{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:14:38Z","timestamp":1793304878930,"version":"4.5.0"},"reference-count":63,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS097590"],"award-info":[{"award-number":["R01 NS097590"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009012","name":"Veterans Affairs San Diego Healthcare System","doi-asserted-by":"publisher","award":["1I01RX002484"],"award-info":[{"award-number":["1I01RX002484"]}],"id":[{"id":"10.13039\/100009012","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    SP16 is an innovative peptide derived from the carboxyl\u2010terminus of \u03b11\u2010Antitrypsin (AAT), corresponding to residues 364\u2010380, and contains recognition sequences for the low\u2010density lipoprotein receptor\u2010related protein\u20101 (LRP1). LRP1 is an endocytic and cell\u2010signaling receptor that regulates inflammation. Deletion of\n                    <jats:italic>Lrp1<\/jats:italic>\n                    in Schwann cells increases neuropathic pain; however, the role of LRP1 activation in nociceptive and neuropathic pain regulation remains unknown. Herein, we show that SP16 is bioactive in sensory neurons in vitro. Neurite length and regenerative gene expression were increased by SP16. In PC12 cells, SP16 activated Akt and ERK1\/2 cell\u2010signaling in an LRP1\u2010dependent manner. When formalin was injected into mouse hind paws, to model inflammatory pain, SP16 dose\u2010dependently attenuated nociceptive pain behaviors in the early and late phases. In a second model of acute pain using capsaicin, SP16\u00a0significantly reduced paw licking in both male and female mice (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a0.01) similarly to enzymatically inactive tissue plasminogen activator, a known LRP1 interactor. SP16 also prevented development of tactile allodynia after partial nerve ligation and this response was sustained for nine days (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a0.01). Immunoblot analysis of the injured nerve revealed decreased CD11b (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a0.01) and Toll\u2010like receptor\u20104 (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a0.005). In injured dorsal root ganglia SP16 reduced CD11b\n                    <jats:sup>+<\/jats:sup>\n                    cells (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a0.05) and GFAP (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a0.005), indicating that inflammatory cell recruitment and satellite cell activation were inhibited. In conclusion, administration of SP16 blocked pain\u2010related responses in three distinct pain models, suggesting efficacy against acute nociceptive, inflammatory, and neuropathic pain. SP16 also attenuated innate immunity in the PNS. These studies identify SP16 as a potentially effective treatment for pain.\n                  <\/jats:p>","DOI":"10.1096\/fj.202101031rr","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T02:29:20Z","timestamp":1639103360000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["\u03b11\u2010Antitrypsin derived SP16 peptide demonstrates efficacy in rodent models of acute and neuropathic pain"],"prefix":"10.1096","volume":"36","author":[{"given":"Zixuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology School of Medicine University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Martellucci","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology School of Medicine University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Van Enoo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology School of Medicine University of California, San Diego  La Jolla California USA"},{"name":"Program in Neurosciences University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Austin","sequence":"additional","affiliation":[{"name":"Serpin Pharma  Manassas Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cohava","family":"Gelber","sequence":"additional","affiliation":[{"name":"Serpin Pharma  Manassas Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy M.","family":"Campana","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology School of Medicine University of California, San Diego  La Jolla California USA"},{"name":"Program in Neurosciences University of California, San Diego  La Jolla California USA"},{"name":"San Diego Veterans Administration Health Care System  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.06.017"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2018.08.005"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010med\u2010011817\u2010044739"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00033.2007"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.08.029"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)99160\u2010X"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.11.6523"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2005.03.019"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212592200"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010386471\u20100.00002\u2010X"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2017.05.007"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2019.00051"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0247357"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201004\u2010780205"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20628"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224738"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001306"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3257\u201018.2019"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010016\u20100343\u20102"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23599"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1999.4590"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0410220"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.3342\u201012.2013"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/PR9.0000000000000898"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.509133"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.478552"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14891"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000188"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)54845\u20106"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.3053\u201008.2008"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24098"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103959(90)91074\u2010S"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165\u20100270(94)90144\u20109"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23325"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000000691"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.9.1145"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103959(87)90088\u20101"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010020\u201000713\u20104"},{"issue":"2","key":"e_1_2_9_40_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0031-6997(25)06664-5","article-title":"Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons","volume":"43","author":"Holzer P","year":"1991","journal-title":"Pharmacol Rev"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5464.306"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kex308"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201013839\u20102"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201901921R"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201018642\u2010y"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010020\u20100333\u2010z"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20872"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71389"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432\u20101033.2003.03793.x"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.31.18604"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.650911"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.010449"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.10002\/jgm.180"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2709\u201006.2006"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542\u2010199210000\u201000021"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.12\u201009\u201003665.1992"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000163542.48611.A2"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2008.05492.x"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.1956\u201015.2015"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax6452"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2009.04.020"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21783"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60223"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2021.01.001"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202101031RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202101031RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202101031RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T01:05:49Z","timestamp":1761699949000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202101031RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,9]]},"references-count":63,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1096\/fj.202101031RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202101031rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,9]]},"assertion":[{"value":"2021-06-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22093"}}