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Hypertrophic Scar Severity at Autograft Sites Is Associated With Increased Pain and Itch After Major Thermal Burn Injury.

ABSTRACT: Approximately three quarters of major thermal burn injury (MThBI) survivors suffer from hypertrophic scarring (HTS) and over half experience chronic pain or itch. In survivors of MThBI, HTS and chronic pain or itch are considered one of the greatest unmet challenges of postburn injury care and psychosocial reintegration. Although scarring, itch, and pain have been clinically associated, there are no prospective, multisite studies examining tissue autograft site pain or itch and scar outcomes. The authors collected a representative cohort (n = 56) of MThBI survivors who received autografting within 14 days of injury and evaluated graft-site pain or itch severity (0-10 Numeric Rating Scale) and HTS using a validated scar photograph assessment scale 6 months following MThBI. Given that stress is known to influence wound healing, the authors also assessed the relationship between previous trauma exposure, peritraumatic stress, preburn overall health (SF-12), scarring, and chronic pain or itch severity using Spearman's correlation. Association between HTS and chronic pain or itch was significant in a linear regression model adjusted for age, sex, and ethnicity (β = 0.2, P = .033 for pain, β = 0.2, P = .019 for itch). Results indicate that prior trauma exposure is inversely correlated (r = -.363, P = .030) with scar severity, but not pain or itch severity 6 months after MThBI. Study results suggest that preburn chronic pain or itch is associated with pathological scarring 6 months following MThBI. Results also indicate that stress may improve scarring after MThBI. Further work to understand the mechanisms that underlie both HTS and chronic pain or itch and their relationship to chronic stress is critical to the development of novel therapies to assist burn survivors recover.

SUBMITTER: Mauck MC

PROVIDER: S-EPMC7189975 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: As a fibrotic disease with a high incidence, the pathogenesis of hypertrophic scarring is still not fully understood, and the treatment of this disease is also challenging. In recent years, human adipose-derived mesenchymal stem cells (AD-MSCs) have been considered an effective treatment for hypertrophic scars. This study mainly explored whether the therapeutic effect of AD-MSCs on hypertrophic scars is associated with oxidative-stress-related proteins. Methods: AD-MSCs were isolated from adipose tissues and characterized through flow cytometry and a differentiation test. Afterwards, coculture, cell proliferation, apoptosis, and migration were detected. Western blotting and a quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect oxidative stress-related genes and protein expression in hypertrophic scar fibroblasts (HSFs). Flow cytometry was used to detect reactive oxygen species (ROS). A nude mouse animal model was established; the effect of AD-MSCs on hypertrophic scars was observed; and hematoxylin and eosin staining, Masson's staining, and immunofluorescence staining were performed. Furthermore, the content of oxidative-stress-related proteins, including nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), B-cell lymphoma 2(Bcl2), Bcl2-associated X(BAX) and caspase 3, was detected. Results: Our results showed that AD-MSCs inhibited HSFs' proliferation and migration and promoted apoptosis. Moreover, after coculture, the expression of antioxidant enzymes, including HO-1, in HSFs decreased; the content of reactive oxygen species increased; and the expression of Nrf2 decreased significantly. In animal experiments, we found that, at 14 days after injection of AD-MSCs into human hypertrophic scar tissue blocks that were transplanted onto the dorsum of nude mice, the weight of the tissue blocks decreased significantly. Hematoxylin and eosin staining and Masson's staining demonstrated a rearrangement of collagen fibers. We also found that Nrf2 and antioxidant enzymes decreased significantly, while apoptotic cells increased after AD-MSC treatment. Conclusions: Our results demonstrated that AD-MSCs efficiently cured hypertrophic scars by promoting the apoptosis of HSFs and by inhibiting their proliferation and migration, which may be related to the inhibition of Nrf2 expression in HSFs, suggesting that AD-MSCs may provide an alternative therapeutic approach for the treatment of hypertrophic scars.

Project description:ObjectiveThe aim of the study was to determine the longitudinal validity, reproducibility, responsiveness and interpretability of the adult version of the Brisbane Burn Scar Impact Profile, a patient-report measure of health-related quality of life.MethodsA prospective longitudinal cohort study of patients with or at risk of burn scarring was conducted at three assessment points (at baseline around the time of wound healing, one to two weeks post-baseline and 1-month post-baseline). Participants attending a major metropolitan adult burn centre at baseline were recruited. Participants completed the Brisbane Burn Scar Impact Profile and the 36-item Short Form Health Survey and Patient Observer Scar Assessment Scale. Intraclass Correlation Coefficients (ICCs), smallest detectable change, percentage of those who improved, stayed the same or worsened and Area under the Receiver Operating Characteristic Curve (AUC) were used to test the aim.ResultsData were included for 118 participants at baseline, 68 participants at one to two weeks and 57 participants at 1-month post-baseline. All groups of items had acceptable reproducibility, except for the overall impact of burn scars (ICC = 0.69), the impact of sensations which was not expected to be stable (ICC = 0.63), mobility and daily activities (ICC = 0.63, 0.67 respectively). The responsiveness of six out of seven groups of items able to be tested against external criterion was supported (AUC = 0.72-0.75). Hypothesised correlations of changes in the Brisbane Burn Scar Impact Profile items with changes in criterion measures generally supported longitudinal validity (e.g., nine out of thirteen hypotheses using the SF-36 as an external criterion were supported). Internal consistency estimates, item-total and inter-item correlations indicated there was likely redundancy of some groups of items, particularly in the relationships and social interaction, appearance and emotional reactions items (Chronbach's alpha range = 0.94-0.95).ConclusionSupport was found for the reproducibility, longitudinal validity, responsiveness and interpretability of most groups of Brisbane Burn Scar Impact Profile items and some individual items in the test population. Potential redundancy of items should be investigated further.

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Hypertrophic Scar Severity at Autograft Sites Is Associated With Increased Pain and Itch After Major Thermal Burn Injury.

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