{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:40:56Z","timestamp":1789713656013,"version":"4.0.1"},"reference-count":59,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2018,9,9]],"date-time":"2018-09-09T00:00:00Z","timestamp":1536451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21432003"],"award-info":[{"award-number":["21432003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673282"],"award-info":[{"award-number":["81673282"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The voltage\u2010gated sodium channel Na<jats:sub>V<\/jats:sub>1.7 is considered a therapeutic target for pain treatment based on human genetic evidence. GpTx\u20101 and its potent analogue [Ala<jats:sup>5<\/jats:sup>, Phe<jats:sup>6<\/jats:sup>, Leu<jats:sup>26<\/jats:sup>, Arg<jats:sup>28<\/jats:sup>]GpTx\u20101 (GpTx\u20101\u201071) were recently characterized as Na<jats:sub>V<\/jats:sub>1.7 inhibitors<jats:italic>in vitro<\/jats:italic>. Furthermore, the present work was conducted to investigate the analgesic properties of these two peptides in different pain models after spinal administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The antinociceptive activities of both GpTx\u20101 and GpTx\u20101\u201071 were investigated in mouse models of acute, visceral, inflammatory and neuropathic pain. Furthermore, the side effects of GpTx\u20101 and GpTx\u20101\u201071 were evaluated in rotarod, antinociceptive tolerance, acute hyperlocomotion and gastrointestinal transit tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The i.t. administration of both GpTx\u20101 and GpTx\u20101\u201071 dose\u2010dependently produced powerful antinociception in the different pain models. This effect was attenuated by the opioid receptor antagonist naloxone, suggesting the involvement of the opioid system. In this study, repeated administration of these two_peptides produced spinal analgesia without a loss of potency over 8\u00a0days in mouse models of acute, inflammatory and neuropathic pain. Moreover, spinal administration of GpTx\u20101 and GpTx\u20101\u201071 did not induce significant effects on motor coordination, evoke acute hyperlocomotion or increase gastrointestinal transit time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our data indicate that the Na<jats:sub>V<\/jats:sub>1.7 peptide inhibitors GpTx\u20101 and GpTx\u20101\u201071 produce powerful, nontolerance\u2010forming analgesia in preclinical pain models, which might be dependent on the endogenous opioid system. In addition, at the spinal level, the limited side effects imply that these Na<jats:sub>V<\/jats:sub>1.7 peptide inhibitors could be potentially developed as GpTx\u20101\u2010based drugs for pain relief.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14461","type":"journal-article","created":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T06:49:53Z","timestamp":1533624593000},"page":"3911-3927","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["<scp>G<\/scp>p<scp>T<\/scp>x\u20101 and [<scp>A<\/scp>la<sup>5<\/sup>,<scp>P<\/scp>he<sup>6<\/sup>,<scp>L<\/scp>eu<sup>26<\/sup>,<scp>A<\/scp>rg<sup>28<\/sup>]<scp>G<\/scp>p<scp>T<\/scp>x\u20101, two peptide<scp>N<\/scp>a<sub>V<\/sub>1.7 inhibitors: analgesic and tolerance properties at the spinal level"],"prefix":"10.1111","volume":"175","author":[{"given":"Chao","family":"Chen","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Nano\u2010Micro Materials Research, School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuerui","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengna","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilong","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0381-6796","authenticated-orcid":false,"given":"Quan","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13879"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13884"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152405"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-018-0203-0"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb08534.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.015941"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.4.4"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2013.10.029"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05413"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.7.11.1597"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40883"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins8030078"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-060909-153234"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2660(08)01004-3"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(03)00177-5"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws225"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22485"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91608-U"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2007.09.032"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(80)90515-4"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002508-200207001-00002"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(87)90671-0"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.064"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13489"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12789"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9918.1"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000000202"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.2174\/09298665113206660119"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.05.041"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19112"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1940"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220844110"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001227"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9967"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501765v"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301471"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2507-05.2005"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404915101"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2011.06.006"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.03.017"},{"key":"e_1_2_10_45_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S0022-3565(25)21992-9","article-title":"The spinal cord as a site of opioid effects on gastrointestinal transit in the mouse","volume":"227","author":"Porreca F","year":"1983","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.03.042"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.108.047670"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-4328(82)90063-8"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.041046"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.01.076"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2014.02.007"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002508-200006001-00014"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.21437"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b01181"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b06506"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000453"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1306285110"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30005-4"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2017.07.044"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2017.12.013"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.14461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T06:57:36Z","timestamp":1751785056000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.14461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,9]]},"references-count":59,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1111\/bph.14461"],"URL":"https:\/\/doi.org\/10.1111\/bph.14461","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,9]]},"assertion":[{"value":"2018-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}