name":"Nash Family Department of 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