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Here, we identify GPR35 as a modulator of Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9 function in dorsal root ganglion (DRG) neurons, establishing a previously unrecognized receptor\u2013channel signalling axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Transcriptomics of Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9\u2010expressing neurons, proximity ligation assays, patch\u2010clamp electrophysiology in primary mouse DRG neurons and a genetic mouse model were combined to assess spatial and functional relationships between GPR35 and Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9. Pharmacological activation of GPR35 was examined using cromolyn disodium, whereas zaprinast and sildenafil were used to probe potential cGMP\u2010dependent mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      GPR35 transcripts were enriched in Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9\u2010positive neurons and proximity assays demonstrated spatial association between both proteins in DRG neurons. Activation of GPR35 with cromolyn disodium potentiated Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9 currents, accelerated channel gating and modified neuronal excitability, reflected by increased action potential overshoot and upstroke velocity. These effects were absent from GPR35\u2010deficient DRG neurons. Zaprinast and the phosphodiesterase\u20105 inhibitor sildenafil also potentiated Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9 currents in a GPR35\u2010dependent manner, indicating that cGMP\u2010associated signalling requires GPR35 expression to influence Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9. Under inflammatory conditions induced by prostaglandin E\n                      <jats:sub>2<\/jats:sub>\n                      , GPR35 activation partially attenuated Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9 potentiation but did not restore normal excitability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      These findings identify GPR35 as a regulator of Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9 and define a receptor\u2013channel signalling module linking GPCR activation to ion channel\u2013dependent modulation of sensory neuron excitability. This work provides a mechanistic framework for understanding GPCR\u2013Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9 coupling.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70529","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T02:05:16Z","timestamp":1780884316000},"page":"5336-5354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GPR35 modulates Na\n                    <sub>V<\/sub>\n                    1.9 gating and sensory neuron excitability"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-104X","authenticated-orcid":false,"given":"Margaux","family":"Theys","sequence":"first","affiliation":[{"name":"Molecular Physiology and Neurophysics Group, Department of Basic and Applied Medical Sciences University of Ghent  Ghent 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