{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:22:16Z","timestamp":1767867736024,"version":"3.49.0"},"reference-count":61,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>The functional organization of corneal cold nerve endings, critical structures in maintaining the ocular surface, remains poorly understood. Here, the photoisomerizable small\u2010molecule diethylamine\u2010azobenzene\u2010quaternary ammonium (DENAQ) was used to photomodulate activity of cold\u2010sensing nerve terminals in control and chronic tear\u2010deficient corneas. Furthermore, DENAQ was used for in vivo photochemical regulation of the thermally induced blink reflex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Extracellular nerve terminal impulse activity was recorded on cold terminals in excised corneas of na\u00efve and tear\u2010deficient guinea pigs pre\u2010incubated with DENAQ. Pulses of light at a wavelength of 460\u2009nm were delivered to the perfused corneas. The thermally induced blink reflex was assessed using orbicularis oculi electromyography in anaesthetised rats after topical administration of DENAQ to the eye under blue light and darkness conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Exposure to blue light robustly reduced spontaneous activity of both na\u00efve and tear\u2010deficient cold nerve terminals pre\u2010incubated with DENAQ, while cold\u2010evoked responses remained unaffected. Pre\u2010incubation of excised corneas with DENAQ, along with pharmacological P2X receptor antagonists, prevented the DENAQ\u2010mediated photoreduction of the cold nerve terminal spontaneous activity. In addition, blue light increased cold\u2010evoked reflex blink in eyes pre\u2010treated with DENAQ.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      DENAQ enters guinea pig cold sensory nerve endings primarily through P2X channels in excised corneas. Subsequently, DENAQ decreases the spontaneous nerve terminal impulse activity upon light irradiation by modulating voltage\u2010gated potassium (K\n                      <jats:sub>V<\/jats:sub>\n                      ) channel activity. Furthermore, the cold\u2010evoked blink reflex is modulated by light in DENAQ\u2010treated eyes. Chemical photoswitches like DENAQ might be potential new treatments for ocular discomfort and pain in dry eye disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70189","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:34:55Z","timestamp":1759106095000},"page":"545-559","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optochemical modulation of corneal cold nerve terminal impulse activity with a photochromic ion channel blocker"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9222-4268","authenticated-orcid":false,"given":"David","family":"Ares\u2010Su\u00e1rez","sequence":"first","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2013CSIC  Sant Joan d'Alacant Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante  Alicante Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4368-5495","authenticated-orcid":false,"given":"Almudena","family":"I\u00f1igo\u2010Portugu\u00e9s","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2013CSIC  Sant Joan d'Alacant Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7299-0750","authenticated-orcid":false,"given":"Enrique","family":"Velasco","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2013CSIC  Sant Joan d'Alacant Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9977-357X","authenticated-orcid":false,"given":"Susana","family":"Quirce","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2013CSIC  Sant Joan d'Alacant Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4739-5033","authenticated-orcid":false,"given":"Fernando","family":"Aleixandre\u2010Carrera","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2013CSIC  Sant Joan d'Alacant Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1163-5987","authenticated-orcid":false,"given":"Ariadna","family":"D\u00edaz\u2010Tahoces","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2013CSIC  Sant Joan d'Alacant Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Carmen","family":"Acosta","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2013CSIC  Sant Joan d'Alacant Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7842-3036","authenticated-orcid":false,"given":"Wan\u2010Chen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology University of California  Berkeley California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8755-9389","authenticated-orcid":false,"given":"Richard H.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology University of California  Berkeley California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-5942","authenticated-orcid":false,"given":"Carlos","family":"Belmonte","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2013CSIC  Sant Joan d'Alacant Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3559-3649","authenticated-orcid":false,"given":"Juana","family":"Gallar","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2013CSIC  Sant Joan d'Alacant Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante  Alicante Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7686-6228","authenticated-orcid":false,"given":"Victor","family":"Meseguer","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2013CSIC  Sant Joan d'Alacant Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1998.0656"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.07.037"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020481"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16182"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16178"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705652"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.002"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb12781.x"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199904060-00037"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00343.2011"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0493a.x"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.110130"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.211bf.x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bja.a013473"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/377428a0"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_12_20_1","first-page":"348","article-title":"Nociceptors of the cat and rat cornea are not excited by P2X purinoceptor agonists","volume":"122","author":"Dowd E.","year":"1997","journal-title":"British Journal of Pharmacology \u2010 Proceedings Supplement"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702080"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1988.tb11427.x"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0301-0082(01)00005-3"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0304-3940(98)00656-9"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02162-7"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128951"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8118"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241612620"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-20033"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21949"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4744"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.111559"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb12979.x"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-021-03516-6"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2012.07.016"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4293"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000455"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36806-4"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/377432a0"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902030414"},{"key":"e_1_2_12_42_1","first-page":"128","article-title":"Effects of ATP on sensory receptors in the dental pulp of cats","volume":"504","author":"Matthews B.","year":"1997","journal-title":"Journal of Physiology (London)"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.08.003"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044643"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1897"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/cn200037p"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2013.00005"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.048587"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.04.025"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2264"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1993.70.6.2370"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0b013e3180339f6e"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8150"},{"key":"e_1_2_12_55_1","unstructured":"Quirce S.(2020).Actividad de los nervios sensoriales de la c\u00f3rnea durante la deficiencia lagrimal cr\u00f3nica y su modulaci\u00f3n farmacol\u00f3gica.https:\/\/dspace.umh.es\/"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.09.035"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.020701"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.05.039"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.08.038"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.01.003"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2013.4399"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-895X(24)13265-8"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70189","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T03:53:20Z","timestamp":1767844400000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,28]]},"references-count":61,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/bph.70189"],"URL":"https:\/\/doi.org\/10.1111\/bph.70189","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,28]]},"assertion":[{"value":"2024-11-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}