{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:23:56Z","timestamp":1792736636040,"version":"4.5.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T00:00:00Z","timestamp":1517875200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T00:00:00Z","timestamp":1517875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Biomed Eng"],"DOI":"10.1038\/s41551-018-0192-3","type":"journal-article","created":{"date-parts":[[2018,2,3]],"date-time":"2018-02-03T19:09:32Z","timestamp":1517684972000},"page":"114-123","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Treatment of chronic pain by designer cells controlled by spearmint aromatherapy"],"prefix":"10.1038","volume":"2","author":[{"given":"Hui","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5657-532X","authenticated-orcid":false,"given":"Mingqi","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghislaine","family":"Charpin-El Hamri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8545-667X","authenticated-orcid":false,"given":"Martin","family":"Fussenegger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,2,6]]},"reference":[{"key":"192_CR1","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s00424-009-0779-3","volume":"460","author":"A Lampert","year":"2010","unstructured":"Lampert, A., O\u2019Reilly, A. O., Reeh, P. & Leffler, A. Sodium channelopathies and pain. Pflug. Arch. Eur. J. Phy. 460, 249\u2013263 (2010).","journal-title":"Pflug. Arch. Eur. J. Phy."},{"key":"192_CR2","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1021\/cn500171p","volume":"5","author":"GF King","year":"2014","unstructured":"King, G. F. & Vetter, I. No gain, no pain: NaV1.7 as an analgesic target. ACS Chem. Neurosci. 5, 749\u2013751 (2014).","journal-title":"ACS Chem. Neurosci."},{"key":"192_CR3","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.nbd.2012.05.005","volume":"48","author":"WF Goins","year":"2012","unstructured":"Goins, W. F., Cohen, J. B. & Glorioso, J. C. Gene therapy for the treatment of chronic peripheral nervous system pain. Neurobiol. Dis. 48, 255\u2013270 (2012).","journal-title":"Neurobiol. Dis."},{"key":"192_CR4","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nrn3404","volume":"14","author":"SD Dib-Hajj","year":"2013","unstructured":"Dib-Hajj, S. D., Yang, Y., Black, J. A. & Waxman, S. G. The NaV1.7 sodium channel: from molecule to man. Nat. Rev. Neurosci. 14, 49\u201362 (2013).","journal-title":"Nat. Rev. Neurosci."},{"key":"192_CR5","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1126\/science.aan0088","volume":"355","author":"T Grosser","year":"2017","unstructured":"Grosser, T., Woolf, C. J. & FitzGerald, G. A. Time for nonaddictive relief of pain. Science 355, 1026\u20131027 (2017).","journal-title":"Science"},{"key":"192_CR6","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1111\/j.1476-5381.2011.01781.x","volume":"166","author":"DJ Adams","year":"2012","unstructured":"Adams, D. J., Callaghan, B. & Berecki, G. Analgesic conotoxins: block and G protein-coupled receptor modulation of N-type (CaV2.2) calcium channels. Br. J. Pharmacol. 166, 486\u2013500 (2012).","journal-title":"Br. J. Pharmacol."},{"key":"192_CR7","doi-asserted-by":"publisher","first-page":"69","DOI":"10.2147\/nedt.2007.3.1.69","volume":"3","author":"JG McGivern","year":"2007","unstructured":"McGivern, J. G. Ziconotide: a review of its pharmacology and use in the treatment of pain. Neuropsychiatr. Dis. Treat. 3, 69\u201385 (2007).","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"192_CR8","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.peptides.2013.03.011","volume":"44","author":"JD Revell","year":"2013","unstructured":"Revell, J. D. et al. Potency optimization of Huwentoxin-IV on hNav1.7: a neurotoxin TTX-S sodium-channel antagonist from the venom of the Chinese bird-eating spider Selenocosmia huwena. Peptides 44, 40\u201346 (2013).","journal-title":"Peptides"},{"key":"192_CR9","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.1021\/jm501765v","volume":"58","author":"JK Murray","year":"2015","unstructured":"Murray, J. K. et al. Engineering potent and selective analogues of GpTx-1, a tarantula venom peptide antagonist of the NaV1.7 sodium channel. J. Med. Chem. 58, 2299\u20132314 (2015).","journal-title":"J. Med. Chem."},{"key":"192_CR10","doi-asserted-by":"publisher","first-page":"153","DOI":"10.2174\/09298665113206660119","volume":"21","author":"Y Liu","year":"2014","unstructured":"Liu, Y. et al. Analgesic effects of Huwentoxin-IV on animal models of inflammatory and neuropathic pain. Protein Pept. Lett. 21, 153\u2013158 (2014).","journal-title":"Protein Pept. Lett."},{"key":"192_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41551-016-0005","volume":"1","author":"H Ye","year":"2016","unstructured":"Ye, H. et al. Self-adjusting synthetic gene circuit for correcting insulin resistance. Nat. Biomed. Eng. 1, 1\u20139 (2016).","journal-title":"Nat. Biomed. Eng."},{"key":"192_CR12","doi-asserted-by":"publisher","first-page":"3676","DOI":"10.1016\/j.bmcl.2011.04.088","volume":"21","author":"S Chowdhury","year":"2011","unstructured":"Chowdhury, S. et al. Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain. Bioorg. Med. Chem. Lett. 21, 3676\u20133681 (2011).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"192_CR13","doi-asserted-by":"publisher","first-page":"E2724","DOI":"10.1073\/pnas.1220844110","volume":"110","author":"K McCormack","year":"2013","unstructured":"McCormack, K. et al. Voltage sensor interaction site for selective small molecule inhibitors of voltage-gated sodium channels. Proc. Natl Acad. Sci. USA 110, E2724\u2013E2732 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"192_CR14","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1111\/j.1476-5381.2011.01209.x","volume":"164","author":"PL Sheets","year":"2011","unstructured":"Sheets, P. L., Jarecki, B. W. & Cummins, T. R. Lidocaine reduces the transition to slow inactivation in Nav1.7 voltage-gated sodium channels. Br. J. Pharmacol. 164, 719\u2013730 (2011).","journal-title":"Br. J. Pharmacol."},{"key":"192_CR15","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nrd.2015.34","volume":"15","author":"G Gintant","year":"2016","unstructured":"Gintant, G., Sager, P. T. & Stockbridge, N. Evolution of strategies to improve preclinical cardiac safety testing. Nat. Rev. Drug Discov. 15, 457\u2013471 (2016).","journal-title":"Nat. Rev. Drug Discov."},{"key":"192_CR16","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1016\/j.cell.2014.03.064","volume":"157","author":"JH Lee","year":"2014","unstructured":"Lee, J. H. et al. A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief. Cell 157, 1393\u20131404 (2014).","journal-title":"Cell"},{"key":"192_CR17","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.pbb.2006.06.011","volume":"84","author":"KC Vissers","year":"2006","unstructured":"Vissers, K. C., Geenen, F., Biermans, R. & Meert, T. F. Pharmacological correlation between the formalin test and the neuropathic pain behavior in different species with chronic constriction injury. Pharmacol. Biochem Behav. 84, 479\u2013486 (2006).","journal-title":"Pharmacol. Biochem Behav."},{"key":"192_CR18","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/0165-0270(85)90116-5","volume":"14","author":"S Hunskaar","year":"1985","unstructured":"Hunskaar, S., Fasmer, O. B. & Hole, K. Formalin test in mice, a useful technique for evaluating mild analgesics. J. Neurosci. Methods 14, 69\u201376 (1985).","journal-title":"J. Neurosci. Methods"},{"key":"192_CR19","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S1090-3801(98)90033-7","volume":"2","author":"KJ Sufka","year":"1998","unstructured":"Sufka, K. J., Watson, G. S., Nothdurft, R. E. & Mogil, J. S. Scoring the mouse formalin test: validation study. Eur. J. Pain. 2, 351\u2013358 (1998).","journal-title":"Eur. J. Pain."},{"key":"192_CR20","doi-asserted-by":"publisher","first-page":"7228","DOI":"10.1021\/bi2008596","volume":"50","author":"T Dahoun","year":"2011","unstructured":"Dahoun, T., Grasso, L., Vogel, H. & Pick, H. Recombinant expression and functional characterization of mouse olfactory receptor mOR256-17 in mammalian cells. Biochemistry 50, 7228\u20137235 (2011).","journal-title":"Biochemistry"},{"key":"192_CR21","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1038\/nprot.2009.100","volume":"4","author":"N Sun","year":"2009","unstructured":"Sun, N., Lee, A. & Wu, J. C. Long term non-invasive imaging of embryonic stem cells using reporter genes. Nat. Protoc. 4, 1192\u20131201 (2009).","journal-title":"Nat. Protoc."},{"key":"192_CR22","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.cell.2004.11.021","volume":"119","author":"H Saito","year":"2004","unstructured":"Saito, H., Kubota, M., Roberts, R. W., Chi, Q. & Matsunami, H. RTP family members induce functional expression of mammalian odorant receptors. Cell 119, 679\u2013691 (2004).","journal-title":"Cell"},{"key":"192_CR23","first-page":"79","volume":"16","author":"J Reichling","year":"2009","unstructured":"Reichling, J., Schnitzler, P., Suschke, U. & Saller, R. Essential oils of aromatic plants with antibacterial, antifungal, antiviral, and cytotoxic properties\u2014an overview. Forsch. Komplementmed. 16, 79\u201390 (2009).","journal-title":"Forsch. Komplementmed."},{"key":"192_CR24","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/nchembio.2281","volume":"13","author":"M Muller","year":"2017","unstructured":"Muller, M. et al. Designed cell consortia as fragrance-programmable analog-to-digital converters. Nat. Chem. Biol. 13, 309\u2013316 (2017).","journal-title":"Nat. Chem. Biol."},{"key":"192_CR25","doi-asserted-by":"crossref","unstructured":"Ni, C. H. et al. The anxiolytic effect of aromatherapy on patients awaiting ambulatory surgery: a randomized controlled trial. Evid. Based Compl. Alt. 2013, 927419 (2013).","DOI":"10.1155\/2013\/927419"},{"key":"192_CR26","doi-asserted-by":"crossref","unstructured":"Bilia, A. R. et al. Essential oils loaded in nanosystems: a developing strategy for a successful therapeutic approach. Evid. Based Compl. Alt. 2014, 651593 (2014).","DOI":"10.1155\/2014\/651593"},{"key":"192_CR27","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1038\/nm.2123","volume":"16","author":"ZZ Xu","year":"2010","unstructured":"Xu, Z. Z. et al. Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions. Nat. Med. 16, 592\u2013597 (2010).","journal-title":"Nat. Med."},{"key":"192_CR28","first-page":"1540","volume":"7","author":"C Liu","year":"2012","unstructured":"Liu, C., Cao, J., Ren, X. & Zang, W. Nav1.7 protein and mRNA expression in the dorsal root ganglia of rats with chronic neuropathic pain. Neural Regen. Res. 7, 1540\u20131544 (2012).","journal-title":"Neural Regen. Res."},{"key":"192_CR29","doi-asserted-by":"publisher","first-page":"3753","DOI":"10.1172\/JCI43195","volume":"120","author":"G Burgess","year":"2010","unstructured":"Burgess, G. & Williams, D. The discovery and development of analgesics: new mechanisms, new modalities.  J. Clin. Investig. 120, 3753\u20133759 (2010).","journal-title":"J. Clin. Investig."},{"key":"192_CR30","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1038\/nature05413","volume":"444","author":"JJ Cox","year":"2006","unstructured":"Cox, J. J. et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature 444, 894\u2013898 (2006).","journal-title":"Nature"},{"key":"192_CR31","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1002\/biot.201400642","volume":"10","author":"M Xie","year":"2015","unstructured":"Xie, M. & Fussenegger, M. Mammalian designer cells: engineering principles and biomedical applications. Biotechnol. J. 10, 1005\u20131018 (2015).","journal-title":"Biotechnol. J."},{"key":"192_CR32","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/nrm.2016.10","volume":"17","author":"A Trounson","year":"2016","unstructured":"Trounson, A. & DeWitt, N. D. Pluripotent stem cells progressing to the clinic. Nat. Rev. Mol. Cell Biol. 17, 194\u2013200 (2016).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"192_CR33","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/j.biomaterials.2013.09.071","volume":"35","author":"A Lathuiliere","year":"2014","unstructured":"Lathuiliere, A., Cosson, S., Lutolf, M. P., Schneider, B. L. & Aebischer, P. A high-capacity cell macroencapsulation system supporting the long-term survival of genetically engineered allogeneic cells. Biomaterials 35, 779\u2013791 (2014).","journal-title":"Biomaterials"},{"key":"192_CR34","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.cbpb.2005.12.010","volume":"143","author":"JR Prohaska","year":"2006","unstructured":"Prohaska, J. R. & Broderius, M. Plasma peptidylglycine alpha-amidating monooxygenase (PAM) and ceruloplasmin are affected by age and copper status in rats and mice. Comp. Biochem. Phys. B 143, 360\u2013366 (2006).","journal-title":"Comp. Biochem. Phys. B"},{"key":"192_CR35","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/0141-0229(94)90014-0","volume":"16","author":"DJ Merkler","year":"1994","unstructured":"Merkler, D. J. C-terminal amidated peptides: production by the in vitro enzymatic amidation of glycine-extended peptides and the importance of the amide to bioactivity. Enzym. Microb. Technol. 16, 450\u2013456 (1994).","journal-title":"Enzym. Microb. Technol."},{"key":"192_CR36","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1126\/science.aaf4006","volume":"354","author":"M Xie","year":"2016","unstructured":"Xie, M. et al. beta-cell-mimetic designer cells provide closed-loop glycemic control. Science 354, 1296\u20131301 (2016).","journal-title":"Science"},{"key":"192_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-10-26","volume":"10","author":"RP Bonin","year":"2014","unstructured":"Bonin, R. P., Bories, C. & De Koninck, Y. A simplified up-down method (SUDO) for measuring mechanical nociception in rodents using von Frey filaments. Mol. Pain. 10, 26 (2014).","journal-title":"Mol. Pain."},{"key":"192_CR38","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1016\/j.celrep.2016.04.063","volume":"15","author":"F Denk","year":"2016","unstructured":"Denk, F., Crow, M., Didangelos, A., Lopes, D. M. & McMahon, S. B. Persistent alterations in microglial enhancers in a model of chronic pain. Cell Rep. 15, 1771\u20131781 (2016).","journal-title":"Cell Rep."},{"key":"192_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/srep40968","volume":"7","author":"AM Hassan","year":"2017","unstructured":"Hassan, A. M. et al. Visceral hyperalgesia caused by peptide YY deletion and Y2 receptor antagonism. Sci. Rep. 7, 40968 (2017).","journal-title":"Sci. Rep."},{"key":"192_CR40","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0165-0270(94)90144-9","volume":"53","author":"SR Chaplan","year":"1994","unstructured":"Chaplan, S. R., Bach, F. W., Pogrel, J. W., Chung, J. M. & Yaksh, T. L. Quantitative assessment of tactile allodynia in the rat paw. J. Neurosci. Methods 53, 55\u201363 (1994).","journal-title":"J. Neurosci. Methods"},{"key":"192_CR41","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/ilar.40.3.111","volume":"40","author":"K Ren","year":"1999","unstructured":"Ren, K. & Dubner, R. Inflammatory models of pain and hyperalgesia. ILAR J. 40, 111\u2013118 (1999).","journal-title":"ILAR J."},{"key":"192_CR42","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1111\/jth.13684","volume":"15","author":"K Beko","year":"2017","unstructured":"Beko, K. et al. Contribution of platelet P2Y12 receptors to chronic Complete Freund\u2019s adjuvant-induced inflammatory pain. J. Thromb. Haemost. 15, 1223\u20131235 (2017).","journal-title":"J. Thromb. Haemost."},{"key":"192_CR43","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/0304-3959(88)90209-6","volume":"33","author":"GJ Bennett","year":"1988","unstructured":"Bennett, G. J. & Xie, Y. K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33, 87\u2013107 (1988).","journal-title":"Pain"},{"key":"192_CR44","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/1471-2105-7-123","volume":"7","author":"HJ Motulsky","year":"2006","unstructured":"Motulsky, H. J. & Brown, R. E. Detecting outliers when fitting data with nonlinear regression\u2014a new method based on robust nonlinear regression and the false discovery rate. BMC Bioinformatics 7, 123 (2006).","journal-title":"BMC Bioinformatics"},{"key":"192_CR45","doi-asserted-by":"publisher","first-page":"e91","DOI":"10.1093\/nar\/gkv326","volume":"43","author":"H Wang","year":"2015","unstructured":"Wang, H., Ye, H., Xie, M., Daoud El-Baba, M. & Fussenegger, M. Cosmetics-triggered percutaneous remote control of transgene expression in mice. Nucleic Acids Res. 43, e91 (2015).","journal-title":"Nucleic Acids Res."},{"key":"192_CR46","doi-asserted-by":"crossref","unstructured":"Branson, K. Distinguishing seemingly indistinguishable animals with computer vision. Nat. Methods 11, 721\u2013722 (2014).","DOI":"10.1038\/nmeth.3004"}],"container-title":["Nature Biomedical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41551-018-0192-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-018-0192-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-018-0192-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T23:32:48Z","timestamp":1671579168000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41551-018-0192-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,6]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,2]]}},"alternative-id":["192"],"URL":"https:\/\/doi.org\/10.1038\/s41551-018-0192-3","relation":{},"ISSN":["2157-846X"],"issn-type":[{"value":"2157-846X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,6]]},"assertion":[{"value":"9 May 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}