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Abstract: Developmental trajectories for neck disability after whiplash injury have been identified. Their relationship to cold and mechanical sensitivity trajectories is not known. We aimed to (1) identify recovery trajectories of cold and mechanical sensitivity, (2) explore their codevelopment with disability trajectories, (3) identify predictors of sensitivity trajectories, and (4) explore codevelopment of cold and mechanical sensitivity trajectories. Participants (n = 233) were assessed at <1, 3, 6, and 12 months after whiplash injury. Outcomes were cold pain detection threshold (CPT at neck), pressure pain detection thresholds (PPT, neck C5, and tibialis anterior), and the Neck Disability Index. We used group-based trajectory models to identify postinjury recovery trajectories and multinominal logistic regression to explore associations between baseline characteristics and trajectory membership. We identified the following trajectory groups: CPT (low [50.0%], moderate [29.7%], and high [20.4%] sensitivity); PPT C5 (low [10.8%] and high [89.2%] sensitivity); and PPT tibialis anterior (low [23.9%], moderate [39.0%], and high [37.1%] sensitivity); all were stable over the 12 months. There was good correspondence between disability and cold sensitivity trajectory groups but not for mechanical sensitivity; cold and mechanical sensitivity trajectories were not well associated. Higher baseline pain predicted membership of the high cold sensitivity trajectory (RR 1.27, 95% CI 1.01-1.59) and hyperarousal symptoms predicted membership of the moderate cold sensitivity trajectory (RR 1.17, 95% CI 1.01-1.36). We found no associations between baseline characteristics and mechanical sensitivity. There is an interplay between cold allodynia, pain, and hyperarousal symptoms in development of ongoing disability after whiplash injury. Different mechanisms likely underlie cold and mechanical sensitivity., (Copyright © 2024 International Association for the Study of Pain.)

Insufficient and deficient vitamin D may be associated with chronic musculoskeletal pain, but study findings are conflicting, and few account for important confounding factors. This cross-sectional study explored the association between serum vitamin D status and chronic musculoskeletal pain in various body sites, adjusting for a wide range and a number of potential confounding factors. Data collected at the baseline assessments of 349,221 UK Biobank participants between 2006 and 2010 were analyzed. Serum 25-hydroxyvitamin D was measured and categorized as <25.0 nmol/L (severe deficiency), 25.0 to 49.9 nmol/L (deficiency), 50.0 to 74.9 nmol/L (insufficiency), and ≥75.0 nmol/L (sufficiency). The outcome was self-reported chronic musculoskeletal pain at any site, neck/shoulder, back, hip, knee, or widespread pain that interfered with usual activities. Potential confounders were identified using directed acyclic graphs and included sociodemographic, lifestyle, psychological factors, and medical comorbidities. Simple models adjusted for age and sex showed significant associations between suboptimal vitamin D status and chronic pain across all sites (odds ratios [ORs] ranged 1.07-2.85). These associations were weakened or became insignificant after accounting for all confounding factors (ORs ≤ 1.01) for chronic regional musculoskeletal pain. Severe vitamin D deficiency remained a significant and positive association with chronic widespread pain after adjusting for all confounding factors (OR [95% confidence interval]: 1.26 [1.07, 1.49]). This study suggests that, while vitamin D status is not a key independent determinant of chronic regional musculoskeletal pain, severe vitamin D deficiency may be associated with chronic widespread pain. PERSPECTIVE: After accounting for various confounders, vitamin D deficiency was not associated with regional musculoskeletal pain. However, the relationship between chronic widespread pain severe vitamin D deficiency remained after confounder adjustment. Use of vitamin D supplements in individuals with chronic widespread pain and severe vitamin D deficiency warrants further exploration., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Inflammation is linked with chronic pain but the extent to which this relationship is associated with biopsychosocial factors is not known. We investigated relationships between blood C-reactive protein (CRP) and regional chronic pain conditions adjusting for a large range and number of potential confounders. We performed cross-sectional analyses using the UK Biobank (N = 415,567) comparing CRP in people reporting any of 9 types of regional chronic pain with pain-free controls. Using logistic regression modelling, we explored relationships between CRP and the presence of chronic pain, with demographic, socioeconomic, psychological/lifestyle factors, and medical comorbidities as covariates. CRP was higher in chronic pain at any site compared with controls (Females: median [interquartile range] 1.60 mg/L [2.74] vs 1.17 mg/L [1.87], P < .001; Males: 1.44 mg/L [2.12] vs 1.15 mg/L [1.65], P < .001). In males, associations between CRP and all types of chronic pain were attenuated but remained significant after adjustment for biopsychosocial covariates (OR range 1.08-1.49, P ≤ .001). For females, adjusted associations between CRP and pain remained significant for most chronic pain types (OR range 1.07-1.34, P < .001) except for facial pain (OR 1.04, P = .17) and headache (OR 1.02, P = .07)-although these non-significant findings may reflect reduced sample size. The significant association between CRP and chronic pain after adjustment for key biopsychosocial confounders implicates an independent underlying biological mechanism of inflammation in chronic pain. The presence of yet unknown or unmeasured confounding factors cannot be ruled out. Our findings may inform better-targeted treatments for chronic pain. PERSPECTIVE: Using a large-scale dataset, this article investigates associations between chronic pain conditions and blood C-reactive protein (CRP), to evaluate the confounding effects of a range of biopsychosocial factors. CRP levels were higher in those with chronic pain versus controls after adjusting for confounders-suggesting a possible independent biological mechanism., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Poor sleep is thought to enhance pain via increasing peripheral and/or central sensitization. Aerobic exercise, conversely, relives pain via reducing sensitization, among other mechanisms. This raises two clinical questions: (1) does poor sleep contribute to the transition from acute-to-persistent pain, and (2) can exercise protect against this transition? This study tested these questions and explored underlying mechanisms in a controlled injury model. Twenty-nine adult female Sprague-Dawley rats performed an intensive lever-pulling task for 4 weeks to induce symptoms consistent with clinical acute-onset overuse injury. Rats were then divided into three groups and exposed for 4 weeks to either: voluntary exercise via access to a running wheel, sleep disturbance, or both. Pain-related behaviours (forepaw mechanical sensitivity, reflexive grip strength), systemic levels of brain derived neurotrophic factor (BDNF), estradiol and corticosterone, and white blood cells (WBC) were assessed pre-injury, post-injury and post-intervention. Mechanical sensitivity increased post-injury and remained elevated with sleep disturbance alone, but decreased to pre-injury levels with exercise both with and without sleep disturbance. Reflexive grip strength decreased post-injury but recovered post-intervention-more with exercise than sleep disturbance. BDNF increased with sleep disturbance alone, remained at pre-injury levels with exercise regardless of sleep, and correlated with mechanical sensitivity. WBCs and estradiol increased with exercise alone and together with sleep disturbance, respectively. Corticosterone was not impacted by injury/intervention. Findings provide preliminary evidence for a role of poor sleep in the transition from acute-to-persistent pain, and the potential for aerobic exercise to counter these effects. BDNF might have a role in these relationships., Competing Interests: No conflict of interest for all authors., (© 2023 The Authors.)

Purpose: Causal mechanisms underlying systemic inflammation in spinal & widespread pain remain an intractable experimental challenge. Here we examined whether: (i) associations between blood C-reactive protein (CRP) and chronic back, neck/shoulder & widespread pain can be explained by shared underlying genetic variants; and (ii) higher CRP levels causally contribute to these conditions., Methods: Using genome-wide association studies (GWAS) of chronic back, neck/shoulder & widespread pain (N = 6063-79,089 cases; N = 239,125 controls) and GWAS summary statistics for blood CRP (Pan-UK Biobank N = 400,094 & PAGE consortium N = 28,520), we employed cross-trait bivariate linkage disequilibrium score regression to determine genetic correlations (rG) between these chronic pain phenotypes and CRP levels (FDR < 5%). Latent causal variable (LCV) and generalised summary data-based Mendelian randomisation (GSMR) analyses examined putative causal associations between chronic pain & CRP (FDR < 5%)., Results: Higher CRP levels were genetically correlated with chronic back, neck/shoulder & widespread pain (rG range 0.26-0.36; P ≤ 8.07E-9; 3/6 trait pairs). Although genetic causal proportions (GCP) did not explain this finding (GCP range - 0.32-0.08; P ≥ 0.02), GSMR demonstrated putative causal effects of higher CRP levels contributing to each pain type (beta range 0.027-0.166; P ≤ 9.82E-03; 3 trait pairs) as well as neck/shoulder pain effects on CRP levels (beta [S.E.] 0.030 [0.021]; P = 6.97E-04)., Conclusion: This genetic evidence for higher CRP levels in chronic spinal (back, neck/shoulder) & widespread pain warrants further large-scale multimodal & prospective longitudinal studies to accelerate the identification of novel translational targets and more effective therapeutic strategies., (© 2023. The Author(s).)

Physiotherapists are increasingly using psychological treatments for musculoskeletal conditions. We assessed the effects of physiotherapist-delivered psychological interventions on pain, disability, and quality of life in neck pain. We evaluated quality of intervention reporting. We searched databases for randomized controlled trials (RCTs) comprising individuals with acute or chronic whiplash-associated disorder (WAD) or nontraumatic neck pain (NTNP), comparing physiotherapist-delivered psychological interventions to standard care or no treatment. Data were extracted regarding study characteristics and outcomes. Standardised mean difference (SMD) was calculated by random-effects meta-analysis. We evaluated certainty of evidence using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) and intervention reporting using TIDieR. Fourteen RCTs (18 articles-4 detail additional outcome/follow-up data) were included comprising 2028 patients, examining acute WAD (n = 4), subacute/mixed NTNP (n = 3), chronic WAD (n = 2), and chronic NTNP (n = 5). Treatment effects on pain favoured psychological interventions in chronic NTNP at short-term (SMD -0.40 [95% CI -0.73, -0.07]), medium-term (SMD -0.29 [95% CI -0.57, 0.00]), and long-term (SMD -0.32 [95% CI -0.60, -0.05]) follow-up. For disability, effects favoured psychological interventions in acute WAD at short-term follow-up (SMD -0.39 [95% CI -0.72, -0.07]) and chronic NTNP at short-term (SMD -0.53 [95% CI -0.91, -0.15]), medium-term (SMD -0.49 [95% CI -0.77, -0.21]), and long-term (SMD -0.60 [95% CI -0.94, -0.26]) follow-up. GRADE ratings were typically moderate, and intervention reporting often lacked provision of trial materials and procedural descriptions. Psychological interventions delivered by physiotherapists were more effective than standard physiotherapy for chronic NTNP (small-to-medium effects) and, in the short term, acute WAD., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

The multiple comorbidities & dimensions of chronic pain present a formidable challenge in disentangling its aetiology. Here, we performed genome-wide association studies of 8 chronic pain types using UK Biobank data (N =4,037-79,089 cases; N = 239,125 controls), followed by bivariate linkage disequilibrium-score regression and latent causal variable analyses to determine (respectively) their genetic correlations and genetic causal proportion (GCP) parameters with 1,492 other complex traits. We report evidence of a shared genetic signature across chronic pain types as their genetic correlations and GCP directions were broadly consistent across an array of biopsychosocial traits. Across 5,942 significant genetic correlations, 570 trait pairs could be explained by a causal association (|GCP| >0.6; 5% false discovery rate), including 82 traits affected by pain while 410 contributed to an increased risk of chronic pain (cf. 78 with a decreased risk) such as certain somatic pathologies (eg, musculoskeletal), psychiatric traits (eg, depression), socioeconomic factors (eg, occupation) and medical comorbidities (eg, cardiovascular disease). This data-driven phenome-wide association analysis has demonstrated a novel and efficient strategy for identifying genetically supported risk & protective traits to enhance the design of interventional trials targeting underlying causal factors and accelerate the development of more effective treatments with broader clinical utility. PERSPECTIVE: Through large-scale phenome-wide association analyses of >1,400 biopsychosocial traits, this article provides evidence for a shared genetic signature across 8 common chronic pain types. It lays the foundation for further translational studies focused on identifying causal genetic variants and pathophysiological pathways to develop novel diagnostic & therapeutic technologies and strategies., (Copyright © 2022 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Autonomic nervous system dysfunction has been implicated in chronic whiplash-associated disorder (WAD). However, the relationship between autonomic variables (e.g., resting heart rate and blood pressure) and clinical factors in chronic WAD is not well understood. This study sought to examine the associations between resting heart rate, resting blood pressure, pain processing and psychological variables in chronic WAD and in pain-free controls., Design: Secondary analysis of a cross-sectional study., Setting: University clinical research laboratory., Subjects: Thirty-six people with chronic WAD Grade II (mean [SD] age 40.1 [14.6] years, 28 females) and 25 pain-free controls (35.6 [13.0] years, 17 females)., Methods: Participants had resting heart rate, systolic and diastolic blood pressure measured. Pain processing measures comprised: (i) pain pressure threshold at the cervical spine, hand and leg, (ii) temporal summation at the cervical spine and hand, and (iii) conditioned pain modulation. Psychological outcomes included measures of kinesiophobia, pain catastrophizing and post-traumatic stress symptoms. Correlations between autonomic variables, pain processing and psychological variables were determined (P &lt; .05, 5% FDR)., Results: No significant correlations between autonomic and pain processing variables, or autonomic and psychological variables were found in the chronic WAD group. In the control group, diastolic blood pressure was positively correlated with cervical spine pressure pain threshold (r = 0.53, P = .007)., Conclusions: An association between blood pressure and pain sensitivity was observed in the control group but not the chronic WAD group. Such an association appears to be disrupted in chronic WAD, which may infer involvement of autonomic pathways in the pathophysiology of this condition., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Background: Incarcerated populations experience an elevated prevalence of opioid use disorder (OUD). Federal correctional institutions in Canada have increasingly treated OUD among correctional populations via opioid agonist treatment (OAT) - an evidence based pharmacotherapy that works to reduce drug use and related health harms. However, there is limited evidence regarding incarcerated individuals' experiences with institutional-based OAT, as well potential OAT-related community release prospects. This information is important for optimal treatment retention and improved health. To address this knowledge gap, we conducted a longitudinal follow-up study examining OAT-related experiences among federally incarcerated individuals before and after community release. This article focuses on the baseline (pre-release) data., Methods: This mixed-methods study examined OAT-related experiences and release prospects among n = 46 individuals scheduled for community release, recruited from seven federal prisons located in Ontario, Canada. Participants underwent a comprehensive interviewer-administered on-site assessment, including quantitative and qualitative items. Assessment data was furthermore linked to administrative correctional data. Data were analyzed using thematic qualitative and descriptive quantitative approaches., Results: Participants had complex histories with opioid use including related negative health outcomes. Experiences with institutional OAT were divergent and provision was not standardized; those with OAT engagement pre-admission did not experience many challenges, whereas those initiating OAT during incarceration experienced barriers such as treatment waitlists and adverse process experiences. Most participants expressed a preference for buprenorphine-naloxone over methadone, but described difficulties accessing it. Participants were keen to transition into community-based treatment, yet envisaged prospective barriers and facilitators concerning successful reintegration and treatment continuity., Conclusions: Major barriers towards the current administration of OAT in federal correctional systems in Canada exist, including extensive waitlists, non-standardized practices, and challenges accessing preferred OAT formulations; this contributes to sub-optimal treatment. Eliminating waitlists, standardizing OAT provision, providing additional OAT options, and more comprehensive release planning may be essential for treatment retention and positive outcomes., (© 2022. The Author(s).)

Abstract: There are few effective treatments for acute whiplash-associated disorders (WADs). Early features of central sensitisation predict poor recovery. The effect of pregabalin on central sensitisation might prevent chronic pain after acute whiplash injury. This double blind, placebo-controlled randomised controlled trial examined feasibility and potential effectiveness of pregabalin compared with placebo for people with acute WAD. Twenty-four participants with acute WAD (<48 hours) and at risk of poor recovery (pain ≥5/10) were recruited from hospital emergency departments in Queensland, Australia, and randomly assigned by concealed allocation to either pregabalin (n = 10) or placebo (n = 14). Pregabalin was commenced at 75 mg bd, titrated to 300 mg bd for 4 weeks, and then weaned over 1 week. Participants were assessed at 5 weeks and 3, 6, and 12 months. Feasibility issues included recruitment difficulties and greater attrition in the placebo group. For the primary clinical outcome of neck pain intensity, attrition at 5 weeks was pregabalin: 10% and placebo: 36% and at 12 months was pregabalin: 10% and placebo: 43%. Pregabalin may be more effective than placebo for the primary clinical outcome of neck pain intensity at 3 months (mean difference: -4.0 [95% confidence interval -6.2 to -1.7]) on an 11-point Numerical Rating Scale. Effects were maintained at 6 months but not 12 months. There were no serious adverse events. Minor adverse events were more common in the pregabalin group. A definitive large randomised controlled trial of pregabalin for acute whiplash injury is warranted. Feasibility issues would need to be addressed with modifications to the protocol., (Copyright © 2021 International Association for the Study of Pain.)

Structural neuroimaging studies of individuals with chronic pain conditions have often observed decreased regional grey matter at a phenotypic level. However, it is not known if this association can be attributed to genetic factors. Here we employed a novel integrative data-driven and hypothesis-testing approach to determine whether there is a genetic basis to grey matter morphology differences in chronic pain. Using publicly available genome-wide association study summary statistics for regional chronic pain conditions (n = 196 963) and structural neuroimaging measures (n = 19 629-34 000), we applied bivariate linkage disequilibrium-score regression and latent causal variable analyses to determine the genetic correlations (rG) and genetic causal proportion (GCP) between these complex traits, respectively. Five a priori brain regions (i.e. prefrontal cortex, cingulate cortex, insula, thalamus and superior temporal gyrus) were selected based on systematic reviews of grey matter morphology studies in chronic pain. Across this evidence-based selection of five brain regions, 10 significant negative genetic correlations (out of 369) were found (false discovery rate < 5%), suggesting a shared genetic basis to both reduced regional grey matter morphology and the presence of chronic pain. Specifically, negative genetic correlations were observed between reduced insula grey matter morphology and chronic pain in the abdomen (mean insula cortical thickness), hips (left insula volume) and neck/shoulders (left and right insula volume). Similarly, a shared genetic basis was found for reduced posterior cingulate cortex volume in chronic pain of the hip (left and right posterior cingulate), neck/shoulder (left posterior cingulate) and chronic pain at any site (left posterior cingulate); and for reduced pars triangularis volume in chronic neck/shoulder (left pars triangularis) and widespread pain (right pars triangularis). Across these negative genetic correlations, a significant genetic causal proportion was only found between mean insula thickness and chronic abdominal pain [rG (standard error, SE) = -0.25 (0.08), P = 1.06 × 10-3; GCP (SE) = -0.69 (0.20), P = 4.96 × 10-4]. This finding suggests that the genes underlying reduced cortical thickness of the insula causally contribute to an increased risk of chronic abdominal pain. Altogether, these results provide independent corroborating evidence for observational reports of decreased grey matter of particular brain regions in chronic pain. Further, we show for the first time that this association is mediated (in part) by genetic factors. These novel findings warrant further investigation into the neurogenetic pathways that underlie the development and prolongation of chronic pain conditions., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Pathophysiologic mechanisms underpinning ongoing pain in whiplash-associated disorder (WAD) are not well understood, however, alterations in brain morphology and function have been observed in this population and in other chronic pain conditions. This study investigated metabolite profiles of brain regions in people with chronic WAD compared with controls., Materials and Methods: Thirty-eight individuals with chronic WAD (mean [SD] age, 39.5 [11.3] years, 23 female individuals) and 16 pain-free controls (38.9 [12.7] years, 11 female individuals) underwent multivoxel brain magnetic resonance spectroscopy. At the anterior cingulate cortex (ACC), primary motor cortex (1MC), and somatosensory cortex (SSC), ratios of metabolite concentrations were calculated for N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myo-inositol (Ins), and glutamate/glutamine (Glx). Chronic WAD group participants completed clinical questionnaires and cold and pressure pain threshold assessment. Data were analyzed with hypothesis testing and Spearman correlations (P≥0.05), with Benjamini-Hochberg corrections (5% false discovery rate)., Results: No group differences were observed for NAA:Cr, NAA:Cho, Cr:Cho, Glx:NAA, Glx:Cr, Glx:Cho, Ins:NAA, Ins:Cr, Ins:Cho or Ins:Glx for left or right ACC, 1MC, or SSC following correction for multiple comparisons. No significant correlations were observed between metabolite ratios and any clinical variable., Discussion: These results suggest that ongoing pain and disability in this population may not be underpinned by metabolite aberrations in the brain regions examined. Further research is required to progress our understanding of cortical contributions to neurophysiologic mechanisms in chronic WAD.

Background and Objective: Mechanisms underpinning symptoms in non-traumatic neck pain (NTNP) and whiplash-associated disorder (WAD) are not comprehensively understood. There is emerging evidence of systemic inflammation in musculoskeletal pain conditions, including neck and back pain. The aim of this systematic review was to determine if raised blood inflammatory markers are associated with neck pain., Databases and Data Treatment: MEDLINE, EMBASE, Cochrane Library, CINAHL and Web of Science databases were searched. Two independent reviewers identified studies for inclusion and extracted data. Meta-analysis was performed by random effects model to calculate standard mean differences (SMDs). Risk of bias of individual studies was assessed using the Newcastle-Ottawa Scale. Overall quality of evidence from meta-analysis was assessed by Grades of Recommendation, Assessment, Development and Evaluation approach., Results: In total, 10 studies were included comprising 706 participants. Three studies provided data for acute WAD, two for chronic WAD, four for chronic NTNP and one for chronic mixed WAD and NTNP. Meta-analysis indicated increased interleukin 1β (SMD: 0.84 [95% CI 0.24, 1.44], p = .01, I 2  = 59%) and tumour necrosis factor α (SMD: 0.59 [0.09, 1.09], p = .02, I 2  = 45%) in chronic neck pain compared to controls, but no increase in monocyte chemoattractant protein-1. Some inflammatory markers were associated with clinical variables (including pain intensity and disability). Quality of evidence was mostly low due to small samples and high heterogeneity., Conclusions: Findings imply that raised blood inflammatory markers are present in chronic neck pain, which may represent an ongoing inflammatory process in this population., Significance: This systematic review advances our understanding of neck pain pathophysiology by demonstrating the presence of systemic inflammation in chronic neck pain, in the form of raised IL-1β and TNFα. Further, numerous inflammatory markers were associated with clinical variables, including pain intensity, disability and hyperalgesia. These findings imply that systemic inflammation may contribute to mechanisms underlying neck pain., (© 2020 European Pain Federation - EFIC®.)

Objective: The composition of cervical-spine meniscoids may have clinical significance in neck-pain conditions, but the accuracy of assessment of meniscoid composition in vivo using magnetic resonance imaging has not been established. The aim of this study was to compare cervical-spine meniscoid composition by magnetic resonance imaging with histologic composition., Methods: Four embalmed cadaveric cervical spines (mean [standard deviation] age, 79.5 [3.7] years; 1 female, 3 male) underwent magnetic resonance imaging, allowing radiologic classification of lateral atlantoaxial- and zygapophyseal-joint (C2-3 to C6-7) meniscoids as either mostly fatty, mixed tissue, or mostly connective tissue. Subsequently, each joint was dissected and disarticulated to allow excision of meniscoids for histologic processing. Each meniscoid was sectioned sagittally, stained with hematoxylin and eosin, examined using light microscopy, and classified as adipose, fibroadipose, or fibrous in composition. Data were analyzed using the kappa statistic with linear weighting., Results: From dissection, 62 meniscoids were identified, excised, and processed; 46 of these 62 were visualized with magnetic resonance imaging. For single-rater identifying structures, agreement between assessment of meniscoid composition by magnetic resonance imaging and by microscopy was fair (κ = 0.24; 95% confidence interval, 0.02-0.46; P = .02)., Conclusion: Findings suggest that the accuracy of this method of magnetic resonance imaging assessment of cervical-spine meniscoid composition may be limited. This should be considered when planning or interpreting research investigating meniscoid composition using magnetic resonance imaging., (Copyright © 2020. Published by Elsevier Inc.)

Background: Mechanisms underpinning ongoing symptoms in chronic whiplash associated-disorder (WAD) are not well understood. People with chronic WAD can exhibit sensory dysfunction consistent with small nerve fibre pathology, including thermal hypoaesthesia and hyperalgesia. This study investigated small fibre structure and function in chronic WAD., Methods: Twenty-four people with chronic WAD (median [IQR] age 49 [15] years, 16 females) and 24 pain-free controls (50 [17] years, 16 females) were recruited. Intraepidermal nerve fibre density (IENFD) and dermal innervation were assessed by skin biopsy. This was performed at (a) the lateral index finger on the primary side of pain and (b) superior to the lateral malleolus on the contralateral side. Quantitative sensory testing was performed over the hand., Results: The WAD group exhibited lower IENFD at the finger (WAD: median [IQR] 4.5 [4.9] fibres/mm; control 7.3 [3.9]; p = .010), but not the ankle (WAD: mean [SD] 7.3 [3.7] fibres/mm; control 9.3 [3.8]; p = .09). Dermal innervation was lower in the WAD group at the finger (WAD: median [IQR] 3.7 [2.8] nerve bundles/mm 2 ; controls: 4.9 [2.1]; p = .017) but not the ankle (WAD: median [IQR] 2.1 [1.9] nerve bundles/mm 2 ; controls: 1.8 [1.8]; p = .70). In the WAD group, hand thermal and light touch detection were impaired, and heat pain thresholds were lowered (p ≤ .037)., Conclusions: Findings suggest small fibre structural and functional deficits in chronic WAD, implicating potential involvement of small fibre pathology., Significance: Our study found decreased intraepidermal nerve fibre density, reduced dermal innervation, thermal hypoaesthesia and hypersensitivity in people with chronic WAD, suggestive of small fibre pathology. This observation of peripheral nervous system pathology in chronic whiplash provides novel insights on mechanisms underpinning symptoms and challenges commonly held beliefs regarding this condition., (© 2020 European Pain Federation - EFIC®.)

Purpose: Injury to the cervical spinal cord has been suggested as a mechanism that may underpin chronic whiplash-associated disorder (WAD). This study aimed to assess metabolite concentrations indicative of neuronal injury or pathology in the cervical cord in people with chronic WAD., Methods: Forty-one people with chronic WAD (mean [SD] age 39.6 [11.0] years, 25 females) and 14 healthy controls (39.2 [12.6] years, 9 females) underwent cervical spinal cord magnetic resonance spectroscopy to measure the metabolites N-acetylaspartate (NAA), creatine (Cr) and choline (Cho). Participants with WAD completed clinical questionnaires on pain intensity (Visual Analogue Scale), disability (Neck Disability Index) and psychological factors (Pain Catastrophising Scale, Post-traumatic Diagnostic Scale), and underwent cervical range of motion assessment and pain threshold testing to cold and pressure stimuli. Data were analysed using hypothesis testing and Spearman correlations (p < 0.05)., Results: There were no differences between the WAD and control groups for NAA/Cr (median [IQR] WAD 1.73 [1.38, 1.97], controls 2.09 [1.28, 2.89], p = 0.37), NAA/Cho (WAD 1.50 [1.18, 2.01], controls 1.57 [1.26, 1.93], p = 0.91) or Cr/Cho (WAD 0.84 [0.64, 1.17], controls 0.76 [0.60, 0.91], p = 0.33). There were no significant correlations between NAA/Cr, NAA/Cho or Cr/Cho and any clinical variable (p ≥ 0.06)., Conclusions: Findings are consistent with major metabolic changes not being present in chronic WAD.

Background: This study describes a low-cost and time-efficient clinical sensory test (CST) battery and evaluates its concurrent validity as a screening tool to detect somatosensory dysfunction as determined using quantitative sensory testing (QST)., Method: Three patient cohorts with carpal tunnel syndrome (CTS, n = 76), non-specific neck and arm pain (NSNAP, n = 40) and lumbar radicular pain/radiculopathy (LR, n = 26) were included. The CST consisted of 13 tests, each corresponding to a QST parameter and evaluating a broad spectrum of sensory functions using thermal (coins, ice cube, hot test tube) and mechanical (cotton wool, von Frey hairs, tuning fork, toothpicks, thumb and eraser pressure) detection and pain thresholds testing both loss and gain of function. Agreement rate, statistical significance and strength of correlation (phi coefficient) between CST and QST parameters were calculated., Results: Several CST parameters (cold, warm and mechanical detection thresholds as well as cold and pressure pain thresholds) were significantly correlated with QST, with a majority demonstrating >60% agreement rates and moderate to relatively strong correlations. However, agreement varied among cohorts. Gain of function parameters showed stronger agreement in the CTS and LR cohorts, whereas loss of function parameters had better agreement in the NSNAP cohort. Other CST parameters (16 mN von Frey tests, vibration detection, heat and mechanical pain thresholds, wind-up ratio) did not significantly correlate with QST., Conclusion: Some of the tests in the CST could help detect somatosensory dysfunction as determined with QST. Parts of the CST could therefore be used as a low-cost screening tool in a clinical setting., Significance: Quantitative sensory testing, albeit considered the gold standard to evaluate somatosensory dysfunction, requires expensive equipment, specialized examiner training and substantial time commitment which challenges its use in a clinical setting. Our study describes a CST as a low-cost and time-efficient alternative. Some of the CST tools (cold, warm, mechanical detection thresholds; pressure pain thresholds) significantly correlated with the respective QST parameters, suggesting that they may be useful in a clinical setting to detect sensory dysfunction., (© 2019 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Neck pain, whether from a traumatic event such as a motor vehicle crash or of a non-traumatic nature, is a leading cause of worldwide disability. This narrative review evaluated the evidence from systematic reviews, recent randomised controlled trials, clinical practice guidelines, and other relevant studies for the effects of rehabilitation approaches for chronic neck pain. Rehabilitation was defined as the aim to restore a person to health or normal life through training and therapy and as such, passive interventions applied in isolation were not considered. The results of this review found that the strongest treatment effects to date are those associated with exercise. Strengthening exercises of the neck and upper quadrant have a moderate effect on neck pain in the short-term. The evidence was of moderate quality at best, indicating that future research will likely change these conclusions. Lower quality evidence and smaller effects were found for other exercise approaches. Other treatments, including education/advice and psychological treatment, showed only very small to small effects, based on low to moderate quality evidence. The review also provided suggestions for promising future directions for clinical practice and research.

Background: There is uncertainty regarding the clinical significance of findings on MRI in patients with whiplash associated disorder (WAD) or nonspecific neck pain (NSNP)., Purpose: To compare the presence of cervical spine MRI findings in people with WAD or NSNP with pain-free controls., Study Type: Systematic review and meta-analysis., Population: Adults with WAD (n = 994), NSNP (n = 715), or pain-free controls (n = 2323)., Field Strength: 0.5T, 1.5T, and 3.0T., Assessment: Medline, EMBASE, CINAHL, Web of Science, SCOPUS, and Cochrane CENTRAL databases were searched. Two independent reviewers identified studies for inclusion and extracted data. Risk of bias was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Overall quality of the evidence from meta-analysis was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation approach., Statistical Tests: Meta-analysis was performed using a random-effects model to calculate odds ratios or standard mean differences (SMDs) for binary and continuous data., Results: In total, 31 studies were included (eight comparing acute WAD to controls, 14 comparing chronic WAD to controls, 12 comparing chronic NSNP to controls) comprising 4032 participants. Rectus capitis posterior major cross-sectional area was smaller in people with chronic NSNP than controls (two studies: SMD -1.18 [95% confidence interval [CI] -1.65, -0.71]). The remaining meta-analysis comparisons showed no group differences in MRI findings. The quality of evidence was mostly low due to small sample sizes and high heterogeneity., Data Conclusion: Given the typically low-quality evidence, definitive conclusions cannot be drawn on the presence of MRI findings in individuals with WAD or NSNP compared with pain-free controls., Level of Evidence: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: Lateral atlantoaxial (LAA) joint meniscoid composition may have clinical significance in patients following neck trauma. However, the existing method of radiologically assessing meniscoid composition has an inherent element of subjectivity, which could contribute to measurement variability. The present study sought to investigate the accuracy of two-point Dixon fat/water separation MRI as a quantitative assessment of LAA joint meniscoid composition., Methods: Sixteen LAA joint meniscoids were excised from four cadavers (mean [SD] age 79.5 [3.7] years; one female) following cervical spine MRI (two-point Dixon, T1-weighted VIBE and T2-weighted SPACE sequences). Composition of LAA joint meniscoids was undertaken by (1) histological examination by light microscopy, (2) calculation of fat fraction by Dixon MRI (both in-phase/opposed-phase and fat/water methods), and (3) the existing method of considering VIBE and SPACE signal intensities. Analysis was performed using the kappa statistic with linear weighting., Results: Microscopy revealed three, five, and eight meniscoids to be composed of adipose, fibroadipose, and fibrous tissues, respectively. Dixon sequence MRI classified 11 of these meniscoids correctly, with 'substantial' level of agreement (In-phase/Opp-phase kappa statistic = 0.78 [95% CI 0.38, 1.17]; fat/water kappa statistic = 0.72 [95% CI 0.32, 1.11]). Level of agreement between microscopy and the VIBE and SPACE method was 'slight' (kappa statistic = 0.02 [95% CI - 0.34, 0.38])., Conclusions: Findings suggest that Dixon fat/water separation MRI may have superior utility in the assessment of LAA joint meniscoid composition than the existing method of considering VIBE and SPACE signal intensities. These slides can be retrieved under Electronic Supplementary Material.

Background and aims Impairment of endogenous analgesia has been associated with the development, maintenance and persistence of pain. Endogenous analgesia can be evaluated using exercise-induced hypoalgesia (EIH) and offset analgesia (OffA) paradigms, which measure temporal filtering of sensory information. It is not clear if these paradigms are underpinned by common mechanisms, as EIH and OffA have not previously been directly compared. A further understanding of the processes responsible for these clinically relevant phenomena may have future diagnostic and therapeutic utility in management of individuals with persistent pain conditions. The primary aim of this study was to investigate if there is a correlation between the magnitudes of EIH and OffA. The secondary aim of the study was to examine whether exercise influences OffA. Methods Thirty-six healthy, pain-free participants were recruited. EIH was evaluated using pressure pain thresholds (PPT) and pain ratings to suprathreshold pressure stimuli over tibialis anterior and the cervical spine. OffA evaluation utilised a three-step protocol, whereby individualised heat pain thermal stimuli [Numerical Rating Scale (NRS)=50/100] were applied (T1), before increasing 1 °C (T2), followed by 1 °C reduction (T3). The magnitude of OffA was calculated as the percentage reduction in the NRS from T2 to T3. PPT/suprathreshold pain ratings and OffA measures were recorded, before and after 5 min of isometric quadriceps exercise performed at 20-25% maximum voluntary contraction (MVC); and following a 15 min rest period. Data were analysed using repeated measures (RM) ANCOVA and correlational analyses. Results There was no correlation between EIH measures (PPTs or pain ratings to suprathreshold pressure stimuli over tibialis anterior or the cervical spine) and OffA (p>0.11 for all). OffA was induced and not modulated by exercise (p=0.28). Conclusions Five minutes of 20-25% MVC lower limb isometric exercise provided non-pharmacological pain modulation in young, active adults. Magnitude of EIH was not correlated with that of OffA, and exercise did not influence magnitude of OffA. Implications These results suggest that in young, pain-free individuals, separate testing of these two paradigms is required to comprehensively evaluate efficacy of endogenous analgesia. If these results are replicated in patient populations, alternative or complementary methods to exercise interventions may be required to modulate impaired OffA.

Context:   Scapular taping can offer clinical benefit to some patients with shoulder pain; however, the underlying mechanisms are unclear. Understanding these mechanisms may guide the development of treatment strategies for managing neuromusculoskeletal shoulder conditions., Objective:   To examine the mechanisms underpinning the benefits of scapular taping., Design:   Descriptive laboratory study., Setting:   University laboratory., Patients or Other Participants:   A total of 15 individuals (8 men, 7 women; age = 31.0 ± 12.4 years, height = 170.9 ± 7.6 cm, mass = 73.8 ± 14.4 kg) with no history of shoulder pain., Intervention(s):   Scapular taping., Main Outcome Measure(s):   Surface electromyography (EMG) was used to assess the (1) magnitude and onset of contraction of the upper trapezius (UT), lower trapezius (LT), and serratus anterior relative to the contraction of the middle deltoid during active shoulder flexion and abduction and (2) corticomotor excitability (amplitude of motor-evoked potentials from transcranial magnetic stimulation) of these muscles at rest and during isometric abduction. Active shoulder-flexion and shoulder-abduction range of motion were also evaluated. All outcomes were measured before taping, immediately after taping, 24 hours after taping with the original tape on, and 24 hours after taping with the tape removed., Results:   Onset of contractions occurred earlier immediately after taping than before taping during abduction for the UT (34.18 ± 118.91 milliseconds and 93.95 ± 106.33 milliseconds, respectively, after middle deltoid contraction; P = .02) and during flexion for the LT (110.02 ± 109.83 milliseconds and 5.94 ± 92.35 milliseconds, respectively, before middle deltoid contraction; P = .06). These changes were not maintained 24 hours after taping. Mean motor-evoked potential onset of the middle deltoid was earlier at 24 hours after taping (tape on = 7.20 ± 4.33 milliseconds) than before taping (8.71 ± 5.24 milliseconds, P = .008). We observed no differences in peak root mean square EMG activity or corticomotor excitability of the scapular muscles among any time frames., Conclusions:   Scapular taping was associated with the earlier onset of UT and LT contractions during shoulder abduction and flexion, respectively. Altered corticomotor excitability did not underpin earlier EMG onsets of activity after taping in this sample. Our findings suggested that the optimal time to engage in rehabilitative exercises to facilitate onset of trapezius contractions during shoulder movements may be immediately after tape application.

Background: Lateral atlantoaxial (LAA) joints are established sources of nociceptive input in chronic whiplash associated disorder (WAD). These joints contain intra-articular meniscoids that may be damaged in whiplash trauma. LAA joint meniscoid morphology has not been investigated comprehensively in a chronic WAD population, and it is unclear whether morphological differences exist compared to a pain-free population., Objectives: This study examined LAA joint meniscoid volume in individuals with chronic WAD who report pain in a distribution consistent with LAA joint pain., Design: Case-control study., Method: Fourteen individuals with chronic WAD with pain in an LAA joint distribution (mean [SD] age 38.1 [10.8] years; six female) and 14 age- and sex-matched pain-free controls (38.0 [10.5] years) underwent cervical spine magnetic resonance imaging. LAA joint images were inspected for meniscoids; meniscoid volume was calculated in mm 3 and as a percentage of articular cavity volume. Symptom duration, location and intensity were recorded. Data were analysed using paired t-tests, Wilcoxon signed-rank testing, Spearman's rank testing, linear and logistic regression (α < 0.05)., Results: Ventral and dorsal meniscoids (n = 112) were found in each LAA joint. Greater dorsal meniscoid volume as a percentage of articular cavity volume was associated with higher pain intensity (odds ratio 1.48, p = 0.03; likelihood ratio test chi-square 2  = 6.64, p = 0.04), however no significant differences existed between meniscoid volumes of WAD and control participants., Conclusions: Findings indicate a potential link between dorsal LAA joint meniscoid volume and pain, suggesting larger meniscoid size may have pathoanatomical significance in WAD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Whiplash-associated disorders (WAD) are an enormous and costly burden to Australian society. Up to 50% of people who experience a whiplash injury will never fully recover. Whiplash is resistant to treatment and no early management approach has yet been shown to prevent chronic pain. The early presence of central sensitization is associated with poor recovery. Pregabalin's effects on central sensitization indicate the potential to prevent or modulate these processes after whiplash injury and to improve health outcomes, but this has not been investigated. This paper describes the protocol for a feasibility study for a randomised controlled trial of pregabalin plus evidence-based advice compared to placebo plus evidence-based advice for individuals with acute whiplash injury who are at risk of poor recovery., Methods: This double blind, placebo-controlled randomised feasibility study will examine the feasibility and potential effectiveness of pregabalin and evidence-based advice (intervention) compared to placebo and evidence-based advice (control) for individuals with acute whiplash injury at risk of poor recovery. Thirty participants (15 per group) aged 18-65 years with Grade II WAD, within 48 hours of injury and currently experiencing at least moderate pain (NRS: ≥ 5/10) will be recruited from Emergency Departments of public hospitals in Queensland, Australia. Pregabalin will be commenced at 75 mg bd and titrated up to 300 mg bd as tolerated for 4 weeks followed by 1 week of weaning., Results: The feasibility of trial procedures will be tested, as well as the potential effect of the intervention on the outcomes. The primary outcome of neck pain intensity at 3 months from randomisation will be compared between the treatment groups using standard analysis of variance techniques., Discussion: Feasibility and potential effectiveness data will inform an appropriately powered full trial, which if successful, will provide an effective and cost-effective intervention for a costly and treatment resistant condition. It will also have implications for the early management of other traumatic conditions beyond whiplash., Trial Registration: Clinical Trials Primary Registry: Australian and New Zealand Clinical Trials Registry., Clinical Trial Registration Number: ACTRN12617000059369 . Date of Registration: 11/01/2017. Primary Trial Sponsor: The University of Queensland, Brisbane QLD 4072 Australia.

Objectives: (1) To identify reported tests used to assess sensorimotor control in individuals with idiopathic neck pain and (2) to investigate whether these tests can quantify differences between individuals with idiopathic neck pain and healthy individuals., Data Sources: Allied and Complementary Medicine Database, CINAHL, Cochrane Central Register of Controlled Trials, Embase, MEDLINE, Physiotherapy Evidence Database, Scopus, and SPORTDiscus., Study Selection: Studies reporting sensorimotor outcomes in individuals with idiopathic neck pain or healthy individuals were identified. There were 1,677 records screened independently by 2 researchers for eligibility: 43 studies were included in the review, with 30 of these studies included in the meta-analysis., Data Extraction: Methodologic quality was determined using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Data were extracted using a standardized extraction table., Data Synthesis: Sensorimotor control was most commonly assessed by joint position error and postural sway. Pooled means for joint position error after cervical rotation in individuals with neck pain (range, 2.2°-9.8°) differed significantly (P=.04) compared with healthy individuals (range, 1.66°-5.1°). Postural sway with eyes open ranged from 4.85 to 10.5cm 2 (neck pain) and 3.5 to 6.6cm 2 (healthy) (P=.16), and postural sway with eyes closed ranged from 2.51 to 16.6cm 2 (neck pain) and 2.74 to 10.9cm 2 (healthy) (P=.30). Individual studies, but not meta-analysis, demonstrated differences between neck pain and healthy groups for postural sway. Other test conditions and other tests were not sufficiently investigated to enable pooling of data., Conclusions: The findings from this review suggest sensorimotor control testing may be clinically useful in individuals with idiopathic neck pain. However, results should be interpreted with caution because clinical differences were small; therefore, further cross-sectional research with larger samples is needed to determine the magnitude of the relation between sensorimotor control and pain and to assess any potential clinical significance., (Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Cervical spine meniscoids are intra-articular folds of synovial membrane that have been theorised to have potential clinical significance in neck pain. Recent anatomical and clinical research has re-visited the pathoanatomical capacity of these structures. The purpose of this review is to discuss cervical spine meniscoid morphology in light of recently published work, to provide an update on the plausible relevance of these structures to clinical practice., Methods: Narrative review critically discussing basic science and clinical research regarding cervical spine meniscoids, with focus upon implications for clinical practice., Results: Basic science research indicates that cervical spine meniscoids can be innervated and appear to vary in morphology in the presence of articular degeneration. In a clinical population, associations have been observed between cervical spine meniscoid morphology and presence of cervical spine symptoms., Conclusions: Recent studies regarding cervical spine meniscoid morphology provide further evidence of pathoanatomical capacity of these structures. Further research is required, however, in clinical populations to empirically investigate specific theorised mechanisms of cervical spine meniscoid involvement in neck pain.

Studies imply that intestinal barrier dysfunction is a key contributor to morbid events associated with sepsis. Recently, co-inhibitory molecule, programmed death-ligand1 (PD-L1) has been shown to be involved in the regulation of intestinal immune tolerance and/or inflammation. Our previous studies showed that PD-L1 gene deficiency reduced sepsis-induced intestinal injury morphologically. However, it isn't known how PD-L1 expression impacts intestinal barrier dysfunction during sepsis. Here we tested the hypothesis that PD-L1 expressed on intestinal epithelial cells (IECs) has a role in sepsis-induced intestinal barrier dysfunction. To address this, C57BL/6 or PD-L1 gene knockout mice were subjected to experimental sepsis and PD-L1 expression, intestinal permeability, tissue cytokine levels were assessed. Subsequently, septic or non-septic patient colonic samples (assigned by pathology report) were immunohistochemically stained for PD-L1 I a blinded fashion. Finally, human Caco2 cells were used for in vitro studies. The results demonstrated that PD-L1 was constitutively expressed and sepsis significantly up-regulates PD-L1 in IECs from C57BL/6 mice. Concurrently, we observed an increased PD-L1 expression in colon tissue samples from septic patients. PD-L1 gene deficiency reduced ileal permeability, tissue levels of IL-6, TNF-α and MCP-1, and prevented ileal tight junction protein loss compared to WT after sepsis. Comparatively, while Caco2 cell monolayers responded to inflammatory cytokine stimulation also with elevated PD-L1 expression, increased monolayer permeability and altering/decreasing monolayer tight junction protein morphology/expression; these changes were reversed by PD-L1 blocking antibody. Together these data indicate that ligation of ICE PD-L1 plays a novel role in mediating the pathophysiology of sepsis-induced intestinal barrier dysfunction.

Study Design Case-control study. Background Cervical spine meniscoids are thought to contribute to neck pain and hypomobility in individuals with chronic whiplash-associated disorder (WAD); however, their morphology has not been studied in a clinical population. Objectives To investigate cervical spine meniscoid morphology in individuals with chronic WAD. Methods Twenty volunteers with chronic WAD (mean ± SD age, 39.3 ± 11.0 years; 10 female) and 20 age- and sex-matched controls (age, 39.1 ± 10.6 years) underwent cervical spine magnetic resonance imaging. Lateral atlantoaxial and zygapophyseal joints (C2-3 to C6-7) were inspected for meniscoids. Length of meniscoid protrusion was measured and composition (adipose/fibrous/fibroadipose) assessed. Data were analyzed using Wilcoxon signed-rank tests and linear and logistic regression (P<.05). Results Meniscoids were identified in the chronic WAD (n = 317) and control (n = 296) groups. At the lateral atlantoaxial joints, median meniscoid length was greater in the control group (ventral, 6.07 mm; dorsal, 7.24 mm) than the WAD group (ventral, 5.01 mm; P = .06 and dorsal, 6.48 mm; P<.01). At the dorsal aspect of zygapophyseal joints, meniscoids were more frequently fibrous in the chronic WAD group (odds ratio = 2.38, P<.01; likelihood ratio test: χ 2 2 , 9.02; P = .01). Conclusion In individuals with chronic WAD, lateral atlantoaxial meniscoids were shorter and dorsal cervical zygapophyseal meniscoids were more fibrous, suggesting alterations in meniscoid composition. This may have pathoanatomical implications in chronic WAD. J Orthop Sports Phys Ther 2016;46(10):902-910. Epub 3 Sep 2016. doi:10.2519/jospt.2016.6702.

Background Context: Innervation of anatomical structures is fundamental to their capacity to generate nociceptive impulses. Cervical spine meniscoids are hypothesized to be contributors to neck pain; however, their innervation is not comprehensively understood., Purpose: This study aimed to examine the presence and morphology of nerve fibers within cervical spine meniscoids and adjacent joint capsules., Study Design: This is a cross-sectional study., Patient Sample: The sample consists of cervical hemispines of 12 embalmed cadavers (mean [standard deviation] age 82.9 [6.5] years, six female, six left). Either the right or the left half of the cervical spine (hemispine) of each cadaver was included in the sample. So six left sides and six right sides of the cadaver cervical spines made up the 12 hemispines that formed the sample., Methods: Cervical spine meniscoids and adjacent joint capsules were excised from lateral atlantoaxial and cervical zygapophyseal (C2-C3 to C6-C7) joints (n=67), then paraffin embedded. Meniscoids were sectioned sagittally (5 µm), slide mounted, and immunohistochemistry was performed using primary antibodies to neurofilament heavy (NF-H) and pan-neurofilament (Pan-NF) to identify nerve tissue. The study was supported by institutional graduate student funding. The authors have no conflicts of interest to declare., Results: Seventy-seven meniscoids (23 lateral atlantoaxial, 54 cervical zygapophyseal) were extracted and processed (154 sections in total). Sixty-four individual nerve fiber bundles were identified (26 NF-H positive, 38 Pan-NF positive) from 14 meniscoids. Nerves immunoreactive to both NF-H and Pan-NF were identified in 13 of 77 meniscoids (10 of 14 lateral atlantoaxial joint) from 11 joints (eight cadavers). Nerves were always located in joint capsules except three exclusively Pan-NF immunoreactive nerve fiber bundles from two adipose meniscoids., Conclusions: The low nerve prevalence in elderly cervical spine meniscoids, with nerves only found in two adipose type meniscoids, suggests these structures may play a minimal role in cervical nociception generation in this demographic. The joint capsules, which were more frequently innervated, appear to be more likely generators of nociception in the elderly. Joint capsule nerves were mostly NF-H positive, indicating potential Aδ-fiber presence., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The lateral atlantoaxial joints contain folds of synovium termed meniscoids that may potentially contribute to cervical spine pain; however, the anatomy of these structures has not been comprehensively investigated. The purpose of this study was to explore the morphology and morphometry of lateral atlantoaxial joint meniscoids. Twelve cadaveric hemi-spines (6 female; 6 left; mean 81.5 years, SD 7.3) were obtained for dissection and disarticulation of the lateral atlantoaxial joints. Meniscoids were identified and measurements made of surface area, length, and surrounding articular cartilage degeneration. Tissue was sectioned sagittally, stained with hematoxylin and eosin, and examined by light microscopy. Data were analyzed descriptively and using nonparametric techniques. Ventral and dorsal meniscoids (24 in total) were found in each joint, and could be classified histologically into adipose (32%), fibrous (41%), and fibroadipose (27%) meniscoids. No significant associations were found between meniscoid size and age, histology, cartilage degeneration, or joint position. Meniscoid length in males was significantly greater than in females (P = 0.04). Fibrous meniscoids were noted to be associated with articular cartilage degeneration, and adipose and fibroadipose meniscoids with intact cartilage (P = 0.05). Fibrous meniscoids tended to be located dorsally (78%), whereas adipose meniscoids were mostly located ventrally (86%). Distinct patterns in lateral atlantoaxial joint meniscoid morphology were observed, including the association of fibrous meniscoid composition with dorsal joint position and articular cartilage degeneration. The clinical significance of these patterns remains uncertain, and further research is needed to examine these structures across the lifespan and in cervical pathology.

Patients, providers and policy-makers rely heavily on comparative effectiveness research (CER) when making complex, real-world medical decisions. In particular, Medicaid providers and policy-makers face unique challenges in decision-making because their program cares for traditionally underserved populations, especially children, pregnant women and people with mental illness. Because these patient populations have generally been underrepresented in research discussions, CER questions for these groups may be understudied. To address this problem, the Agency for Healthcare Research and Quality commissioned our team to work with Medicaid Medical Directors and other stakeholders to identify relevant CER questions. Through an iterative process of topic identification and refinement, we developed relevant, feasible and actionable questions based on issues affecting Medicaid programs nationwide. We describe challenges and limitations and provide recommendations for future stakeholder engagement.

Purpose: Meniscoids are folds of synovial membrane that project into the articular cavities of zygapophyseal joints throughout the cervical spine. These structures have been implicated in musculoskeletal neck pain; however, their anatomy has not been extensively investigated. The purpose of this study was to explore the morphometry and composition of the cervical zygapohyseal joint meniscoids., Methods: Twelve adult cadaveric hemi-spines were dissected and their C2-3 to C6-7 zygapophyseal joints disarticulated (six female; six left; mean 81.5 years, SD 7.3 years). Meniscoids were identified and their surface area, protrusion length and articular cartilage degeneration measured. Specimens were then sectioned sagittally, stained with haematoxylin and eosin, and examined with a light microscope. Data were analysed descriptively and using non-parametric hypothesis testing (significance p < 0.05)., Results: Meniscoids were identified in 86% of zygapophyseal joints examined; 50% contained both ventral and dorsal meniscoids, 7% contained a ventral meniscoid only and 29% contained a dorsal meniscoid only. Meniscoids were classified as adipose (4%), fibrous (74%), or fibroadipose (22%) based upon histological composition. There were no significant associations between meniscoid size (surface area or protrusion length) and gender, position in joint, spinal level, or articular degeneration. Increased articular degeneration was associated with fibrous meniscoid classification., Conclusions: The morphological patterns observed, such as the association of fibrous meniscoids with cartilage degeneration, may provide insight into the significance of the zygapophyseal joint meniscoids in neck pathology. Further investigation is needed to explore the morphological qualities of these structures in a pathological population.

Purpose: To investigate how musculoskeletal outpatient physiotherapists in public hospitals interact with and perceive clinical anatomy resources in the workplace., Method: This cross-sectional study used a postal survey sent to musculoskeletal outpatient physiotherapists in 64 Australian public hospitals. Survey questions examined demographics, qualifications, experience, types of resources used, whether resources meet requirements, and what improvements could be made to current resources., Results: A total of 193 physiotherapists responded (75% response rate; 60% female), of whom 49% were age 35 years or younger; 67% had only an undergraduate qualification, and 37% had practised for 5 years or less. More experienced physiotherapists used resources significantly less frequently ([odds ratio]=1.35; 95% CI, 1.17-1.57), and we found no significant associations between preference for online versus printed resources and age, sex, qualifications, or experience. Trends included less experienced physiotherapists identifying the absence of online access as a barrier to resource use and provision of improved online facilities as necessary to improve access to clinical anatomy resources., Conclusion: RESULTS indicate distinct trends in physiotherapists' use of clinical anatomy resources, including a desire for improved online resource access on the part of less experienced physiotherapists. The findings are relevant to hospital outpatient clinics, particularly those that employ less experienced physiotherapists.

Demineralization can facilitate the dissection of soft tissue structures in inaccessible locations by softening surrounding bone so that it can be easily removed without risking damage to the structure of interest. However, it is unclear whether demineralization alters the morphometry of soft tissues if used for this purpose. We have therefore examined the effect of extended-immersion formic acid demineralization on the size and shape of cervical zygapophyseal joint meniscoids to evaluate its usefulness as a means of facilitating dissection and examination of soft tissue structures from bony regions. Four cadaveric cervical spines were dissected, and three randomly selected zygapophyseal joints from each spine (12 in total) were removed, disarticulated and immersed in 5% formic acid for 32 days. Each joint was examined using a surgical microscope and photographed, and meniscoid length and surface area measured at days 0, 4, 18, and 32. Measurements were made on magnified digital photographs, and each measurement was repeated three times to determine intra-rater reliability. Data were analyzed using repeated-measures analysis of variance. Significance was set at p < 0.05. There were no significant differences between any of the measures over time for all of the variables assessed (F = 0.302-1.576, p = 0.226-0.759, partial η (2) = 0.029-0.136). For all measurements, intra-rater reliability was high (intra-class correlation > 0.9). These results support the use of formic acid demineralization to facilitate the study of cervical spine meniscoids by dissection, as even after a period of extended immersion in the solution, the morphometry of the structures was not significantly altered. Findings may have implications for dissection studies of other meniscoid-like soft tissue structures that use formic acid demineralization.

The Myc family of transcription factors regulates a variety of biological processes, including the cell cycle, growth, proliferation, metabolism, and apoptosis. In Caenorhabditis elegans, the "Myc interaction network" consists of two opposing heterodimeric complexes with antagonistic functions in transcriptional control: the Myc-Mondo:Mlx transcriptional activation complex and the Mad:Max transcriptional repression complex. In C. elegans, Mondo, Mlx, Mad, and Max are encoded by mml-1, mxl-2, mdl-1, and mxl-1, respectively. Here we show a similar antagonistic role for the C. elegans Myc-Mondo and Mad complexes in longevity control. Loss of mml-1 or mxl-2 shortens C. elegans lifespan. In contrast, loss of mdl-1 or mxl-1 increases longevity, dependent upon MML-1:MXL-2. The MML-1:MXL-2 and MDL-1:MXL-1 complexes function in both the insulin signaling and dietary restriction pathways. Furthermore, decreased insulin-like/IGF-1 signaling (ILS) or conditions of dietary restriction increase the accumulation of MML-1, consistent with the notion that the Myc family members function as sensors of metabolic status. Additionally, we find that Myc family members are regulated by distinct mechanisms, which would allow for integrated control of gene expression from diverse signals of metabolic status. We compared putative target genes based on ChIP-sequencing data in the modENCODE project and found significant overlap in genomic DNA binding between the major effectors of ILS (DAF-16/FoxO), DR (PHA-4/FoxA), and Myc family (MDL-1/Mad/Mxd) at common target genes, which suggests that diverse signals of metabolic status converge on overlapping transcriptional programs that influence aging. Consistent with this, there is over-enrichment at these common targets for genes that function in lifespan, stress response, and carbohydrate metabolism. Additionally, we find that Myc family members are also involved in stress response and the maintenance of protein homeostasis. Collectively, these findings indicate that Myc family members integrate diverse signals of metabolic status, to coordinate overlapping metabolic and cytoprotective transcriptional programs that determine the progression of aging.

Objective: The atlantodental interval (ADI) is used in assessing atlantoaxial stability. This measurement may potentially be affected by several features encountered during patient examination. This study examined the influence of 3 features: age, sex, and posture, on the measurement of ADI in a normal population., Methods: The ADI was measured sequentially on 269 lateral cervical radiographs of adults with no demonstrated bony injury. Images were stratified by age and sex with equal representation in each age group. A further 25 asymptomatic adults were assessed for posture using craniovertebral angle measured from digital lateral photographs. The ADI was then measured from a lateral radiograph. The data were examined for correlation between age, craniovertebral angle, and ADI using Spearman rank correlation. The ADI of age groups was compared by Kruskal-Wallis test. The relationship between ADI and sex was examined using Wilcoxon rank sum test. Interaction between age and sex was explored using an interaction term in regression analysis., Results: The ADI decreased with age, median measurements reducing from 2.07 to 0.85 mm across age groups (P < .01). No significant relationship was demonstrated between ADI and sex. No significant interaction was demonstrated between age and sex. Measurements of craniovertebral angle did not correlate with ADI (ρ = 0.03, P = .90)., Conclusion: The magnitude of ADI decreases with advancing age. Age should be considered a modifying factor when interpreting measurement of ADI, particularly in consideration of potential minor instabilities. Patient sex does not appear to influence ADI, either independently or in interaction with age. Craniocervical posture variation does not influence ADI in an asymptomatic adult population., (Copyright © 2013 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.)

Background: The prevalence of illicit drug use among correctional populations is high, and associated with high levels of drug related morbidity risks and harms. The purpose of this study was to examine temporal and regional patterns of illicit drug use among a sample of Canadian federal correctional inmates participating in correctional methadone maintenance treatment (MMT)., Methods: Socio-demographic and drug use data collected from 1272 male federal offenders admitted to Correctional Service Canada's (CSC) MMT program between 2003 and 2008 were examined. Univariate analyses were conducted on inmates' key demographic and correctional characteristics, pre-MMT opioid use and other problematic drug use, and opioid and injecting use while incarcerated. Bivariate associations on drug use measures across regions and over time were computed., Results: Prevalence of heroin use decreased, and prevalence of prescription opioid (PO) use increased over the study period. Significant regional differences existed for PO use, specifically for morphine/hydromorphone and oxycodone use. The majority used opioids and injected while incarcerated, with overall downward trends over time and regional variations. Approximately half the sample indicated a history of lifetime non-opioid problematic drug use, most commonly cocaine (72%) for which substantial regional differences were found., Conclusions: Pre-MMT opioid and other problematic non-opioid drug use in the sample was high. Temporal and regional patterns of drug use observed may reflect developments in the general population, e.g. increasing PO misuse. The observed drug use patterns underscore the need for targeted drug specific prevention/treatment measures in correctional environments beyond existing interventions., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The current study examined acute and long-term effects of anabolic-androgenic steroid (AAS) exposure during puberty on copulation, vocalizations, scent marking, and intermale aggression, both with and without tail pinch, in intact male rats. Animals received 5 mg/kg of testosterone, nandrolone, stanozolol, or vehicle, beginning at puberty. After 5 weeks, behavior tests were performed while continuing AAS injections. AAS treatment was then discontinued. Behaviors were tested during 3-5 weeks, 9-11 weeks, and 15-17 weeks of withdrawal. During AAS administration, stanozolol males showed significant reductions in all behaviors compared with controls, except aggression with tail pinch. Nandrolone treatment significantly reduced vocalizations and scent marking, and testosterone had no significant effect on behavior. During withdrawal, behaviors in stanozolol males recovered to control levels at variable rates: aggression at 4 weeks; mounts, vocalizations, and scent marking at 9 weeks; and ejaculations at 15 weeks of withdrawal. Stanozolol males showed significantly higher levels of tail pinch-induced aggression during every withdrawal test. Nandrolone-treated males scent-marked at control levels by 9 weeks withdrawal but displayed significantly fewer vocalizations and significantly more tail pinch-induced aggression than controls for the entire study. Testosterone-treated males scent-marked significantly below controls at 3 weeks withdrawal and showed significantly more tail pinch-induced aggression at 5 weeks withdrawal. All three AAS significantly increased tail pinch-induced aggression compared with corresponding nontail pinch tests, even at study endpoint. These results suggest that alterations in androgen-dependent behaviors by pubertal AAS exposure can persist long after drug exposure, and some effects may even be permanent.

Adolescence in human males is a hormonally sensitive period when many adult behaviors develop, including sexual and aggressive behaviors. Using a rat model, the authors examined the effects of three anabolic-androgenic steroids (AAS) during puberty: testosterone, nandrolone, and stanozolol. Copulation, vocalizations, scent-marking, and aggression were tested following AAS exposure. Relative to gonadally intact controls, rats injected with testosterone showed a significant increase in scent-marking and aggression in the opponent's home cage. Nandrolone had no effect. Stanozolol significantly inhibited all behaviors. Results suggest that depending on the chemical structure of the steroid, AAS exposure during puberty affects several androgen-dependent behaviors. Because adolescence in humans is a period of hormonal change, abuse of AAS, particularly stanozolol, during this time may disrupt the establishment of normal adult behavior patterns., ((c) 2003 APA, all rights reserved)