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Abstract Temporomandibular disorders (TMD) patients can present clinically significant jaw pain fluctuations which can be debilitating and lead to poor global health. The Graded Chronic Pain Scale evaluates pain-related disability and its dichotomous grading (high/low impact pain) can determine patient care pathways and in general high-impact pain patients have worse treatment outcomes. Individuals with low-impact TMD pain are thought to have better psychosocial functioning, more favorable disease course, and better ability to control pain, while individuals with high-impact pain can present with higher levels of physical and psychological symptoms. Thereby, there is reason to believe that individuals with low- and high-impact TMD pain could experience different pain trajectories over time. Our primary objective was to determine if short-term jaw pain fluctuations serve as a clinical marker for the impact status of TMD pain. To this end, we estimated the association between high/low impact pain status and jaw pain fluctuations over three visits (≤ 21-day-period) in 30 TMD cases. Secondarily, we measured the association between jaw pain intensity and pressure pain thresholds (PPT) over the face and hand, the latter measurements compared to matched pain-free controls (n = 17). Jaw pain fluctuations were more frequent among high-impact pain cases (n = 15) than low-impact pain cases (n = 15) (OR 5.5; 95% CI 1.2, 26.4; p value = 0.033). Jaw pain ratings were not associated with PPT ratings (p value > 0.220), suggesting different mechanisms for clinical versus experimental pain. Results from this proof-of-concept study suggest that targeted treatments to reduce short-term pain fluctuations in high-impact TMD pain is a potential strategy to achieve improved patient perception of clinical pain management outcomes.

High-impact temporomandibular disorder (TMD) pain may involve brain mechanisms related to maladaptive central pain modulation. We investigated brain responses to stimulation of trigeminal sites not typically associated with TMD pain by applying noxious dentoalveolar pressure to high- and low-impact TMD pain cases and pain-free controls during functional magnetic resonance imaging (fMRI). Fifty female participants were recruited and assigned to one of three groups based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and Graded Chronic Pain Scale: controls (n = 17), low-impact (n = 17) and high-impact TMD (n = 16). Multimodal whole-brain MRI was acquired following the Human Connectome Project Lifespan protocol, including stimulus-evoked fMRI scans during which painful dentoalveolar pressure was applied to the buccal gingiva of participants. Group analyses were performed using non-parametric permutation tests for parcellated cortical and subcortical neuroimaging data. There were no significant between-group differences for brain activations/deactivations evoked by the noxious dentoalveolar pressure. For individual group mean activations/deactivations, a gradient in the number of parcels surviving thresholding was found according to the TMD pain grade, with the highest number seen in the high-impact group. Among the brain regions activated in chronic TMD pain groups were those previously implicated in sensory-discriminative and motivational-affective pain processing. These results suggest that dentoalveolar pressure pain evokes abnormal brain responses to sensory processing of noxious stimuli in high-impact TMD pain participants, which supports the presence of maladaptive brain plasticity in chronic TMD pain.

Pain assessments typically depend on self-report of the pain experience. Yet, in individuals with autism spectrum disorders, this can be an unreliable due to communication difficulties. Importantly, observations of behavioral hypo- and hyperresponsivity to pain suggest altered pain sensitivity in autism spectrum disorder. Neuroimaging may provide insight into mechanisms underlying pain behaviors. The neural pain signature reliably responds to painful stimulation and is modulated by other outside regions, affecting the pain experience. In this first functional magnetic resonance imaging study of pain in autism spectrum disorder, we investigated neural responses to pain in 15 adults with autism spectrum disorder relative to a typical comparison group (n = 16). We explored temporal and spatial properties of the neural pain signature and its modulators during sustained heat pain. The two groups had indistinguishable pain ratings and neural pain signature responses during acute pain; yet, we observed strikingly reduced neural pain signature response in autism spectrum disorder during sustained pain and after stimulus offset. The posterior cingulate cortex, a neural pain signature modulating region, mirrored this late signal reduction in autism spectrum disorder. Intact early responses, followed by diminished late responses to sustained pain, may reflect altered pain coping or evaluation in autism spectrum disorder. Evidence of a dichotomous neural response to initial versus protracted pain may clarify the coexistence of both hypo- and hyperresponsiveness to pain in autism spectrum disorder.

Elbow fractures comprise 15% of all fractures in children. Our study identifies risk factors and consumer products that contribute to pediatric elbow fractures. The National Electronic Injury Surveillance System was used to collect demographic and consumer product information between 2010 and 2019 for patients younger than 17 years who presented to the emergency department with elbow fractures. Of the 458,433 elbow fractures, the average age of the patients was 7.4 ± 4.1 years and 55.6% were male children. The most common consumer product was sports and recreation equipment, followed by home furnishings. Male patients (P <.0001) and patients 8 years and older (79.2% vs 51.1%, P <.0001) experienced significantly greater rates of injury with sports and recreation equipment. This study evaluates the products associated with pediatric elbow fractures and highlights the importance of safe sports and recreation equipment use and the role of parental counseling in preventing falls from furniture. [ABSTRACT FROM AUTHOR]

Introduction: Lateral condyle fractures are the second most common pediatric elbow fracture. There exist multiple options for internal fixation including buried K-wires, unburied K-wires, and screw fixation. Our study aims to review the current literature and determine if fixation strategy affects outcomes to include fracture union, postoperative range of motion, and need subsequent surgery. Methods: A systematic review of Pubmed, MEDLINE, and EMBASE databases was performed. Included articles involve pediatric patients with displaced lateral condyle fractures treated with internal fixation that reported outcomes to include union rates and complications. Results: Thirteen studies met inclusion criteria for a total of 1299 patients (472 buried K-wires, 717 unburied K-wires, and 110 screws). The patients' average age was 5.8 ± 0.6 years, male (64%), and had 16.3 months of follow-up. No differences in union and infection rates were found. Unburied K-wires had the shortest time to union and the greatest elbow range of motion postoperatively. Conclusions: Our systematic review demonstrates similar outcomes with union and infection rates between all fixation techniques. Unburied K-wires demonstrated a shorter time to union and the greatest postoperative range of motion. Additionally, unburied K-wires may be removed in clinic, decreasing the cost on the healthcare system. Evidence: Level 3. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy of a questionnaire modified for the identification of intraoral pain with neuropathic characteristics in a clinical orofacial pain sample population. Method and Materials: 136 participants with at least one of four orofacial pain diagnoses (temporomandibular disorders [TMD, n = 41], acute dental pain [ADP, n = 41], trigeminal neuralgia [TN, n = 19], persistent dentoalveolar pain disorder [PDAP, n = 14]) and a group of pain-free controls (n = 21) completed the modified S-LANSS, a previously adapted version of the original questionnaire devised to detected patients suffering from intraoral pain with neuropathic characteristics. Psychometric properties (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV]) were calculated in two analyses with two different thresholds: (1) Detection of pain with neuropathic characteristics: PDAP + TN were considered positive, and TMD + ADP + controls were considered negative per gold standard (expert opinion). (2) Detection of PDAP: PDAP was considered positive and TMD + ADP were considered negative per gold standard. For both analyses, target values for adequate sensitivity and specificity were defined as ≥ 80%. Results: For detection of orofacial pain with neuropathic characteristics (PDAP + TN), the modified S-LANSS presented with the most optimistic threshold sensitivity of 52% (95% confidence interval [CI], 34-69), specificity of 70% (95% CI, 60-79), PPV of 35% (95% CI, 22-51), and NPV of 82% (95% CI, 72-89). For detection of PDAP only, with the most optimistic threshold sensitivity was 64% (95% CI, 35-87), specificity 63% (95% CI, 52-74), PPV 23% (95% CI, 11-39) and NPV 91% (95% CI, 81-97). Conclusion: Based on a priori defined criteria, the modified S-LANSS did not show adequate accuracy to detect intraoral pain with neuropathic characteristics in a clinical orofacial pain sample. [ABSTRACT FROM AUTHOR]

Abstract Background Few methods exist to study central nervous system processes following dentoalveolar tactile stimulation using functional magnetic resonance imaging (fMRI), likely due to inherent technical difficulties. Our primary goal was to develop and perform feasibility testing of a novel device capable of delivering valid and reliable dentoalveolar stimuli at dental chair-side and during MRI. Details of a device designed to deliver dentoalveolar dynamic pressure stimuli are described. Device testing took place in three settings: a) laboratory testing to assess range of stimulus force intensities, b) dental chair-side to assess reliability, validity and discriminant ability in force-pain relationship; and c) MRI to evaluate magnetic compatibility and ability to evoke brain activation in painfree subjects similar to those described in the literature. Results A novel device capable of delivering valid and reliable dentoalveolar somatosensory stimulation was developed (ICC = 0.89, 0.78-1 [95% CI]). Psychophysical data analysis showed high discriminant ability in differentiating painfree controls from cases with chronic dentoalveolar pain related to deafferenting dental procedures (sensitivity = 100%, specificity = 86.7%, area under ROC curve = 0.99). FMRI results of dentoalveolar dynamic pressure pain in painfree subjects revealed activation of brain areas typically associated with acute pain processing including thalamus, primary/secondary somatosensory, insular and prefrontal cortex. Conclusions A novel psychophysical method to deliver dynamic dentoalveolar pressure stimulation was developed and validated, allowing non-invasive MRI-based exploration of central nervous system function in response to intraoral somatosensation. Background The organization of the trigeminal system is unique as it provides somatosensory innervation to the face, masticatory and oral structures, the majority of the intracranial contents 1 and to specialized structures (tongue, nasal mucosa, auricle, tympanic membrane, cornea and part of the conjunctiva) 2. Somatic sensory information transmitted by the trigeminal nerve is crucial for normal orofacial function; however, the mechanisms of many chronic pain conditions affecting areas innervated by this sensory system are not well understood 345. The clinical presentation of chronic intraoral pain in the area of a tooth or in a site formally occupied by a tooth with no clinical or radiological signs of pathology, referred to as atypical odontalgia (AO) 67, is one such chronic pain condition of particular interest to dentists that is difficult to diagnose and manage. Recent research suggests both peripheral and central nervous system mechanisms being involved in AO pathophysiology 8910, but the majority of mechanism-based research of patients with AO has focused on the "peripheral aspect" 7. Functional magnetic resonance imaging (fMRI) is an established research technique to study the central aspects of pain 11. Of existing neuroimaging techniques, fMRI provides good spatial resolution of cortical and subcortical structures critical in the processing of nociception, acceptable temporal resolution, does not involve ionizing radiation, and can be performed using most MRI systems that already exist in research centers and the community. For these reasons, we sought to develop a protocol that allows us to use this tool to investigate the central mechanisms involved in the processes of intraoral pain arising from the dentoalveolar region. Using this device, our long-term objective is to improve our understanding of the underlying mechanisms of persistent dentoalveolar pain. In the past few years several studies used fMRI to investigate the human trigeminal system 1213, with a limited subset focusing on intraoral stimulation - specifically on the dentoalveolar processes, such as lip, tongue and teeth stimulation 14 or only teeth 151617. Some reasons for scarce literature on this topic may be the technical challenges involved in delivering facial/intraoral stimulation inside a MR scanner 1718: possibility of magnetic interference, detriment of image quality, subject discomfort and reduced working space between the subject's head and the radiofrequency coil. As a consequence a MR-compatible device would need to not only overcome these challenges but also be capable of delivering a controlled and reproducible stimuli 19, as reliability/reproducibility is a necessary feature of sensory testing 20. Existing MR-compatible methods of dentoalveolar stimulation are limited and do not adequately deliver stimuli across a range of non-painful to painful intensities and/or cannot be adjusted to reach posterior aspects of the dentoalveolar region. Therefore our goal was to develop and test the feasibility of a device able to: 1) provide reliable and valid dentoalveolar stimuli, 2) deliver such stimulation within the restricted space of an MR head coil, 3) be compatible for use within an MR environment, and 4) produce brain activation in painfree controls consistent to those observed by others using fMRI.

Background: The preferred patient-reported outcome measure for the assessment of shoulder conditions continues to evolve. Previous studies correlating the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive tests (CATs) to the American Shoulder and Elbow Surgeons (ASES) score have focused on a singular domain (pain or physical function) but have not evaluated the combined domains of pain and physical function that compose the ASES score. Additionally, previous studies have not provided a multivariable prediction tool to convert PROMIS scores to more familiar legacy scores. Purpose: To establish a valid predictive model of ASES scores using a nonlinear combination of PROMIS domains for physical function and pain. Study Design: Cohort study (Diagnosis); Level of evidence, 3. Methods: The Military Orthopaedics Tracking Injuries and Outcomes Network (MOTION) database is a prospectively collected repository of patient-reported outcomes and intraoperative variables. Patients in MOTION research who underwent shoulder surgery and completed the ASES, PROMIS Physical Function, and PROMIS Pain Interference at varying time points were included in the present analysis. Nonlinear multivariable predictive models were created to establish an ASES index score and then validated using "leave 1 out" techniques and minimal clinically important difference /substantial clinical benefit (MCID/SCB) analysis. Results: A total of 909 patients completed the ASES, PROMIS Physical Function, and PROMIS Pain Interference at presurgery, 6 weeks, 6 months, and 1 year after surgery, providing 1502 complete observations. The PROMIS CAT predictive model was strongly validated to predict the ASES (Pearson coefficient = 0.76-0.78; R 2 = 0.57-0.62; root mean square error = 13.3-14.1). The MCID/SCB for the ASES was 21.7, and the best ASES index MCID/SCB was 19.4, suggesting that the derived ASES index is effective and can reliably re-create ASES scores. Conclusion: The PROMIS CAT predictive models are able to approximate the ASES score within 13 to 14 points, which is 7 points more accurate than the ASES MCID/SCB derived from the sample. Our ASES index algorithm, which is freely available online (https://osf.io/ctmnd/), has a lower MCID/SCB than the ASES itself. This algorithm can be used to decrease patient survey burden by 11 questions and provide a reliable ASES analog to clinicians. [ABSTRACT FROM AUTHOR]

Chronic overlapping pain conditions (COPCs) are conditions that share several clinical characteristics and symptomatology, are usually considered idiopathic in nature, and are frequently comorbid. Currently, there are no established inclusion criteria to determine which conditions should be included under this umbrella term despite different systems proposed. Persistent dentoalveolar pain disorder (PDAP), also referred to as atypical odontalgia and thought to be a component of persistent idiopathic facial pain, is a chronic pain condition that manifests as a persistent tooth pain or pain over a dentoalveolar site formerly occupied by a tooth in the absence of detectable pathology during clinical or radiological examination. PDAP is considered idiopathic in nature, and its pathophysiological mechanisms are not fully understood. Our objective was to investigate whether PDAP fits the conceptual paradigm of COPC given its characteristics and commonalities with other COPC, based on published literature identified through a scoping review. We found that PDAP fits 16 out of 18 common characteristics among COPCs, and based on this finding, we discuss the implications of PDAP being considered a COPC. [ABSTRACT FROM AUTHOR]

Summary: Background: Endogenous pain modulation (EPM) reflects the brain's ability to modulate incoming nociceptive inputs, and deficient EPM was implicated as a chronic pain mechanism. EPM status has been investigated in temporomandibular disorders (TMD) patients with conflicting results, and its relationship with clinical characteristics in this population is not well known. Objectives: (a) Determine EPM responses in chronic TMD cases and pain‐free controls; (b) Derive pain modulation profiles (PMP) based on individual EPM responses; and (c) Categorise clinical characteristics of TMD cases and pain‐free controls based on their individual PMP. Methods: Twenty‐two chronic TMD cases and 17 age‐matched pain‐free controls, all females, were comprehensively characterised regarding clinical characteristics and underwent EPM testing using temporal summation of pain (TSP) and conditioned pain modulation (CPM) protocols over the face and hand. Individuals were categorised into PMPs (I‐IV) based on predetermined cut‐off points for TSP and CPM responses. Results: Between‐group comparisons showed similar TSP and CPM responses (P > 0.23) in the face, while TMD cases showed significantly increased TSP (P = 0.04) but similar CPM responses (P > 0.17) in the hand relative to controls. Similar distribution across PMPs and clinical characteristics when categorised into PMPs was found for both groups. Body mass index was associated with increased TSP and reduced CPM in the face in TMD cases. Conclusion: Endogenous pain modulation responses over the face were similar between groups. TMD cases showed increased hand TSP compared to controls while both groups showed no significant hand CPM. PMP classification showed similar results between groups, and further refinement of PMP determination is warranted. [ABSTRACT FROM AUTHOR]

Aims: (1) To determine the brain regions activated by dentoalveolar pressure stimulation in persistent dentoalveolar pain disorder (PDAP) patients, and (2) to compare these activation patterns to those seen in pain-free control subjects. Methods: A total of 13 PDAP patients and 13 matched controls completed the study. Clinical pain characteristics and psychosocial data were collected. Dentoalveolar mechanical pain thresholds were determined with a custom-made device over the painful area for patients and were used as the stimulation level during functional magnetic resonance imaging (fMRI) data acquisition. Control subjects received two stimulation levels over matched locations during fMRI scanning: one determined (as above) that evoked equally subjective pain ratings matching those of patients (subjective-pain match) and another nonpainful stimulation level matching the average stimulus intensity provided to patients (stimulus-intensity match). Clinical and psychosocial data were analyzed using independent samples t tests, Mann-Whitney U test, and Spearman rank-order correlation coefficient. fMRI data were analyzed using validated neuroimaging software and tested using a general linear model. Results: PDAP patients had greater anxiety (P < .0001) and depression scores (P = .001), more jaw function impairment (P < .0001), and greater social impact (P < .0001) than controls. No significant differences were found for brain activation spatial extent (PDAP X Controls subjective pain: P = .48; PDAP X Controls stimulus intensity: P = .12). Brain activations were significantly increased for PDAP patients compared to control subjects when matched to stimulus intensity in several regions related to the sensory-discriminative and cognitive components of pain perception, including the primary and secondary somatosensory cortices, inferior parietal lobule, insula, premotor cortex, prefrontal cortex, and thalamus. When matched to subjective pain ratings, increased brain activations were still present for PDAP patients compared to controls, although to a lesser extent. Conclusion: The present results suggest that dentoalveolar pressure is processed differently in the brain of PDAP patients, and the increased activation in several brain areas is consistent with amplified pain processing. [ABSTRACT FROM AUTHOR]

Deciphering the initial steps of SARS-CoV-2 infection, that influence COVID-19 outcomes, is challenging because animal models do not always reproduce human biological processes and in vitro systems do not recapitulate the histoarchitecture and cellular composition of respiratory tissues. To address this, we developed an innovative ex vivo model of whole human lung infection with SARS-CoV-2, leveraging a lung transplantation technique. Through single-cell RNA-seq, we identified that alveolar and monocyte-derived macrophages (AMs and MoMacs) were initial targets of the virus. Exposure of isolated lung AMs, MoMacs, classical monocytes and non-classical monocytes (ncMos) to SARS-CoV-2 variants revealed that while all subsets responded, MoMacs produced higher levels of inflammatory cytokines than AMs, and ncMos contributed the least. A Wuhan lineage appeared to be more potent than a D614G virus, in a dose-dependent manner. Amidst the ambiguity in the literature regarding the initial SARS-CoV-2 cell target, our study reveals that AMs and MoMacs are dominant primary entry points for the virus, and suggests that their responses may conduct subsequent injury, depending on their abundance, the viral strain and dose. Interfering on virus interaction with lung macrophages should be considered in prophylactic strategies., (© 2024. The Author(s).)

Ex-vivo lung perfusion (EVLP) has extended the number of transplantable lungs by reconditioning marginal organs. However, EVLP is performed at 37°C without homeostatic regulation leading to metabolic wastes' accumulation in the perfusate and, as a corrective measure, the costly perfusate is repeatedly replaced during the standard of care procedure. As an interesting alternative, a hemodialyzer could be placed on the EVLP circuit, which was previously shown to rebalance the perfusate composition and to maintain lung function and viability without appearing to impact the global gene expression in the lung. Here, we assessed the biological effects of a hemodialyzer during EVLP by performing biochemical and refined functional genomic analyses over a 12h procedure in a pig model. We found that dialysis stabilized electrolytic and metabolic parameters of the perfusate but enhanced the gene expression and protein accumulation of several inflammatory cytokines and promoted a genomic profile predicting higher endothelial activation already at 6h and higher immune cytokine signaling at 12h. Therefore, epuration of EVLP with a dialyzer, while correcting features of the perfusate composition and maintaining the respiratory function, promotes inflammatory responses in the tissue. This finding suggests that modifying the metabolite composition of the perfusate by dialysis during EVLP can have detrimental effects on the tissue response and that this strategy should not be transferred as such to the clinic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 De Wolf, Gouin, Jouneau, Glorion, Premachandra, Pascale, Huriet, Estephan, Leplat, Egidy, Richard, Gelin, Urien, Roux, Le Guen, Schwartz-Cornil and Sage.)

Children with cerebral palsy (CP) and those with avascular necosis (AVN) after treatment of developmental hip dysplasia (DDH) are at risk of developing coxa valga. Proximal femur guided growth is a minimally invasive option to correct this deformity. A systematic review of articles that described treatment of coxa valga with proximal femur guided growth (PFGG) and reporting on primary radiographic outcomes, demographic variables, surgical variables and complications. One hundred and seventy-nine hips underwent PFGG (117 with CP and 62 with lateral overgrowth). Average age at surgery was 8.1 years; average follow-up was 52.5 months. Migration percentage improved from 11.2% (p < 0.0001). Neck-shaft angle improved by 11.9° (p < 0.0001). The most common complication was screw growth out of the physis (30% of cases). PFGG can correct coxa valga, improve radiographic parameters, and in children with CP prevent further subluxation. This technique modulates proximal femur growth, induces changes to the acetabulum and can correct valgus deformity. Evidence Level III. (Journal of Surgical Orthopaedic Advances 32(4):049-052, 2024).

Abstract: The most recent prevalence estimate of post-traumatic headache (PTH) after traumatic brain injury (TBI) in veterans and civilians dates back to 2008. The prevalence was found to be 57.8%, with surprising higher rates (75.3%) in mild TBI when compared with those with moderate/severe TBI (32.1%). However, the revision of mild TBI diagnostic criteria and an historic peak of TBI in the elderly individuals attributed to the ageing population may lead to different results. Thus, we conducted a systematic review and meta-analysis to assess the updated prevalence of PTH during the past 14 years only in civilians. A literature search was conducted following PRISMA guidelines guided by a librarian. Screening, full-text assessment, data extraction, and risk of bias assessment were performed blindly by 2 raters. Meta-analysis of proportions using the Freeman and Tukey double arcsine method of transformation was conducted. Heterogeneity, sensitivity analysis, and meta-regressions were performed with the predictors: year of publication, mean age, sex, TBI severity, and study design. Sixteen studies were selected for the qualitative analysis and 10 for the meta-analysis. The overall prevalence estimate of PTH was 47.1%, (confidence interval = 34.6, 59.8, prediction intervals = 10.8, 85.4), being similar at different time points (3, 6, 12, and 36+ months). Heterogeneity was high, and none of the meta-regressions were significant. The overall prevalence of PTH after TBI over the past 14 years remains high even if assessed only in civilians. However, the prevalence rates attributed to mild and moderate/severe TBI were similar, differing significantly from previous reports. Efforts are needed to improve TBI outcomes., (Copyright © 2023 International Association for the Study of Pain.)