Background A major potential goal of burn therapy is to limit progression of partial to full-thickness) burns. To better test therapies, we developed and validated a vertical progression porcine burn model in which partial thickness burns treated with an occlusive dressing convert to full thickness burns that heal with scarring and wound contraction. Methods Forty contact burns were created on the backs and flanks of two young swine using a 150 gm aluminum bar preheated to 70°, 80°, or 90°Celsius for 20 or 30 seconds. The necrotic epidermis was removed and the burns were covered with a polyurethane occlusive dressing. Burns were photographed at 1, 24, and 48 hours as well as at 7, 14, 21, and 28 days post injury. Full thickness biopsies were obtained at 1, 4, 24, and 48 hours, as well as at 7 and 28 days. The primary outcomes were presence of deep contracted scars and wound area 28 days after injury. Secondary outcomes were depth of injury, reepithelialization, and depth of scars. Data were compared across burn conditions using ANOVA and χ2 tests. Results Eight replicate burns were created with the aluminum bar using the following temperature/contact-time combinations: 70/20, 70/30, 80/20, 80/30, and 90/20. The percentage of burns healing with contracted scars were 70/20–0%, 70/30–25%, 80/20–50%, 80/30–75%, and 90/20–100% (P=0.05). Wound areas at 28 days by injury conditions were 70/20–8.1 cm2, 70/30–7.8 cm2, 80/20–6.6 cm2, 80/30–4.9 cm2, and 90/20–4.8 cm2 (P=0.007). Depth of injury judged by depth of endothelial damage for the 80/20 and 80/30 burns at 1 hr was 36% and 60% of the dermal thickness respectively. The depth of injury to the endothelial cells 1 hour after injury was inversely correlated with the degree of scar area (Pearson’s correlation r=−0.71, P<0.001). Conclusions Exposure of porcine skin to an aluminum bar preheated to 80°C for 20 or 30 seconds results initially in a partial thickness burn that when treated with an occlusive dressing progresses to a full thickness injury and heals with significant scarring and wound contracture.

Pain perception can be powerfully influenced by an individual's expectations and beliefs. Although the cortical circuitry responsible for pain modulation has been thoroughly investigated, the brainstem pathways involved in the modulatory phenomena of placebo analgesia and nocebo hyperalgesia remain to be directly addressed. This study used ultra-high-field 7 tesla functional MRI (fMRI) to accurately resolve differences in brainstem circuitry present during the generation of placebo analgesia and nocebo hyperalgesia in healthy human participants (N = 25, 12 male). Over 2 successive days, through blinded application of altered thermal stimuli, participants were deceptively conditioned to believe that two inert creams labeled lidocaine (placebo) and capsaicin (nocebo) were acting to modulate their pain relative to a third Vaseline (control) cream. In a subsequent test phase, fMRI image sets were collected while participants were given identical noxious stimuli to all three cream sites. Pain intensity ratings were collected and placebo and nocebo responses determined. Brainstem-specific fMRI analysis revealed altered activity in key pain modulatory nuclei, including a disparate recruitment of the periaqueductal gray (PAG)-rostral ventromedial medulla (RVM) pathway when both greater placebo and nocebo effects were observed. Additionally, we found that placebo and nocebo responses differentially activated the parabrachial nucleus but overlapped in engagement of the substantia nigra and locus coeruleus. These data reveal that placebo and nocebo effects are generated through differential engagement of the PAG-RVM pathway, which in concert with other brainstem sites likely influences the experience of pain by modulating activity at the level of the dorsal horn.

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For over a century, neuroscientists have been working toward parcellating the human cortex into distinct neurobiological regions. Modern technologies offer many parcellation methods for healthy cortices acquired through magnetic resonance imaging. However, these methods are suboptimal for personalized neurosurgical application given that pathology and resection distort the cerebrum. We sought to overcome this problem by developing a novel connectivity-based parcellation approach that can be applied at the single-subject level. Utilizing normative diffusion data, we first developed a machine-learning (ML) classifier to learn the typical structural connectivity patterns of healthy subjects. Specifically, the Glasser HCP atlas was utilized as a prior to calculate the streamline connectivity between each voxel and each parcel of the atlas. Using the resultant feature vector, we determined the parcel identity of each voxel in neurosurgical patients (n = 40) and thereby iteratively adjusted the prior. This approach enabled us to create patient-specific maps independent of brain shape and pathological distortion. The supervised ML classifier reparcellated an average of 2.65% of cortical voxels across a healthy dataset (n = 178) and an average of 5.5% in neurosurgical patients. Our patient dataset consisted of subjects with supratentorial infiltrating gliomas operated on by the senior author who then assessed the validity and practical utility of the re-parcellated diffusion data. We demonstrate a rapid and effective ML parcellation approach to parcellation of the human cortex during anatomical distortion. Our approach overcomes limitations of indiscriminately applying atlas-based registration from healthy subjects by employing a voxel-wise connectivity approach based on individual data.

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