{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:31:50Z","timestamp":1786509110635,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"crossref","award":["2022\/08212-6"],"award-info":[{"award-number":["2022\/08212-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"crossref","award":["2014\/24660-2"],"award-info":[{"award-number":["2014\/24660-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"crossref","award":["2013\/01274-7"],"award-info":[{"award-number":["2013\/01274-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2022\/08212-6"],"award-info":[{"award-number":["2022\/08212-6"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2014\/24660-2"],"award-info":[{"award-number":["2014\/24660-2"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2013\/01274-7"],"award-info":[{"award-number":["2013\/01274-7"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Neuropathic pain is a chronic condition frequently associated with peripheral nerve injury and is characterized by significant structural and molecular alterations. Photobiomodulation therapy (PBMT) has demonstrated analgesic and anti-inflammatory effects; however, its influence on neurotrophic and myelin-associated repair mechanisms remains incompletely understood. The aim of this study was to investigate the effects of PBMT on ultrastructural, morphometric, and molecular changes induced by chronic constriction injury (CCI) of the sciatic nerve in male rats, with an emphasis on NGF and P0 expression. Neuropathy was induced using the CCI model of the sciatic nerve. PBMT was initiated 14 days after injury and administered in ten sessions using an infrared 904 nm laser. Transmission electron microscopy, morphometric analysis, immunofluorescence, and Western blot analyses were performed to evaluate neural regeneration and the expression of NGF and P0. Animals subjected to CCI exhibited ultrastructural changes consistent with Wallerian degeneration, accompanied by reduced NGF and P0 expression in the sciatic nerve. In contrast, PBMT markedly preserved nerve morphology, restored NGF expression, and significantly increased P0 protein levels. Together, these findings demonstrate that PBMT enhances peripheral nerve repair by promoting both molecular and structural mechanisms involved in axonal regeneration and myelin restoration. Restoration of NGF expression and increased P0 protein expression suggest that these mechanisms contribute to the regenerative effects of PBMT, supporting its potential as a safe, noninvasive therapeutic strategy for peripheral neuropathies.<\/jats:p>","DOI":"10.3390\/cimb48080806","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:23:50Z","timestamp":1786357430000},"page":"806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Photobiomodulation Therapy Enhances Peripheral Nerve Repair by Restoring Nerve Growth Factor Levels and Increasing Myelin Protein Zero Expression After Chronic Constriction Injury in Rats"],"prefix":"10.3390","volume":"48","author":[{"given":"Mara Evany","family":"Oliveira","sequence":"first","affiliation":[{"name":"Functional Neuroanatomy of Pain Laboratory, Department of Anatomy, Institute of Biomedical Sciences, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05508-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0415-1960","authenticated-orcid":false,"given":"Fabio Martinez","family":"Santos","sequence":"additional","affiliation":[{"name":"Functional Neuroanatomy of Pain Laboratory, Department of Anatomy, Institute of Biomedical Sciences, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05508-900, Brazil"},{"name":"Department of Morphology and Genetics, Paulista School of Medicine, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04023-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2912-3376","authenticated-orcid":false,"given":"Adriano Polican","family":"Ciena","sequence":"additional","affiliation":[{"name":"Morphology and Physical Activity Laboratory (LAMAF), Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Rio Claro 13506-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0172-4110","authenticated-orcid":false,"given":"Marucia","family":"Chacur","sequence":"additional","affiliation":[{"name":"Functional Neuroanatomy of Pain Laboratory, Department of Anatomy, Institute of Biomedical Sciences, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05508-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S0306-4522(96)00422-8","article-title":"Persisting sensitization of the behavioural response to formalin-induced injury in the rat through activation of serotonin2A receptors","volume":"77","author":"Abbott","year":"1997","journal-title":"Neuroscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.pain.2007.08.013","article-title":"Prevalence of chronic pain with neuropathic characteristics in the general population","volume":"136","author":"Bouhassira","year":"2008","journal-title":"Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.neuron.2006.09.021","article-title":"Mechanisms of neuropathic pain","volume":"52","author":"Campbell","year":"2006","journal-title":"Neuron"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"f7656","DOI":"10.1136\/bmj.f7656","article-title":"Neuropathic pain: Mechanisms and their clinical implications","volume":"348","author":"Cohen","year":"2014","journal-title":"BMJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0304-3959(91)90165-T","article-title":"Thermographic observations on rats with experimental neuropathic pain","volume":"45","author":"Bennett","year":"1991","journal-title":"Pain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0304-3959(88)90209-6","article-title":"A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man","volume":"33","author":"Bennett","year":"1988","journal-title":"Pain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1002\/1097-4598(2000)999:9<::AID-MUS7>3.0.CO;2-F","article-title":"The microenvironment of injured and regenerating peripheral nerves","volume":"9","author":"Zochodne","year":"2000","journal-title":"Muscle Nerve Suppl."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3109\/08977194.2014.953630","article-title":"Neural mobilization promotes nerve regeneration by nerve growth factor and myelin protein zero increased after sciatic nerve injury","volume":"33","author":"Santos","year":"2015","journal-title":"Growth Factors"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/micr.20055","article-title":"Beneficial effect of nerve growth factor-7S on peripheral nerve regeneration through inside-out vein grafts: An experimental study","volume":"24","author":"Gravvanis","year":"2004","journal-title":"Microsurgery"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1017\/S0317167100009331","article-title":"Peripheral sensory axon growth: From receptor binding to cellular signaling","volume":"35","author":"Tucker","year":"2008","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.pharmthera.2005.06.003","article-title":"Molecular mechanisms of neuropathic pain\u2014Phenotypic switch and initiation mechanisms","volume":"109","author":"Ueda","year":"2006","journal-title":"Pharmacol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1002\/mus.21062","article-title":"Axonal neuropathy due to myelin protein zero mutation misdiagnosed as amyloid neuropathy","volume":"38","author":"Briani","year":"2008","journal-title":"Muscle Nerve"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"20111","DOI":"10.1074\/jbc.M109.022426","article-title":"Induction of myelin protein zero by early growth response 2 through upstream and intragenic elements","volume":"284","author":"Jang","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jphotobiol.2016.08.025","article-title":"Use of low level laser therapy to control neuropathic pain: A systematic review","volume":"164","author":"Bossini","year":"2016","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_15","first-page":"58","article-title":"Biological effects of low level laser therapy","volume":"5","author":"Farivar","year":"2014","journal-title":"J. Lasers Med. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1039\/c6pp00360e","article-title":"Low level laser therapy alters satellite glial cell expression and reverses nociceptive behavior in rats with neuropathic pain","volume":"16","author":"Oliveira","year":"2017","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1007\/s10103-020-03187-9","article-title":"Effects of photobiomodulation therapy on neuropathic pain in rats: Evaluation of nociceptive mediators and infrared thermography","volume":"36","author":"Brioschi","year":"2021","journal-title":"Lasers Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0304-3959(83)90201-4","article-title":"Ethical guidelines for investigations of experimental pain in conscious animals","volume":"16","author":"Zimmermann","year":"1983","journal-title":"Pain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"114680","DOI":"10.1016\/j.physbeh.2024.114680","article-title":"Prevention and reversal of neuropathic pain by near-infrared photobiomodulation therapy in male and female rats","volume":"286","author":"Chacur","year":"2024","journal-title":"Physiol. Behav."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.micron.2011.08.009","article-title":"Fine structure of myotendinous junction between the anterior belly of the digastric muscle and intermediate tendon in adults rats","volume":"43","author":"Ciena","year":"2012","journal-title":"Micron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1679\/aohc.46.173","article-title":"The fine structure of lamellated nerve endings found in the rat gingiva","volume":"46","author":"Watanabe","year":"1983","journal-title":"Arch. Histol. Jpn."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s43630-021-00018-w","article-title":"Effect of photobiomodulation on mitochondrial dynamics in peripheral nervous system in streptozotocin-induced type 1 diabetes in rats","volume":"20","author":"Rocha","year":"2021","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s10103-024-04171-3","article-title":"Unraveling the RAGE-NF-\u03baB pathway: Implications for modulating inflammation in diabetic neuropathy through photobiomodulation therapy","volume":"39","author":"Ferreira","year":"2024","journal-title":"Lasers Med. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4350","DOI":"10.1073\/pnas.76.9.4350","article-title":"Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications","volume":"76","author":"Towbin","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chen, Y.J., Wang, Y.H., Wang, C.Z., Ho, M.L., Kuo, P.L., Huang, M.H., and Chen, C.H. (2014). Effect of low level laser therapy on chronic compression of the dorsal root ganglion. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089894"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s10103-013-1323-4","article-title":"Potential anti-inflammatory effect of low-level laser therapy on the experimental reflux laryngitis: A preliminary study","volume":"29","author":"Marinho","year":"2014","journal-title":"Lasers Med. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1007\/s10103-017-2284-9","article-title":"Photobiomodulation therapy by NIR laser in persistent pain: An analytical study in the rat","volume":"32","author":"Micheli","year":"2017","journal-title":"Lasers Med. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jchemneu.2017.04.005","article-title":"The role of low level laser therapy on neuropathic pain relief and interleukin-6 expression following spinal cord injury: An experimental study","volume":"87","author":"Mojarad","year":"2018","journal-title":"J. Chem. Neuroanat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s10103-013-1355-9","article-title":"Effects of early and delayed laser application on nerve regeneration","volume":"29","author":"Akgul","year":"2014","journal-title":"Lasers Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1179\/016164104225013914","article-title":"Phototherapy promotes regeneration and functional recovery of injured peripheral nerve","volume":"26","author":"Anders","year":"2004","journal-title":"Neurol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s10103-011-1008-9","article-title":"Low-level laser therapy improves repair following complete resection of the sciatic nerve in rats","volume":"27","author":"Medalha","year":"2012","journal-title":"Lasers Med. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.brainres.2011.01.098","article-title":"Schwann-like mesenchymal stem cells within vein graft facilitate facial nerve regeneration and remyelination","volume":"1383","author":"Wang","year":"2011","journal-title":"Brain Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nrn1078","article-title":"Neurotrophins and their receptors: A convergence point for many signalling pathways","volume":"4","author":"Chao","year":"2003","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1097\/00001756-199705060-00012","article-title":"NGF involvement in pain induced by chronic constriction injury of the rat sciatic nerve","volume":"8","author":"Herzberg","year":"1997","journal-title":"Neuroreport"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0304-3959(98)00164-X","article-title":"Effect of NGF and anti-NGF on neuropathic pain in rats following chronic constriction injury of the sciatic nerve","volume":"79","author":"Ro","year":"1999","journal-title":"Pain"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s10103-017-2181-2","article-title":"Neuropeptide expression and morphometric differences in crushed alveolar inferior nerve of rats: Effects of photobiomodulation","volume":"32","author":"Martins","year":"2017","journal-title":"Lasers Med. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1159\/000145717","article-title":"Characterization of the shark myelin Po protein","volume":"72","author":"Rotenstein","year":"2008","journal-title":"Brain Behav. Evol."},{"key":"ref_40","first-page":"13","article-title":"Photobiomodulation and vascularization in conduit-based peripheral nerve repair: A narrative review","volume":"42","author":"Fellin","year":"2024","journal-title":"Photobiomodul. Photomed. Laser Surg."},{"key":"ref_41","first-page":"463","article-title":"The effect of delayed photobiomodulation therapy on inferior alveolar nerve recovery after third molar removal: A triple-blinded randomized clinical trial","volume":"42","author":"Yari","year":"2024","journal-title":"Photobiomodul. Photomed. Laser Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13619-024-00215-9","article-title":"Physical modulation and peripheral nerve regeneration: A literature review","volume":"13","author":"Zhai","year":"2024","journal-title":"Cell Regen."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/8\/806\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:22:01Z","timestamp":1786508521000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/8\/806"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cimb48080806"],"URL":"https:\/\/doi.org\/10.3390\/cimb48080806","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]}}}