{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:47:30Z","timestamp":1791582450106,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,12,4]],"date-time":"2014-12-04T00:00:00Z","timestamp":1417651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000963","name":"The American Diabetes Association Research Foundation","doi-asserted-by":"publisher","award":["7-08-CR-52"],"award-info":[{"award-number":["7-08-CR-52"]}],"id":[{"id":"10.13039\/100000963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Unmyelinated cutaneous axons are vulnerable to physical and metabolic injury, but also capable of rapid regeneration. This balance may help determine risk for peripheral neuropathy associated with diabetes or metabolic syndrome. Capsaicin application for 48 hours induces cutaneous fibers to die back into the dermis. Regrowth can be monitored by serial skin biopsies to determine intraepidermal nerve fiber density (IENFD). We used this capsaicin axotomy technique to examine the effects of exercise on cutaneous regenerative capacity in the setting of metabolic syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Baseline ankle IENFD and 30\u2010day cutaneous regeneration after thigh capsaicin axotomy were compared for participants with type 2 diabetes (n\u2009=\u200935) or metabolic syndrome (n\u2009=\u200932) without symptoms or examination evidence of neuropathy. Thirty\u2010six participants (17 with metabolic syndrome) then joined twice weekly observed exercise and lifestyle counseling. Axotomy regeneration was repeated in month 4 during this intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Baseline distal leg IENFD was significantly reduced for both metabolic syndrome and diabetic groups. With exercise, participants significantly improved exercise capacity and lower extremity power. Following exercise, 30\u2010day reinnervation rate improved (0.051\u2009\u00b1\u20090.027 fibers\/mm\/day before vs 0.072\u2009\u00b1\u20090.030 after exercise, <jats:italic>p<\/jats:italic>\u2009=\u20090.002). Those who achieved improvement in more metabolic syndrome features experienced a greater degree of 30\u2010day reinnervation (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.012).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Metabolic syndrome was associated with reduced baseline IENFD and cutaneous regeneration capacity comparable to that seen in diabetes. Exercise\u2010induced improvement in metabolic syndrome features increased cutaneous regenerative capacity. The results underscore the potential benefit to peripheral nerve function of a behavioral modification approach to metabolic improvement. ANN NEUROL 2015;77:146\u2013153<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24310","type":"journal-article","created":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T08:23:27Z","timestamp":1415780607000},"page":"146-153","source":"Crossref","is-referenced-by-count":107,"title":["Supervised exercise improves cutaneous reinnervation capacity in metabolic syndrome patients"],"prefix":"10.1002","volume":"77","author":[{"given":"J. Robinson","family":"Singleton","sequence":"first","affiliation":[{"name":"Departments of Neurology University of Utah Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin L.","family":"Marcus","sequence":"additional","affiliation":[{"name":"Departments of Physical Therapy University of Utah Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret K.","family":"Lessard","sequence":"additional","affiliation":[{"name":"Departments of Neurology University of Utah Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin E.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Departments of Physical Therapy University of Utah Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Gordon","family":"Smith","sequence":"additional","affiliation":[{"name":"Departments of Neurology University of Utah Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.10.2118"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20778"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23986"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2013.04.003"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2008.06.005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.60.1.108"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/848307"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-013-1681-z"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.01.029"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0047"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1663-5"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.3.830"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-21-08947.1998"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh175"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000194209.37604.57"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20550"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","unstructured":"Third report of the Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA2001;285:2486\u20132497.","DOI":"10.1001\/jama.285.19.2486"},{"key":"e_1_2_7_19_1","unstructured":"Definition diagnosis and classification of diabetes mellitus and it complications: report of a WHO consultation. Geneva Switzerland: World Health Organization 1999."},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.169404"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.17.11.1281"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2008.00180.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2010.00271.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200105033441801"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1231043"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00713504"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1249\/00005768-198205000-00012"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.2007.S5"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.17.11.1290"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-009-0070-1"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2009.07.004"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/268547"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.1088"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.07.052"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-0224"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2012.05.007"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.3.557"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.3.323"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.6.1706"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2004.09.032"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.24310","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.24310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T19:29:14Z","timestamp":1696620554000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.24310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,4]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1002\/ana.24310"],"URL":"https:\/\/doi.org\/10.1002\/ana.24310","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,4]]}}}