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Background & Objective Cervical spine radiculopathy (CSR) is a disabling condition which has significant negative impacts on a person’s mental health, physical functioning and social participation. Research has reported variable CSR incidence and prevalence among different populations. To date no systematic review has been completed investigating the prevalence or incidence of CSR, therefore our objective was to determine the incidence and/or prevalence of CSR in adults. Design and Method A systematic review was conducted including searches of PubMed (MEDLINE), EMBASE and CINAHL from inception to February 25th 2020. Studies including data on incidence and/or prevalence of CSR were included. Methodological quality was assessed using a modified Hayden, Cote and Bombardier (2006) appraisal checklist. Data was analysed narratively. Results Nine low to high-quality studies were included in the final review. Incidence ranged between 0.832 to 1.79 per 1000 person-years from two high quality and one low quality study. Prevalence values ranged from 1.21 to 5.8 per 1000 from four medium to high quality studies. Prevalence values of 1.14% (95% CI 0.45-1.82) and 1.31% (95% CI 0.66-1.96) for males and females respectively were reported from one medium quality study. One medium quality study reported an unadjusted prevalence value of 6.3% for males and females. Conclusions This is the first systematic review investigating the epidemiology of CSR in an adult population. This review reports a variable incidence rate and prevalence of CSR among specific populations, however, this was based on nine studies. There is a priority to investigate CSR epidemiology across other populations globally and standardising CSR diagnostic criteria. This is the peer reviewed version of the following article: Mansfield et al. (2020) Cervical Spine Radiculopathy Epidemiology. Systematic Review, Musculoskeletal Care which will be published in final form at https://onlinelibrary.wiley.com/journal/15570681. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

Systematic review protocol assessing associations between psychosocial factors and/or mental health symptoms and health outcomes in adults with cervical spine pain with or without radiculopathy., Introduction: Cervical spine pain with or without radiculopathy (CSp ± R) has significant negative impacts to a person's quality of life. Psychosocial factors and/or mental health symptoms are associated with spinal pain with or without radiculopathy and negatively impact health outcomes. This area of research is not yet established for CSp ± R. Our objective is to conduct a systematic review assessing the association between psychosocial factors and/or mental health symptoms and health outcomes in adults with CSp ± R. Methods: A systematic electronic search of 3 online databases will retrieve studies in which adults (older than 18 years) with CSp ± R, assessing how psychosocial factors or mental health symptoms impact outcomes related to disability, pain, and/or healthcare utilisation. Data extracted will include study design, CSp ± R definition, psychosocial and/or mental health symptoms, and health outcomes. Reporting study quality through the Newcastle–Ottawa Quality Scale Assessment and certainty through Grading of Recommendations, Assessment, Development and Evaluations will be completed. Studies will be assessed from a clinical perspective, methodology design, and statistical testing to determine whether studies can be pooled for meta-analysis. If there is significant clinical heterogeneity, narrative description will be undertaken. Perspective: This will be a comprehensive synthesis review to enhance understanding of the association of psychosocial factors and/or mental health symptoms and CSp ± R on health outcomes. The findings will support the formulation of prognosis, collaborative management decisions, and guide healthcare resources to improve outcomes for this patient group. The review will identify gaps in research, thereby informing future experimental and observational study design.

Background :The best approach to rehabilitate the control of everyday whole-body movement (e.g. rise-to-walk) after pathology remains unclear in part because the associated controlled performance variables are not known. Rise-to-walk can be performed fluidly (sit-to-walk) or non-fluidly (sit-to-stand, proceeded by gait-initiation). Biomechanical variables that remain consistent in health regardless of how rise-to walk is performed represent controlled performance variable candidates which could monitor rehabilitative change. Research Question :To determine if any biomechanical parameters remain consistent across rising-to-walk (RTW) subtasks (sit-to-stand, gait-initiation, and sit-to-walk) in healthy adults for purposes of movement control assessment in clinical practice. Methods :Data sources included Medline, Cinahl, and Scopus databases, and the grey literature. Study selection was based on eligibility criteria and must have reported spatiotemporal, kinematic and/or kinetic biomechanical parameters featuring >1 RTW subtask. Data extraction and synthesis; standardised-mean-differences (SMDs) were calculated (pooled if replicated in >1 study) for each parameter. Consistency was determined if SMD95 %CIs included the zero-effect line. Results :Nine studies (n = 99) were included (40 ± 7.5yrs). Seven parameters were replicated in >1 study and subjected to meta-analysis (fixed-effect model). Two were consistent between sit-to-stand and sit-to-walk: flexion-momentum time (M(95 %CI) = 0.055(-0.423 to 0.533); p = 0.823) and peak whole-body-centre-of-mass vertical velocity (M(95 %CI)= -0.415(-0.898 to 0.069); p = 0.093); and centre-of-pressure to whole-body-centre-of-mass distance at toe-off (M(95 %CI)= -0.137(-0.712 to 0.439); p = 0.642) between gait-initiation and sit-to-walk. Another 20 parameters were consistent based on single-study SMDs. Significance :Consistent parameters might exist across RTW subtasks. However, the evidence is based on few studies with small samples and variable RTW protocols. Future studies designed to confirm consistency using a standardised RTW protocol are needed.

Background: Workers of various occupations often report Work Related Upper Quadrant Disorders (WRUQDs). Research has shown that associative factors for WRUQDs include psychosocial and environmental elements, gender and physical activity levels. To date no review has investigated whether physical activity participation is associated to the incidence or may predict the development of WRUQDs. Objective: To determine whether physical activity participation is associated with and/or predicts the development of Work Related Upper Quadrant Disorders (WRUQDs) Methods: A systematic review was conducted including searches of PubMed (MEDLINE), EMBASE and CINAHL from inception to March 31st 2017. Quantitative studies including any outcome measure of physical activity participation and its association with and/or prediction to WRUQDs were included. One reviewer conducted the search and two reviewers independently assessed eligibility and completed methodological quality assessment using a modified Downs and Black checklist. Data was analysed narratively. Results: Eight studies were eligible for inclusion in the final review. The quality of these ranged from moderate to high quality. Three studies reported nil statistical difference between physical activity participation and the risk of developing WRUQD. Three studies reported a negative and one study reported a positive association between physical activity participation and WRUQDs. One study reported that little or no physical exercise participation was a risk factor WRUQD. Conclusion: There is limited evidence for a negative association between physical activity participation and WRUQDs development. However this was not a consistent finding across all studies included. Further research is indicated in standardising diagnostic criteria and physical activity participation measurement in this patient population.

Background Diagnosis of chronic low back pain (CLBP) is traditionally predicated on identifying underlying pathological or anatomical causes, with treatment outcomes modest at best. Alternately, it is suggested that identification of underlying pain mechanisms with treatments targeted towards specific pain phenotypes may yield more success. Differentiation between nociceptive and neuropathic components of CLBP is problematic; evidence suggests that clinicians fail to identify a significant neuropathic component in many CLBP patients. The painDETECT questionnaire (PDQ) was specifically developed to identify occult but significant neuropathic components in individuals thought to have predominantly nociceptive pain. Methods Using the PDQ, we classified 50 CLBP patients into two distinct groups; those with predominantly nociceptive pain (Group 1) and those with a significant neuropathic component (Group 2). We characterised these two distinct CLBP sub-groups using a) questionnaire-based behavioural evaluation measuring pain-related function and quality of life, pain intensity and psychological well-being and b) sensory examination, using two-point and tactile threshold discrimination. Objective We sought to determine if differences in the pain phenotype of each CLBP sub-group would be reflected in sensory and behavioural group profiles. Results We report that Group 1 and Group 2 sub-groups demonstrate unique clinical profiles with significant differences in sensory tactile discrimination thresholds and in a wide range of behavioural domains measuring pain intensity, disability and psychological well-being. Conclusion We have demonstrated distinct clinical profiles for CLBP patient sub-groups classified by PDQ. Our results give diagnostic confidence in using the PDQ to characterise two distinct pain phenotypes in a heterogeneous CLBP population., Highlights • Identification of underlying CLBP pain phenotypes is challenging. • We used painDETECT to identify nociceptive and neuropathic CLBP subgroups. • We demonstrate unique sensory and behavioural clinical profiles for each group. • More accurate identification of CLBP pain phenotypes may improve treatment outcomes.

Background The pathophysiology of pain in Parkinson's disease (PD) is still poorly understood, although it is conceivable that supraspinal mechanisms may be responsible for pain generation and maintenance. Methods We examined brain functional and anatomical changes associated with persistent pain in 40 PD patients, 20 with persistent pain and 20 without pain. We also examined 15 pain-free healthy participants of similar age, gender, and cognitive state as a control group. We assessed pain by the King's Parkinson's Pain Scale, the Visual Analogue Scale for pain, and the Leeds Assessment for Neuropathic Symptoms and Sign. All patients underwent structural, diffusion tensor imaging, and resting-state functional MRI. We compared clinical characteristics, whole-brain cortical thickness, subcortical volumes, diffusion tensor imaging scalar measures, and functional connectivity by network based statistics. Results The group with PD and persistent pain showed significant thinning in the bilateral temporal pole, left-medial orbitofrontal cortex, bilateral superior and left-inferior parietal areas, pars orbicularis, and right superior frontal, posterior cingulated, and precentral cortex. There were no significant subcortical volume and white matter differences between PD subgroups. Functional MRI showed a decrease of brain activity in the left frontal inferior orbital in PD patients with persistent pain, with greater activity bilaterally in the cerebellum and in the right inferior temporal areas. Only PD patients with persistent pain showed an accumbens–hippocampus disconnection without white matter and subcortical alterations. Conclusions We showed that persistent pain in PD is associated with supraspinal structural and functional changes. We also highlighted the contribution of frontal, prefrontal, and insular areas in nociceptive modulation and accumbens–hippocampus disconnection. © 2016 International Parkinson and Movement Disorder Society.

BACKGROUND: Rising-to-walk is an everyday transitional movement task rarely employed in gait rehabilitation. Sit-to-walk (STW) and sit-to-stand-and-walk (STSW), where a pause separates sit-to-stand and gait-initiation (GI) represent extremes of rising-to-walk behaviour. Delayed GI can indicate pathological impairment but is also observed in healthy individuals. We hypothesise that healthy subjects express consistent biomechanical parameters, among others that differ, during successful rising-to-walk task performance regardless of behaviour. This study therefore sought to identify if any parameters are consistent between STW and STSW in health because they represent normal rise-to-walk performance independent of pause, and also because they represent candidate parameters sensitive enough to monitor change in pathology. METHODS: Ten healthy volunteers performed 5 trials of STW and STSW. Event timing, ground-reaction-forces (GRFs), whole-body-centre-of-mass (BCoM) displacement, and centre-of-pressure (CoP) to extrapolated BCoM (xCoM) distance (indicator of positional stability) up to the 3rd step were compared between-tasks with paired t-tests. For consistent parameters; agreement between-tasks was assessed using Bland-Altman analyses and minimal-detectable-change (MDC) calculations. RESULTS: Mean vertical GRFs, peak forward momentum and fluidity during rising; CoP-xCoM separation at seat-off, upright, GI-onset, and steps1-2; and forward BCoM velocity were all significantly greater in STW. In contrast, peak BCoM vertical momentum, flexion-momentum time, and 3rd step stability were consistent between tasks and yielded acceptable reliability. CONCLUSION: STW is a more challenging task due to the merging of rising with GI reflected by greater CoP-xCoM separation compared to STSW indicative of more positional instability. However, BCoM vertical momentum, flexion-momentum time, and step3 stability remained consistent in healthy individuals and are therefore candidates with which to monitor change in gait rehabilitation following pathology. Future studies should impose typical pause-durations observed in pathology upon healthy subjects to determine if the parameters we have identified remain consistent.

Osteoarthritis (OA) is a major cause of long-term disability (1). Traditionally characterized by structural degradation of one or more synovial joints, OA is typically associated with pain, swelling, and stiffness (2). Reduced manual dexterity and inability to perform tasks due to symptoms affect quality of life and ability to function independently (3). Levels of pain and disability experienced by patients often do not correspond to the level of tissue damage observed in the affected joints (4), suggesting involvement of central nervous system mechanisms in the generation of OA-related pain (5). Given the prevalence of OA and an increasingly aging population, there is a pressing need for more effective treatments (6,7). Many commonly prescribed medications are ill suited for long-term use due to side effects including tolerance, dependency, and gastrointestinal complications (8,9). While pain is always a personal experience and subject to multiple psychosocial factors, there has long been a desire to complement subjective reports with reliable markers of pain perception and treatment effectiveness (10,11). Neuroimaging methodologies offer the potential to meet these desires (12). Functional magnetic resonance imaging (fMRI) provides a safe, noninvasive, repeatable indirect measure of neural activity suitable for use in crossover trial designs (12). Reports have suggested that fMRI could demonstrate analgesic effects in populations of patients with clinical pain, adding value to conventional behavioral end points and facilitating decision-making early in drug development, reducing risk, development times, and cost (12). Experimental fMRI studies have provided useful insights into the neural mechanisms of drug action (for review, see ref.(13)). In order to fulfill this potential, fMRI must depict the neural correlates of the response to analgesics in patients experiencing persistent pain. Preliminary studies in OA have shown promise in establishing neural correlates of response to analgesics (14,15), but to date these studies have been underpowered or lacked appropriate placebo control. In this study we investigated the potential of fMRI as a “fit-for-purpose” measurement technique in development of analgesics for persistent pain. We sought to determine the ability of fMRI to detect changes in brain functioning following a 1-week course of naproxen in individuals with OA of the first carpometacarpal (CMC) joint. Naproxen is an established, effective nonsteroidal antiinflammatory drug (NSAID) labeled for treatment of OA-related symptoms in the UK (http://www.emc.medicines.org.uk). We aimed to detect naproxen-induced changes in brain activity using a functionally relevant task that evoked pain. We hypothesized that task-evoked brain activity would be reduced following administration of naproxen, compared to placebo. In particular, we hypothesized that a network of brain regions previously associated with pain perception would display significant reductions in activity following naproxen administration, during the task load that induced the highest rating of pain intensity.

Background: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy of the upper limb. Research has shown that associative factors for CTS include occupational and biomechanical elements, gender, and age. To date, no systematic review has been undertaken to determine specifically whether there are any psychosocial risk factors in developing CTS. The objective is to determine whether psychosocial factors are associated with and/or predict the development of CTS. Methods: A systematic review was conducted including searches of PubMed (MEDLINE), EMBASE, and CINAHL from inception to May 30, 2017. Quantitative studies must have investigated a minimum of 1 or more psychosocial factors—cognitive, affective, behavioral, vocational, or interpersonal processes (eg, social support)—and include a point or risk estimate. One reviewer conducted the search and 2 reviewers independently assessed eligibility and completed methodological quality assessment using a modified Downs and Black checklist. Data were analyzed narratively. Results: Six moderate- to high-quality studies were included in the final review. Five studies reported a positive association between psychosocial factors and CTS, where psychosocial factors were more in those who reported CTS. One study reported no positive or negative association with CTS development. Four studies reported a negative association between psychosocial factors and CTS, where psychosocial factors were less in those who reported CTS. Conclusions: There is limited evidence for a positive association between psychosocial factors and CTS. However, this was not a consistent finding across all included studies. Further research is indicated in standardizing CTS diagnostic criteria and investigating other working environments. Refereed/Peer-reviewed

Background Older adults live with multimorbidity including frailty and cognitive impairment often requiring hospitalization. While physical activity interventions (PAIs) are a normal rehabilitative treatment, their clinical effect in hospitalized older adults is uncertain. Objective To observe PAI dosing characteristics and determine their impact on clinical performance parameters. Design A single-site prospective observational cohort study in an older persons' unit. Subjects Seventy-five older persons' unit patients ≥65 years. Intervention PAI; therapeutic contact between physiotherapy clinician and patient. Measurements Parameters included changes in activities-of-daily-living (Barthel Index), handgrip strength, balance confidence, and gait velocity, measured between admission and discharge (episode). Dosing characteristics were PAI temporal initiation, frequency, and duration. Frailty/cognition status was dichotomized independently per participant yielding 4 subgroups: frail/nonfrail and cognitively-impaired/cognitively-unimpaired. Results Median (interquartile range) PAI initiation occurred after 2 days (1-4), frequency was 0.4 PAIs per day (0.3-0.5), and PAI duration per episode was 3.75 hours (1.8-7.2). All clinical parameters improved significantly across episodes: grip strength median (interquartile range) change, 2.0 kg (0.0-2.3) (P < .01); Barthel Index, 5 (3-8) (P < .01); gait velocity, 0.06 m.∙s−1 (0.06-0.16) (P < .01); and balance confidence, −3 (−6 to −1) (P < .01). Physical activity intervention dosing remained consistent within subgroups. While several moderate to large associations between amount of PAIs and change in clinical parameters were observed, most were within unimpaired subgroups. Conclusions PAI dosing is consistent. However, while clinical changes during hospital episodes are positive, more favourable responses to PAIs occur if patients are nonfrail/cognitively-unimpaired. Therefore, to deliver a personalized rehabilitation approach, adaptation of PAI dose based on patient presentation is desirable.

Perception is seen as a process that utilises partial and noisy information to construct a coherent understanding of the world. Here we argue that the experience of pain is no different; it is based on incomplete, multimodal information, which is used to estimate potential bodily threat. We outline a Bayesian inference model, incorporating the key components of cue combination, causal inference, and temporal integration, which highlights the statistical problems in everyday perception. It is from this platform that we are able to review the pain literature, providing evidence from experimental, acute, and persistent phenomena to demonstrate the advantages of adopting a statistical account in pain. Our probabilistic conceptualisation suggests a princ iples-based view of pain, explaining a broad range of experimental and clinical findings and making testable predictions. Refereed/Peer-reviewed

Background:Gait-initiation onset (GI-onset) during sit-to-walk (STW) is commonly defined by mediolateral ground-reaction-force (xGRF) rising and crossing a threshold pre-determined from sitto- stand peak xGRF. However, after stroke this method [xGRFthresh] lacks validity due to impaired STW performance. Instead, methodologies based upon instance of swing-limb maximum-vertical-GRF [vGRFmaxSWING], maximum-xGRF [xGRFmax], and swing-limb heel-off [firstHEELoff] can be applied, although their validity is unclear. Therefore, we determined these methodologies' validity by revealing the shortest transition-time (seat-off-GIonset), their utility in routinely estimating GI-onset, and whether they exhibited satisfactory intra-subject reliability. Methods:Twenty community-dwelling stroke (60 (SD 14) years), and twenty-one age-matched healthy volunteers (63 (13) years) performed 5 standardised STW trials with 2 force-plates and optical motion-tracking. Transition-time differences across-methods were assessed using Friedman tests with post-hoc pairwise-comparisons. Within-method single-measure intra-subject reliability was determined using ICC3,1 and standard errors of measurement (SEMs). Results:In the healthy group, median xGRFthresh transition-time was significantly shorter than xGRFmax (0.183s). In both the healthy and stroke groups, xGRFthresh transition-times (0.027s, 0.695s respectively) and vGRFmaxSWING (0.080s, 0.522s) were significantly shorter than firstHEELoff (0.293s, 1.085s) (pConclusion:The firstHEELoff method yielded significantly longer transition-times. The xGRFthresh method failed to routinely produce an estimation of GI-onset estimation. Thus, with all methods exhibiting low, yet comparable intra-subject repeatability, averaged xGRFmax or vGRFmaxSWING repeated-measures are recommended to estimate GI-onset for both healthy and community-dwelling stroke individuals.

Arterial spin labelling (ASL) is increasingly being applied to study the cerebral response to pain in both experimental human models and patients with persistent pain. Despite its advantages, scanning time and reliability remain important issues in the clinical applicability of ASL. Here we present the test–retest analysis of concurrent pseudo-continuous ASL (pCASL) and visual analogue scale (VAS), in a clinical model of on-going pain following third molar extraction (TME). Using ICC performance measures, we were able to quantify the reliability of the post-surgical pain state and ΔCBF (change in CBF), both at the group and individual case level. Within-subject, the inter- and intra-session reliability of the post-surgical pain state was ranked good-to-excellent (ICC > 0.6) across both pCASL and VAS modalities. The parameter ΔCBF (change in CBF between pre- and post-surgical states) performed reliably (ICC > 0.4), provided that a single baseline condition (or the mean of more than one baseline) was used for subtraction. Between-subjects, the pCASL measurements in the post-surgical pain state and ΔCBF were both characterised as reliable (ICC > 0.4). However, the subjective VAS pain ratings demonstrated a significant contribution of pain state variability, which suggests diminished utility for interindividual comparisons. These analyses indicate that the pCASL imaging technique has considerable potential for the comparison of within- and between-subjects differences associated with pain-induced state changes and baseline differences in regional CBF. They also suggest that differences in baseline perfusion and functional lateralisation characteristics may play an important role in the overall reliability of the estimated changes in CBF. Repeated measures designs have the important advantage that they provide good reliability for comparing condition effects because all sources of variability between subjects are excluded from the experimental error. The ability to elicit reliable neural correlates of on-going pain using quantitative perfusion imaging may help support the conclusions derived from subjective self-report., Highlights • Test-retest reliability of pCASL is considered in a post-surgical pain model. • Pain-state and ∆CBF measurements were reliable at the group and individual level. • Single or average baseline measurements improve reliability of ∆CBF. • pCASL is a reliable technique for detecting cerebral responses to on-going pain.

© 2016 Journal of Visualized Experiments.Individuals with sensorimotor pathology e.g., stroke have difficulty executing the common task of rising from sitting and initiating gait (sit-to-walk: STW). Thus, in clinical rehabilitation separation of sit-to-stand and gait initiation - termed sit-to-stand-and-walk (STSW) - is usual. However, a standardized STSW protocol with a clearly defined analytical approach suitable for pathological assessment has yet to be defined. Hence, a goal-orientated protocol is defined that is suitable for healthy and compromised individuals by requiring the rising phase to be initiated from 120% knee height with a wide base of support independent of lead limb. Optical capture of three-dimensional (3D) segmental movement trajectories, and force platforms to yield two-dimensional (2D) center-of-pressure (COP) trajectories permit tracking of the horizontal distance between COP and whole-body-center-of-mass (BCOM), the decrease of which increases positional stability but is proposed to represent poor dynamic postural control. BCOM-COP distance is expressed with and without normalization to subjects' leg length. Whilst COP-BCOM distances vary through STSW, normalized data at the key movement events of seat-off and initial toe-off (TO1) during steps 1 and 2 have low intra and inter subject variability in 5 repeated trials performed by 10 young healthy individuals. Thus, comparing COP-BCOM distance at key events during performance of an STSW paradigm between patients with upper motor neuron injury, or other compromised patient groups, and normative data in young healthy individuals is a novel methodology for evaluation of dynamic postural stability.

OBJECTIVE: The experience of chronic pain critically alters one's ability to interact with their environment. One fundamental issue that has received little attention however, is whether chronic pain disrupts how one perceives their environment in the first place. The Economy of Action hypothesis purports that the environment is spatially scaled according to the ability of the observer. Under this hypothesis it has been proposed that the perception of the world is different between those with and without chronic pain. Such a possibility has profound implications for the investigation and treatment of pain. The present investigation looked to test the application of this hypothesis to a heterogeneous chronic pain population.METHODS: Chronic pain sufferers (36; 27F) and matched pain-free controls were recruited. Each participant was required to judge the distance to a series of target cones, to which they were to subsequently walk. In addition, at each distance, participants used numerical rating scales to indicate their perceived effort and perceived pain associated with the distance presented.RESULTS: Our findings do not support the Economy of Action hypothesis: there were no significant differences in distance estimates between the chronic pain group and pain-free controls (F(1,60)=0.927; P=0.340). In addition, we found no predictive relationship in the chronic pain group between anticipated pain and estimated distance (F(1,154)=0.122, P=0.727), nor anticipated effort=1.171, P=0.281) and estimated distance (F(1,154)=1.171, P=0.281).DISCUSSION: The application of the Economy of Action hypothesis and the notion of spatial perceptual scaling as a means to assess and treat the experience of chronic pain are unfounded.

The pathophysiology of pain in Parkinson's disease (PD) is still poorly understood, although it is conceivable that supraspinal mechanisms may be responsible for pain generation and maintenance.We examined brain functional and anatomical changes associated with persistent pain in 40 PD patients, 20 with persistent pain and 20 without pain. We also examined 15 pain-free healthy participants of similar age, gender, and cognitive state as a control group. We assessed pain by the King's Parkinson's Pain Scale, the Visual Analogue Scale for pain, and the Leeds Assessment for Neuropathic Symptoms and Sign. All patients underwent structural, diffusion tensor imaging, and resting-state functional MRI. We compared clinical characteristics, whole-brain cortical thickness, subcortical volumes, diffusion tensor imaging scalar measures, and functional connectivity by network based statistics.The group with PD and persistent pain showed significant thinning in the bilateral temporal pole, left-medial orbitofrontal cortex, bilateral superior and left-inferior parietal areas, pars orbicularis, and right superior frontal, posterior cingulated, and precentral cortex. There were no significant subcortical volume and white matter differences between PD subgroups. Functional MRI showed a decrease of brain activity in the left frontal inferior orbital in PD patients with persistent pain, with greater activity bilaterally in the cerebellum and in the right inferior temporal areas. Only PD patients with persistent pain showed an accumbens-hippocampus disconnection without white matter and subcortical alterations.We showed that persistent pain in PD is associated with supraspinal structural and functional changes. We also highlighted the contribution of frontal, prefrontal, and insular areas in nociceptive modulation and accumbens-hippocampus disconnection. © 2016 International Parkinson and Movement Disorder Society.

Objective: To determine the factors associated with physical activity participation in adults with chronic cervical spine pain. Methods: A systematic review was conducted including searches of PubMed (MEDLINE), EMBASE and CINAHL from inception to June 12th, 2016. Grey literature and reference checking was also undertaken. Quantitative studies including factors related to physical activity participation in adults with chronic cervical spine pain were included. Two independent authors conducted the searches, extracted data and completed methodological quality assessment. Results: A total of seven studies met the selection criteria, however, four papers were finally included in the final review. A modified Downs and Black criteria was used to assess methodological quality, each study included was classed as moderate quality. A total of six factors were assessed against physical activity participation for people with chronic neck pain. These included: pain, fear of movement, smoking habits, socioeconomic status, gender, leisure and work time habits. A significant relationship was demonstrated between pain, leisure and work time habits and physical activity. Subjects were less likely to participate in physical activity if they were in pain. Subjects with neck pain were less likely to participate in physical activity in their leisure and work time. Conclusion: This review, based on a small number of heterogeneous studies demonstrated key factors that are likely to affect physical activity in people with chronic neck pain, most notably, pain levels, leisure and work habits. This review suggests that more in-depth, high quality studies are required to fully understand the impact of chronic pain on physical activity. Systematic review registration number: PROSPERO CRD42015027970. Refereed/Peer-reviewed

While neuroimmune interactions are increasingly recognized as important in nociceptive processing, the nature and functional significance of these interactions is not well defined. There are multiple reports that the activation of spinal microglia is a critical event in the generation of neuropathic pain behaviors but the mediators of this activation remain disputed. Here we show that the chemokine CCL2, produced by both damaged and undamaged primary sensory neurons in neuropathic pain states in rats, is released in an activity dependent manner from the central terminals of these fibres. We also demonstrate that intraspinal CCL2 in naïve rats leads to activation of spinal microglia and neuropathic pain-like behavior. An essential role for spinal CCL2 is demonstrated by the inhibition of neuropathic pain behavior and microglial activation by a specific neutralising antibody to CCL2 administered intrathecally. Thus, the neuronal expression of CCL2 provides a mechanism for immune activation, which in turn regulates the sensitivity of pain signaling systems in neuropathic pain states.

© 2016 Elsevier B.V.Introduction: Sit-to-walk (STW) is a common transitional motor task not usually included in rehabilitation. Typically, sit-to-stand (STS), pause, then gait initiation (GI) before walking is used, which we term sit-to-stand-and-walk (STSW). Separation between centre-of-pressure (COP) and whole-body centre-of-mass (BCOM) during GI is associated with dynamic postural stability. Rising from seats higher than knee-height (KH) is more achievable for patients, but whether this and/or lead-limb significantly affects task dynamics is unclear. This study tested whether rising from seat-heights and lead-limb affects STW and STSW task dynamics in young healthy individuals. Methods: Ten (5F) young (29 ± 7.7 years) participants performed STW and STSW from a standardised position. Five trials of each task were completed at 100 and 120%KH leading with dominant and non-dominant legs. Four force-plates and optical motion capture delineated key movement events and phases with effect of seat-height and lead-limb determined by 2-way ANOVA within tasks. Results: At 120%KH, lower peak vertical ground-reaction-forces (vGRFs) and vertical BCOM velocities were observed during rising irrespective of lead-limb. No other parameters differed between seat-heights or lead-limbs. During GI in STSW there was more lateral, and less posterior, COP excursion than expected. Conclusion: Reduction in vGRFs and velocity during rising at 120%KH is consistent with reduced effort in young healthy individuals and is likely therefore to be an appropriate seat-height for patients. Lead-limb had no effect upon STSW or STW parameters suggesting that normative data independent of lead-limb can be utilised to monitor motor rehabilitation should differences be observed in patients. STSW should be considered an independent movement transition.

Pain is an experience that powerfully influences the way we interact with our environment. What is less clear is the influence that pain has on the way we perceive our environment. We investigated the effect that the anticipation of experimental pain (THREAT) and its relief (RELIEF) has on the visual perception of space. Eighteen (11F) healthy volunteers estimated the distance to alternating THREAT and RELIEF stimuli that were placed within reachable space. The results determined that the estimated distance to the THREAT stimulus was significantly underestimated in comparison to the RELIEF stimulus. We conclude that pain-evoking stimuli are perceived as closer to the body than otherwise identical pain-relieving stimuli, an important consideration when applied to our decisions and behaviors in relation to the experience of pain. Refereed/Peer-reviewed

Background There has been a widespread call for an ethics in the management of patients with chronic pain which is patient centered and takes into account the lived experience of the patient. It has been argued in literature that current “duty” or principlist-based models of ethics (so-called 3rd person ethics) have not adequately addressed the needs of either patients or practitioners in this area. Method Two strands of literature within phenomenology were reviewed: the literature of interpretative phenomenological analysis and the study of the lived experience of the person with chronic pain; and the contribution of phenomenology in neo-Aristotelian virtue ethics (1st person ethics). Findings Patients experience chronic pain in existential and moral terms in addition to their biomedical issues, facing dilemmas in understanding their own self-identity and in attempting to recover a sense of moral worth and agency. Discussion We outline a patient-centered ethics to underpin contemporary collaborative, multimodal approaches in the management of chronic pain. We firstly describe an agency-oriented, neo-Aristotelian 1st person ethics and then outline a hermeneutic relationship with extant “duty-based,” 3rd person bioethics. The utility of the ethics model we propose (the ethical reasoning bridge) lies in its capacity for developing a sense of moral agency for both practitioner and patient, resonating with the current emphasis of seeking active engagement of patients in management.

Pain is fundamental to survival, as are our perceptions of the environment. It is often assumed that we see our world as a read-out of the sensory information that we receive; yet despite the same physical makeup of our surroundings, individuals perceive differently. What if we ‘‘see’’ our world differently when we experience pain? Until now, the causal effect of experimental pain on the perception of an external stimulus has not been investigated. Eighteen (11 female) healthy volunteers participated in this randomised repeated-measures experiment, in which participants estimated the distance to a switch placed on the table in front of them. We varied whether or not the switch would instantly stop a stimulus, set to the participant’s pain threshold, being delivered to their hand, and whether or not they were required to reach for the switch. The critical result was a strong interaction between reaching and pain [F(1, 181) = 4.8, P = 0.03], such that when participants experienced pain and were required to reach for a switch that would turn off the experimental stimulus, they judged the distance to that switch to be closer, as compared to the other 3 conditions (mean of the true distance 92.6%, 95% confidence interval 89.7%–95.6%). The judged distance was smaller than estimates in the other 3 conditions (mean ± SD difference >5.7% ± 2.1%, t(181) >3.5, P < 0.01 for all 3 comparisons). We conclude that the perception of distance to an object is modulated by the behavioural relevance of the object to ongoing pain. Refereed/Peer-reviewed

Refereed/Peer-reviewed

Nicht-Opioide wie nicht-steroidale Antiphlogistika (NSAID) sind die am haufigsten verwendete Analgetika-Klasse. Es ist bekannt, dass Cyclooxygenasehemmer sowohl peripher als auch zentral einen antihyperalgetischen Effekt ausuben – man nimmt an, dass der Hauptanteil des klinischen Effekts hierbei zentral vermittelt wird.

As a mechanisms-based classification of pain 'central sensitisation pain' (CSP) refers to pain arising from a dominance of neurophysiological dysfunction within the central nervous system. Symptoms and signs associated with an assumed dominance of CSP in patients attending for physiotherapy have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of CSP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol. Patients' pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist specifying the presence or absence of various clinical criteria. A binary logistic regression analysis with Bayesian model averaging identified a cluster of three symptoms and one sign predictive of CSP, including: 'Disproportionate, non-mechanical, unpredictable pattern of pain provocation in response to multiple/non-specific aggravating/easing factors', 'Pain disproportionate to the nature and extent of injury or pathology', 'Strong association with maladaptive psychosocial factors (e.g. negative emotions, poor self-efficacy, maladaptive beliefs and pain behaviours)' and 'Diffuse/non-anatomic areas of pain/tenderness on palpation'. This cluster was found to have high levels of classification accuracy (sensitivity 91.8%, 95% confidence interval (CI): 84.5-96.4; specificity 97.7%, 95% CI: 95.6-99.0). Pattern recognition of this empirically-derived cluster of symptoms and signs may help clinicians identify an assumed dominance of CSP in patients with low back pain disorders in a way that might usefully inform their management.

As a mechanisms-based classification of pain 'nociceptive pain' (NP) refers to pain attributable to the activation of the peripheral receptive terminals of primary afferent neurones in response to noxious chemical, mechanical or thermal stimuli. The symptoms and signs associated with clinical classifications of NP have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of NP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol after which their pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist indicating the presence/absence of various symptoms and signs. A regression analysis identified a cluster of seven clinical criteria predictive of NP, including: 'Pain localised to the area of injury/dysfunction', 'Clear, proportionate mechanical/anatomical nature to aggravating and easing factors', 'Usually intermittent and sharp with movement/mechanical provocation; may be a more constant dull ache or throb at rest', and the absence of 'Pain in association with other dysesthesias', 'Night pain/disturbed sleep', 'Antalgic postures/movement patterns' and 'Pain variously described as burning, shooting, sharp or electric-shock-like'. This cluster was found to have high levels of classification accuracy (sensitivity 90.9%, 95% CI: 86.6-94.1; specificity 91.0%, 95% CI: 86.1-94.6). Pattern recognition of this empirically-derived cluster of symptoms and signs may help clinicians identify an assumed dominance of NP mechanisms in patients with low back pain disorders.

As a mechanisms-based classification of pain 'peripheral neuropathic pain' (PNP) refers to pain arising from a primary lesion or dysfunction in the peripheral nervous system. Symptoms and signs associated with an assumed dominance of PNP in patients attending for physiotherapy have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of PNP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol. Patients' pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist specifying the presence or absence of various clinical criteria. A binary logistic regression analysis with Bayesian model averaging identified a cluster of two symptoms and one sign predictive of PNP, including: 'Pain referred in a dermatomal or cutaneous distribution', 'History of nerve injury, pathology or mechanical compromise' and 'Pain/symptom provocation with mechanical/movement tests (e.g. Active/Passive, Neurodynamic) that move/load/compress neural tissue'. This cluster was found to have high levels of classification accuracy (sensitivity 86.3%, 95% CI: 78.0-92.3; specificity 96.0%, 95% CI: 93.4-97.8; diagnostic odds ratio 150.9, 95% CI: 69.4-328.1). Pattern recognition of this empirically-derived cluster of symptoms and signs may help clinicians identify an assumed dominance of PNP mechanisms in patients with low back pain disorders in a way that might usefully inform subsequent patient management.

Objective Increasing evidence suggests a central nervous system (CNS) component underpinning persistent pain disease states. This study was undertaken to determine regional cerebral blood flow (rCBF) changes representing ongoing pain experienced by patients with painful osteoarthritis (OA) of the carpometacarpal (CMC) joint and to examine rCBF variability across sessions. We used pulsed continuous arterial spin labeling (pCASL), a perfusion magnetic resonance imaging (MRI) technique. Methods The study included 16 patients with CMC OA and 17 matched controls. Two pCASL scans and numerical rating scale (NRS) estimates of ongoing pain were acquired in each of two identical sessions. Voxelwise general linear model analyses were performed to determine rCBF differences between OA and control groups, rCBF differences between sessions within each group, and whether sessionwise rCBF differences were related to variability in perceived ongoing pain. Results In the OA group, rCBF increases representing ongoing pain were identified in the primary and secondary somatosensory, insula, and cingulate cortices; thalamus; amygdala; hippocampus; and dorsal midbrain/pontine tegmentum, including the periaqueductal gray/nucleus cuneiformis. Sessionwise rCBF differences in the OA group in the postcentral, rostral/subgenual cingulate, mid/anterior insula, prefrontal, and premotor cortices were related to changes in perceived ongoing pain. No significant sessionwise rCBF differences were observed in controls. Conclusion This is the first quantitative endogenous perfusion MRI study of the cerebral representation of ongoing, persistent pain due to OA. Observed rCBF changes potentially indicate dysregulated CNS appraisal and modulation of pain, most likely the maladaptive neuroplastic sequelae of living with painful OA. Understanding the neural basis of ongoing pain is likely to be important in developing novel treatment strategies.

Background Sarcoidosis is a polygenic disease with diverse phenotypic presentations characterized by an abnormal antigen-mediated Th1 type immune response. At present, progress towards understanding sarcoidosis disease mechanisms and the development of novel treatments is limited by constraints attendant to conducting human research in a rare disease in the absence of relevant animal models. We sought to develop a computational model to enhance our understanding of the pathological mechanisms of and predict potential treatments of sarcoidosis. Methodology/Results Based upon the literature, we developed a computational model of known interactions between essential immune cells (antigen-presenting macrophages, effector and regulatory T cells) and cytokine mediators (IL-2, TNFα, IFNγ) of granulomatous inflammation during sarcoidosis. The dynamics of these interactions are described by a set of ordinary differential equations. The model predicts bistable switching behavior which is consistent with normal (self-limited) and “sarcoidosis-like” (sustained) activation of the inflammatory components of the system following a single antigen challenge. By perturbing the influence of model components using inhibitors of the cytokine mediators, distinct clinically relevant disease phenotypes were represented. Finally, the model was shown to be useful for pre-clinical testing of therapies based upon molecular targets and dose-effect relationships. Conclusions/Significance Our work illustrates a dynamic computer simulation of granulomatous inflammation scenarios that is useful for the investigation of disease mechanisms and for pre-clinical therapeutic testing. In lieu of relevant in vitro or animal surrogates, our model may provide for the screening of potential therapies for specific sarcoidosis disease phenotypes in advance of expensive clinical trials.

There is increasing evidence that chronic pain problems are characterised by alterations in brain structure and function. Chronic back pain is no exception. There is a growing sentiment, with accompanying theory, that these brain changes contribute to chronic back pain, although empirical support is lacking. This paper reviews the structural and functional changes of the brain that have been observed in people with chronic back pain. We cast light on the clinical implications of these changes and the possibilities for new treatments but we also advise caution against concluding their efficacy in the absence of solid evidence to this effect. National Health & Medical Research Council of Australia.

Damage to the peripheral nervous system often leads to chronic neuropathic pain characterized by spontaneous pain and an exaggerated response to painful and/or innocuous stimuli. This pain condition is extremely debilitating and usually difficult to treat. Although inflammatory and neuropathic pain syndromes are often considered distinct entities, emerging evidence belies this strict dichotomy. Inflammation is a well-characterized phenomenon, which involves a cascade of different immune cell types, such as mast cells, neutrophils, macrophages, and T lymphocytes. In addition, these cells release numerous compounds that contribute to pain. Recent evidence suggests that immune cells play a role in neuropathic pain in the periphery. In this review we identify the different immune cell types that contribute to neuropathic pain in the periphery and release factors that are crucial in this particular condition.

The effect of ice accretion on a 1/12-scale complete aircraft model of a business jet was studied in a rotary-balance wind tunnel. Three types of ice accretions were considered: ice protection system failure shape, pre-activation roughness, and runback shapes that form downstream of the thermal ice protection system. The results were compared with those from a 1/12-scale semi-span wing of the same aircraft at similar Reynolds number. The data showed that the full aircraft and the semi-span wing models showed similar characteristics, especially post stall behavior under iced configuration. However, there were also some discrepancies, such as the magnitude in the reductions in the maximum lift coefficient. Most of the ice-induced effects were limited to longitudinal forces. Rotational and forced oscillation studies showed that the effects of ice on lateral forces were relatively minor.

i ,I:... ,;: ,,,_ . I :‘,.,,. ..;, !, .’ :,. ,“. . ‘-g ; Introductions !;; ..:, ,>+‘. ,:. F -8 Recent developments and fu&e plans have prompted Cessna Aircraft Company to evaluate several mature and emerging CFD methodologies. The state of the art for CFD codes hasbeen stead@ advancing for many years. During this time, several methods have made the transition from use in a research environment, to use in an operational environment There are additional requirements which must be placed on a method before it is suitable for the latter use.