A review of burn symptoms and potential novel neural targets for non-invasive brain stimulation for treatment of burn sequelae.

Burn survivors experience myriad associated symptoms such as pain, pruritus, fatigue, impaired motor strength, post-traumatic stress, depression, anxiety, and sleep disturbance. Many of these symptoms are common and remain chronic, despite current standard of care. One potential novel intervention to target these post burn symptoms is transcranial direct current stimulation (tDCS). tDCS is a non-invasive brain stimulation (NIBS) technique that modulates neural excitability of a specific target or neural network. The aim of this work is to review the neural circuits of the aforementioned clinical sequelae associated with burn injuries and to provide a scientific rationale for specific NIBS targets that can potentially treat these conditions. We ran a systematic review, following the PRISMA statement, of tDCS effects on burn symptoms. Only three studies matched our criteria. One was a feasibility study assessing cortical plasticity in chronic neuropathic pain following burn injury, one looked at the effects of tDCS to reduce pain anxiety during burn wound care, and one assessed the effects of tDCS to manage pain and pruritus in burn survivors. Current literature on NIBS in burn remains limited, only a few trials have been conducted. Based on our review and results in other populations suffering from similar symptoms as patients with burn injuries, three main areas were selected: the prefrontal region, the parietal area and the motor cortex. Based on the importance of the prefrontal cortex in the emotional component of pain and its implication in various psychosocial symptoms, targeting this region may represent the most promising target. Our review of the neural circuitry involved in post burn symptoms and suggested targeted areas for stimulation provide a spring board for future study initiatives.

Sexual activity and romantic relationships after burn injury: A Life Impact Burn Recovery Evaluation (LIBRE) study.

BACKGROUND: Engaging in healthy sexual activity and romantic relationships are important but often neglected areas of post-burn rehabilitation. The degree to which persons with burn injuries engage in sexual activity and romantic relationships is not well understood. This study examined demographic and clinical characteristics predicting engagement in sexual activity and romantic relationships in a sample of adult burn survivors compared to a general United States sample. METHODS: Data for the adult burn survivor sample were from 601 adult burn survivors who participated in field-testing for the calibration of the Life Impact Burn Recovery Evaluation (LIBRE) Profile, a burn-specific instrument assessing social participation on six scales including sexual activity and romantic relationships. Comparison data were obtained from a general population sample of 2000 adults through sample matching. Demographic predictors of sexual activity and romantic relationship status were examined in each sample using modified Poisson regression analyses. Clinical predictors of engaging in sexual activity and romantic relationships were also examined in the LIBRE sample. RESULTS: Participants were slightly more likely to report being sexually active in the adult burn survivor sample than in the general sample (65% vs. 57%, p < 0.01). There was not a significant difference in romantic relationship status between the two samples (64% vs. 62%, p = 0.31). In multivariable regression analyses, men in both samples were more likely to report being in a sexual relationship (RR in LIBRE sample = 1.23, 95% CI 1.08-1.39; RR in general sample = 1.10, 95% CI 1.02-1.18). Participants in both samples who were not working were less likely to report being sexually active or in a romantic relationship (RRs ranging from 0.73 to 0.83, p < 0.05 for all estimates). In the adult burn survivor sample, respondents with hand burns were more likely to report being sexually active and in a romantic relationship (RR = 1.16, 95% CI 1.01-1.33). Time since burn injury, burn size, and burns to other critical areas were not significantly associated with either outcome in adjusted analyses. CONCLUSIONS: The likelihood of engaging in sexual activity and romantic relationships is similar among adult burn survivors and the comparison group representing a general United States sample of adults. Further research addressing sexual activity and romantic relationships after burn injuries will help to foster better patient-clinician dialogue, pinpoint barriers, design interventions, and allocate appropriate resources.

Longitudinal Clinical Trial Recruitment and Retention Challenges in the Burn Population: Lessons Learned From a Trial Examining a Novel Intervention for Chronic Neuropathic Symptoms.

Long-term trials are key to understanding chronic symptoms such as pain and itch. However, challenges such as high attrition rates and poor recruitment are common when conducting research. The aim of this work was to explore these issues within a long-term randomized control trial using transcranial direct current stimulation to treat pain and itch. This parallel double blinded, placebo-controlled randomized trial was comprised of 15 transcranial direct current stimulation visits and 7 follow-up visits. Participants were over the age of 18, had a burn injury that occurred at least 3 weeks before enrollment, and reported having pain and/or itch that was moderate to severe in intensity. A total of 31 subjects were randomized into either an active or sham transcranial direct current stimulation groups. There were no significant differences between the groups in terms of age, race, education, baseline depression, or anxiety. The median dropout time was at visit 19 (visit 16 [SE = 1.98] for the sham group and visit 19 [SE = 1.98] for the active group). Analysis showed no differences in the dropout rate between groups [χ2(1) = 0.003, P = .954]. The dropout rate was 46.7% for the sham group and 43.8% for the active group. Overall, 45.2% of the subjects dropped out of the trial. Long-term clinical trials are an essential part of evaluating interventions for symptoms such as chronic pain and itch. However, as seen in this trial, long-term studies in the burn population often face recruitment and adherence challenges.

Distinct behavioral response of primary motor cortex stimulation in itch and pain after burn injury.

It is still unclear whether chronic neuropathic pain and itch share similar neural mechanisms. They are two of the most commonly reported challenges following a burn injury and can be some of the most difficult to treat. Transcranial direct current stimulation (tDCS) has previously been studied as a method to modulate pain related neural circuits. Therefore, we aimed to test the effects of tDCS on post-burn neuropathic pain and itch as to understand whether this would induce a simultaneous modulation of these two sensory manifestations. We conducted a pilot randomized controlled clinical trial comprised of two phases of active or sham M1 tDCS (Phase I: 10 sessions followed by a follow-up period of 8 weeks; Phase II: additional 5 sessions followed by a follow-up period of 8 weeks, and a final visit 12 months from baseline). Pain levels were assessed with the Brief Pain Inventory (BPI) and levels of itch severity were assessed with the Visual Analogue Scale (VAS). Measurements were collected at baseline, after the stimulation periods, at 2, 4 and 8-week follow up both for Phase I and II, and at the final visit. Sixteen patients were assigned to the active group and 15 to the sham group. Ten sessions of active tDCS did not reduce the level of pain or itch. We identified that itch levels were reduced at 2-week follow-up after the sham tDCS session, while no placebo effect was found for the active group. No difference between active and sham groups was observed for pain. We did not find any treatment effects during Phase II. Based on these findings, it seems that an important placebo effect occurred during sham tDCS for itch, while active M1 tDCS seems to disrupt sensory compensatory mechanisms. We hypothesize that pain and itch are complementary but distinct mechanisms of adaptation after peripheral sensory injury following a burn injury and need to be treated differently.

Social Interactions and Social Activities After Burn Injury: A Life Impact Burn Recovery Evaluation (LIBRE) Study.

Social interactions and activities are key components of social recovery following burn injuries. The objective of this study is to determine the predictors of these areas of social recovery. This study provides a secondary analysis of a cross-sectional survey of adult burn survivors. The Life Impact Burn Recovery Evaluation-192 was administered to 601 burn survivors for the field-testing of the Life Impact Burn Recovery Evaluation Profile. Survivors aged 18 years and older with injuries ≥5% total BSA or burns to critical areas (hands, feet, face, or genitals) were eligible to participate. Multivariate linear regression analyses were used to determine predictors of the Social Activities and Social Interactions scale scores. A total of 599 people completed the Social Interactions and Social Activities scales. Of these, 77% identified as White Non-Hispanic, 55% were female, 55% were unmarried, and 80% had burns to critical areas. Participants had a mean age of 45 years, a mean time since burn injury of 15 years, and a mean burn size of 41% total BSA. Younger age (P < .01) and being married/living with a significant other (P ≤ .01) were associated with higher Social Activities and Social Interactions scale scores. Individual item responses reveal that survivors had lower scores on items related to participating in outdoor activities (30.4%) or feeling uncomfortable with their appearance (32.4% report dressing to avoid stares). Social interactions and activities are long-term challenges for burn survivors. It is important for clinicians to identify patients who may struggle with social recovery in order to focus on future community-based interventions.