title: Fat Grafting in Burn Scar Alleviates Neuropathic Pain via Anti-Inflammation Effect in Scar and Spinal Cord.
abstract: Burn-induced neuropathic pain is complex, and fat grafting has reportedly improved neuropathic pain. However, the mechanism of fat grafting in improving neuropathic pain is unclear. Previous investigations have found that neuroinflammation causes neuropathic pain, and anti-inflammatory targeting may provide potential therapeutic opportunities in neuropathic pain. We hypothesized that fat grafting in burn scars improves the neuropathic pain through anti-inflammation. Burn-induced scar pain was confirmed using a mechanical response test 4 weeks after burn injuries, and autologous fat grafting in the scar area was performed simultaneously. After 4 weeks, the animals were sacrificed, and specimens were collected for the inflammation test, including COX-2, iNOS, and nNOS in the injured skin and spinal cord dorsal horns through immunohistochemistry and Western assays. Furthermore, pro-inflammatory cytokines (IL-1 β and TNF-α) in the spinal cord were collected. Double immunofluorescent staining images for measuring p-IκB, p-NFκB, p-JNK, and TUNEL as well as Western blots of AKT, Bax/Bcl-2 for the inflammatory process, and apoptosis were analyzed. Fat grafting significantly reduced COX2, nNOS, and iNOS in the skin and spinal cord dorsal horns, as well as IL-1β and TNF-α, compared with the burn group. Moreover, regarding the anti-inflammatory effect, the apoptosis cells in the spinal cord significantly decreased after the fat grafting in the burn injury group. Fat grafting was effective in treating burn-induced neuropathic pain through the alleviation of neuroinflammation and ameliorated spinal neuronal apoptosis.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
authors.forename: Shu-Hung
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Department of Anesthesia, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
authors.forename: Sheng-Hua
authors.initials: SH
authors.lastname: Wu
authors.affiliation: Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
authors.forename: Su-Shin
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
authors.forename: Kao-Ping
authors.initials: KP
authors.lastname: Chang
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
authors.affiliation: Department and Graduate Institute of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
authors.forename: Jwu-Lai
authors.initials: JL
authors.lastname: Yeh
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
authors.forename: Sin-Daw
authors.initials: SD
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
authors.forename: Aij-Lie
authors.initials: AL
authors.lastname: Kwan
authors.affiliation: Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: David Wang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
authors.forename: Chung-Sheng
authors.initials: CS
authors.lastname: Lai
mesh_terms: D000273:Adipose Tissue / Q000637:transplantation*; D000818:Animals; D002056:Burns / Q000601:surgery*; D002921:Cicatrix / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000601:surgery*; D008297:Male; D009415:Nerve Net; D009437:Neuralgia / Q000601:surgery*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology; D016378:Tissue Transplantation; D014182:Transplantation, Autologous
chemical_list: D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2