Nociceptive, neuropathic, or nociplastic low back pain? The low back pain phenotyping (BACPAP) consortium's international and multidisciplinary consensus recommendations.

The potential to classify low back pain as being characterised by dominant nociceptive, neuropathic, or nociplastic mechanisms is a clinically relevant issue. Preliminary evidence suggests that these low back pain phenotypes might respond differently to treatments; however, more research must be done before making specific recommendations. Accordingly, the low back pain phenotyping (BACPAP) consortium was established as a group of 36 clinicians and researchers from 13 countries (five continents) and 29 institutions, to apply a modified Nominal Group Technique methodology to develop international and multidisciplinary consensus recommendations to provide guidance for identifying the dominant pain phenotype in patients with low back pain, and potentially adapt pain management strategies. The BACPAP consortium's recommendations are also intended to provide direction for future clinical research by building on the established clinical criteria for neuropathic and nociplastic pain. The BACPAP consortium's consensus recommendations are a necessary early step in the process to determine if personalised pain medicine based on pain phenotypes is feasible for low back pain management. Therefore, these recommendations are not ready to be implemented in clinical practice until additional evidence is generated that is specific to these low back pain phenotypes.

Patient-related barriers and enablers to the implementation of high-value physiotherapy for chronic pain: a systematic review.

OBJECTIVE: To identify and synthesize patient-related barriers to and enablers of the implementation of high-value physiotherapy (HVP) for chronic pain. Furthermore, to review what patient-related interventions have been used to facilitate the implementation of HVP for chronic pain, as well as their efficacy. METHODS: We systematically searched the APA PsycInfo, Embase, CINAHL, Medline, Scopus, and PEDro databases for peer-reviewed studies (published in English) of adults with chronic pain. We used the Theoretical Domains Framework of behavior change to synthesize identified themes relating to barriers and enablers. Outcomes from studies reporting on interventions were also qualitatively synthesized. RESULTS: Fourteen studies reported on barriers and enablers, 8 of which related to exercise adherence. Themes common to barriers and enablers included perceived efficacy of treatment, interrelationship with the physiotherapist, exercise burden, and the patient's understanding of exercise benefits. Other barriers included fear of movement, fragmented care, and cost. Ten studies explored interventions, 9 of which aimed to improve exercise adherence. Of these, evidence from 4 randomized controlled trials of technology-based interventions demonstrated improved exercise adherence among intervention groups compared with controls. CONCLUSION: Patients with chronic pain experience barriers to HVP, including their beliefs, the nature of their interaction with their physiotherapist, perceived treatment efficacy, and cost. Enablers include rapport with their physiotherapist, achievable exercises, and seamless cost-effective care. Technology-based interventions have demonstrated effectiveness at increasing exercise adherence. Our findings suggest that interventions seeking to enhance implementation of HVP need to consider the multifactorial barriers experienced by patients with chronic pain. STUDY REGISTRATION: Open Science Framework (https://doi.org/10.17605/OSF.IO/AYGZV).

Exercise Therapy for Chronic Neck Pain: Tailoring Person-Centred Approaches within Contemporary Management.

Exercise therapy is considered the best evidence-based approach for managing chronic neck pain. However, the implementation of exercise therapy presents several challenges. Systematic reviews indicate that it has modest effectiveness, while clinical practice guidelines offer limited guidance on the exercise parameters required to optimise clinical outcomes. Moreover, recommendations often fail to differentiate between different types of neck pain. This article addresses the challenges associated with the prescription of exercise for chronic neck pain and provides recommendations for exercise therapy specific to chronic nociceptive, neuropathic, and nociplastic neck pain. The goal of this article is to facilitate the implementation of high-value evidence-based exercise therapy for these distinct types of chronic neck pain with the aim to improve its outcomes and to reduce the related individual and societal burdens.

Effectiveness of combined surgical and exercise-based interventions following primary traumatic anterior shoulder dislocation: a systematic review and meta-analysis.

OBJECTIVE: To investigate the effectiveness, risk of recurrence and return to activity (RTA) of surgery combined with exercise-based interventions (EBI) versus EBI alone after traumatic anterior shoulder dislocation (ASD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Systematic literature search (MEDLINE, Web of Science, Scopus, Google Scholar). ELIGIBILITY: Studies focused on EBI or EBI as a part of postoperative care for adults with an ASD, written in English, and published after 1990. We excluded diagnostic, assessment-based studies on individuals experiencing recurrent shoulder dislocations, concomitant shoulder injury, animal or cadaveric studies. Primary outcomes were dislocation RTA. Secondary outcomes were self-reported outcome measures, strength and range of motion. Random-effects meta-analysis was used to estimate the effect of EBI (SMD; Hedges' g, RR). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the certainty of evidence. RESULTS: Sixty studies were included (n=3598); seven were meta-analysed (n=345). The mean age of participants in the included studies was 26.71±9.19 and 56% of those included were male. Of the 60 studies included in the systematic review, 29 were fair quality (48.3%), 15 studies were good quality (25%) and 16 studies were poor quality (26.7%), (k=0.66). Individuals who underwent EBI alone were 2.03 times more likely to experience recurrent instability than individuals who underwent EBI in conjunction with surgery (RR 2.03, 95% CI 1.03 to 3.97). Individuals who underwent EBI with surgery appeared 1.81 times more likely to RTA than those who underwent EBI alone, although results were not statistically significant (RR 1.81, 95% CI 0.96 to 3.43). CONCLUSIONS: Surgery combined with EBI is more effective in reducing the risk of recurrence and possibly increasing RTA than EBI alone after traumatic ASD.

Differential Structural Brain Changes Between Responders and Nonresponders After Physical Exercise Therapy for Chronic Nonspecific Neck Pain.

OBJECTIVES: Physical exercise therapy is effective for some people with chronic nonspecific neck pain but not for others. Differences in exercise-induced pain-modulatory responses are likely driven by brain changes. We investigated structural brain differences at baseline and changes after an exercise intervention. The primary aim was to investigate changes in structural brain characteristics after physical exercise therapy for people with chronic nonspecific neck pain. The secondary aims were to investigate (1) baseline differences in structural brain characteristics between responders and nonresponders to exercise therapy, and (2) differential brain changes after exercise therapy between responders and nonresponders. MATERIALS AND METHODS: This was a prospective longitudinal cohort study. Twenty-four participants (18 females, mean age 39.7 y) with chronic nonspecific neck pain were included. Responders were selected as those with ≥20% improvement in Neck Disability Index. Structural magnetic resonance imaging was obtained before and after an 8-week physical exercise intervention delivered by a physiotherapist. Freesurfer cluster-wise analyses were performed and supplemented with an analysis of pain-specific brain regions of interest. RESULTS: Various changes in grey matter volume and thickness were found after the intervention, for example, frontal cortex volume decreased (cluster-weighted P value = 0.0002, 95% CI: 0.0000-0.0004). We found numerous differences between responders and nonresponders, most notably, after the exercise intervention bilateral insular volume decreased in responders, but increased in nonresponders (cluster-weighted P value ≤ 0.0002). DISCUSSION: The brain changes found in this study may underpin clinically observed differential effects between responders and nonresponders to exercise therapy for people with chronic neck pain. Identification of these changes is an important step toward personalized treatment approaches.

The effects of physical exercise on structural, functional, and biochemical brain characteristics in individuals with chronic whiplash-associated disorder: A pilot randomized clinical trial.

BACKGROUND: Exercise for people with whiplash associated disorder (WAD) induces hypoalgesic effects in some, but hyperalgesic effects in others. We investigated the exercise-induced neurobiological effects of aerobic and strengthening exercise in individuals with chronic WAD. METHODS: Sixteen participants (8 WAD, 8 pain-free [CON]) were randomised to either aerobic or strengthening exercise. MRI for brain morphometry, functional MRI for brain connectivity, and magnetic resonance spectroscopy for brain biochemistry, were used at baseline and after the 8-week intervention. RESULTS: There were no differences in brain changes between exercise groups in either the WAD or CON group, therefore aerobic and strengthening data were combined to optimise sample size. After the exercise intervention, the CON group demonstrated increased cortical thickness (left parahippocampus: mean difference = 0.04, 95% CI = 0.07-0.00, p = 0.032; and left lateral orbital frontal cortex: mean difference = 0.03, 95% CI = 0.00-0.06, p = 0.048). The WAD group demonstrated an increase in prefrontal cortex (right medial orbital frontal) volume (mean difference = 95.57, 95% CI = 2.30-192.84, p = 0.046). Functional changes from baseline to follow-up between the default mode network and the insula, cingulate cortex, temporal lobe, and somatosensory and motor cortices, were found in the CON group, but not in the WAD group. There were no changes post-exercise in brain biochemistry. CONCLUSION: Aerobic and strengthening exercises did not exert differential effects on brain characteristics, however differences in structural and functional changes were found between WAD and CON groups. This suggests that an altered central pain modulatory response may be responsible for differential effects of exercise in individuals with chronic WAD.

A Shared Genetic Signature for Common Chronic Pain Conditions and its Impact on Biopsychosocial Traits.

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.

Exercise-induced hypoalgesic effects of different types of physical exercise in individuals with neck pain: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the exercise-induced hypoalgesic (EIH) effects of different types of physical exercise in individuals with neck pain. DESIGN: Systematic review with meta-analysis. LITERATURE SEARCH: An electronic search of six databases was completed to include studies assessing EIH effects on neck pain. STUDY SELECTION CRITERIA: Randomized controlled trials, controlled trials, and observational studies that assessed before and immediate after-effects of a single session of physical exercise in people with neck pain were included. Two reviewers independently screened records, extracted outcomes, assessed the risk of bias, and rated the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. DATA SYNTHESIS: EIH is characterized by increased pain threshold, pain tolerance, and/or decreased sensitivity to painful stimuli or unpleasantness, which may last up to 30 min after a single bout of exercise. EIH is usually measured with quantitative sensory testing (QST) and is mostly taken as the difference between pre- and postexercise pressure pain threshold (PPT). Data were pooled and analyzed using a fixed-effect meta-analysis. RESULTS: Eleven articles were included in this review; nine with low risk of bias and two with some concerns about the risk of bias. Three studies with chronic whiplash-associated disorders (WAD) were included in the meta-analysis; isometric exercise had a larger EIH effect at the local testing site compared with submaximal aerobic exercises (MD = -0.21, [95% CI = -0.43, 0.00], p = 0.05, I2  = 92%), submaximal aerobic and isometric exercises had equal EIH effects at the remote testing site (MD = 0.01, [95% CI = -0.33, 0.35], p = 0.95, I2  = 0%), and submaximal aerobic exercises exerted comparably larger EIH effect at the remote testing site than local testing site (MD = -0.01, [95% CI = -0.20, 0.18], p = 0.93, I2  = 56%). The certainty of evidence (GRADE) for these analyses was low to very low. According to the descriptive analysis of the studies of chronic nonspecific neck pain, isometric and range of motion (ROM) exercises have shown EIH effects. Active stretching exercises have illustrated contradictory effects. CONCLUSION: Isometric and ROM exercises exerted hypoalgesia at local and remote sites. A larger EIH effect following submaximal aerobic exercises was exerted at the remote testing site compared with the local site.

The effectiveness of aerobic versus strengthening exercise therapy in individuals with chronic whiplash-associated disorder: a randomised single case experimental design study.

PURPOSE: Recent RCTs and meta-analyses compare the effectiveness of different types of exercise for chronic whiplash associated disorder (WAD). This study aimed to verify whether the results of these studies translate to statistically significant and clinically meaningful effects in individual participants. MATERIALS AND METHODS: A series of replicated randomised single case experimental design studies (SCEDs) with A-B design (A: baseline, B: intervention). Eight participants with chronic WAD (8 female, mean [SD] age 47 [10] years) were randomised into one of four baseline durations (5, 8, 11, and 14 days) and to one of two eight-week exercise interventions (aerobic or strengthening). Daily measures of pain intensity, bothersomeness, and interference were collected during the baseline phase and the intervention phase. RESULTS: Visual analyses indicated that three participants in the aerobic exercise group meaningfully improved. No improvements were found in the strengthening group. Effect sizes favoured the aerobic exercise group, yet randomisation tests of pooled effects did not show a difference in between-intervention effectiveness. CONCLUSION: Contrary to our expectations, three out of four participants were nearly pain-free at the end of the aerobic exercise intervention, whereas none of the participants in the strengthening group improved meaningfully. This suggests that aerobic exercise may be favourable for WAD.Implications for RehabilitationOur results suggest that aerobic exercises are favourable over strengthening exercises and may be the preferred option for patients with chronic WAD.We found substantial variability in self-reported outcomes within participants, clinicians should be aware of this in the judgement of treatment effectiveness.

Comparative efficacy and acceptability of non-pharmacological interventions in fibromyalgia: Protocol for a network meta-analysis.

INTRODUCTION: Although several non-pharmacological interventions have been tested in the management of Fibromyalgia (FM), there is little consensus regarding the best options for the treatment of this health condition. The purpose of this network meta-analysis (NMA) is to investigate the comparative efficacy and acceptability of non-pharmacological interventions for FM, in order to assist clinical decision making through a ranking of interventions in relation to the most important clinical outcomes in these patients. METHODS AND ANALYSIS: We will perform a systematic search to identify randomised controlled trials of non-pharmacological interventions endorsed in guidelines and systematic reviews. Information sources searched will include major bibliographic databases without language or date restrictions (MEDLINE, Cochrane Library, EMBASE, AMED, PsycINFO and PEDro). Our primary outcomes will be pain intensity, patient-reported quality of life (QoL), and acceptability of treatment will be our secondary outcome. Risk of bias of the included trials will be assessed using the Cochrane risk of bias tool (RoB2). For each pairwise comparison between the different interventions, we will present mean differences (MDs) for pain intensity and QoL outcomes and Relative Risks (RRs) for acceptability, both with respective 95% confidence intervals (CIs). Initially, standard pairwise meta-analyses will be performed using a DerSimonian-Laird random effects model for all comparisons with at least two trials and then we will perform a frequentist NMA using the methodology of multivariate meta-analysis assuming a common heterogeneity parameter, using the mvmeta command and network suite in STATA. In the NMA, two different types of control group, such as placebo/sham and no intervention/waiting list will be combined as one node called "Control". The competing interventions will be ranked using the P-score, which is the frequentist analogue of surface under the cumulative ranking curve (SUCRA) for the outcomes of interest at immediate- (intervention duration of up to 2 weeks), short- (over 2 weeks up to 12 weeks) and long-terms (over 12 weeks). The confidence in the results from NMA will be assessed using the Confidence in Network Meta-analysis (CINeMA) framework. ETHICS AND DISSEMINATION: This work synthesises evidence from previously published studies and does not require ethics review or approval. A manuscript describing the findings will be submitted for publication in a peer-reviewed scientific journal. REGISTRATION: OSF (DOI: 10.17605/OSF.IO/7MS25) and registered in the PROSPERO database (CRD42020216374).

Differences in Structural Brain Characteristics Between Individuals with Chronic Nonspecific Neck Pain and Asymptomatic Controls: A Case-Control Study.

BACKGROUND: Neck pain is a prevalent and costly problem, but its underlying mechanisms are poorly understood. Neuroimaging studies show alterations in brain morphometry in chronic musculoskeletal pain, but reports on neck pain are scarce. OBJECTIVE: This study investigates (1) differences in brain morphometry between individuals with chronic nonspecific neck pain and asymptomatic individuals and (2) associations between brain morphometry and patient-reported outcomes. METHODS: Sixty-three participants (33 pain, 11 female, mean [SD] age 35 [10] years; 30 control, 12 female, age 35 [11] years) underwent magnetic resonance imaging. Brain regions of interest (ROIs) were determined a priori, outcomes included cortical thickness and volume. Between-group differences were determined using cluster-wise correction for multiple comparisons and analyses of pain-related ROIs. RESULTS: Between-group differences in volume were identified in the precentral, frontal, occipital, parietal, temporal, and paracentral cortices. ROI analyses showed that parahippocampal cortical thickness was larger in the neck pain group (p=0.015, 95% CI: -0.27 to -0.03). Moderate to strong associations between volume and thickness of the cingulate cortex, prefrontal cortex, and temporal lobe and neck pain duration, pain intensity, and neck disability were identified (p-values 0.006 to 0.048). CONCLUSION: Alterations in brain morphology that are associated with clinical characteristics inform the mechanisms underlying chronic nonspecific neck pain and may guide the development of more effective treatment approaches.

Genetic basis to structural grey matter associations with chronic 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.

Magnetic Resonance Spectroscopy Assessment of Brain Metabolite Concentrations in Individuals With Chronic Whiplash-associated Disorder: A Cross-sectional Study.

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.

A Pilot Longitudinal Study of 3-Dimensional Head and Neck Kinematics During Functional Tasks in Individuals With Chronic Idiopathic Neck Pain Either Wait-Listed for or Receiving Chiropractic Spinal Manipulative Therapy With Exercise.

OBJECTIVE: The purpose of this study was to determine if there is a relationship between pain and movement kinematics during functional tasks, evaluated over time, in individuals with chronic idiopathic neck pain. METHODS: Ten participants with chronic idiopathic neck pain performed 2 functional tasks (overhead reach to the right and putting on a seatbelt) while evaluated using 8 Oqus 300+ cameras. Kinematic variables included joint angles and range of motion (ROM) (°), head segment relative to neck segment (head-neck [HN]); and head/neck segment relative to upper thoracic segment (head/neck-trunk), velocity (m/s), and time (% of movement phase). Pain was quantified using a 100-mm visual analog scale. Linear mixed effects regression models were used to analyze associations between pain and kinematic variables adjusting for treatment group. RESULTS: For overhead reach, higher pain was associated with less HN peak rotation at baseline (ß = -0.33; 95% CI -0.52 to -0.14, P = .003) and less HN total rotation ROM at 6 months (ß = -0.19; 95% CI -0.38 to -0.003, P = .048). For the seatbelt task, higher pain was associated with less HN peak rotation (ß = -0.52; 95% CI -0.74 to -0.30 to -0.74, P < .001) and less HN total rotation ROM at baseline (ß = -0.32; 95% CI -0.53 to -0.10, P = .006). No other movement variables demonstrated meaningful relationships with pain for the reach or seatbelt tasks. CONCLUSION: Higher pain is associated with less HN peak and total rotation during functional reaching tasks requiring head rotation. Recognizing altered functional kinematics in individuals with chronic neck pain may assist patient management.

Central neurobiological effects of physical exercise in individuals with chronic musculoskeletal pain: a systematic review.

OBJECTIVE: Primary objectives: to investigate the central neurobiological effects (using MRI) of physical exercise in individuals with chronic pain. Secondary objectives: (1) to investigate the associations between central changes and clinical outcomes and (2) to investigate whether different types and dosages of physical exercise exert different central changes. DESIGN: Systematic review searching four electronic databases up to September 2018: AMED, CINAHL, Embase and MEDLINE. Two reviewers independently assessed the methodological quality of included studies using the Cochrane Collaboration's Risk of Bias in Non-Randomised Studies-I tool. A standardised extraction table was used for data extraction, which was performed by two reviewers. INTERVENTIONS: Studies reporting any physical exercise intervention in any chronic musculoskeletal pain condition were included. Eligibility of 4011 records was screened independently by two reviewers, and four studies were included in the review. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome: any brain outcome assessed with any MR technique. SECONDARY OUTCOMES: any self-reported clinical outcomes, and type and dosage of the exercise intervention. RESULTS: All four studies had high risk of bias. There was heterogeneity between the brain areas studied and the types of exercise interventions delivered. All studies reported functional MRI changes in various brain areas following an exercise intervention. Insufficient data were available to conduct a meta-analysis or to answer the secondary aims. CONCLUSIONS: Only a limited number of studies were available and all were at high risk of bias. None of the studies was randomised or included blinded assessment. Exercise may exert effects on brain neurobiology in people with chronic pain. Due to the high risk of bias, future studies should use a randomised study design. Investigation of morphological brain changes could be included. PROSPERO REGISTRATION NUMBER: CRD42018108179.

Systemic inflammatory markers in neck pain: A systematic review with meta-analysis.

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 1ß (SMD: 0.84 [95% CI 0.24, 1.44], p = .01, I2  = 59%) and tumour necrosis factor α (SMD: 0.59 [0.09, 1.09], p = .02, I2  = 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-1ß 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.

Cervical Sensorimotor Control Does Not Change Over Time and Is Not Related to Chronic Idiopathic Neck Pain Characteristics: A 6-Month Longitudinal Observational Study.

BACKGROUND: Cervical sensorimotor control (CSMC) outcomes have been suggested to be important in the assessment of individuals with neck pain, despite the lack of consistent supporting evidence that CSMC skills are related to neck pain. OBJECTIVE: The aim of this study was to investigate whether CSMC changes over time in individuals with chronic idiopathic neck pain and whether neck pain characteristics are associated with CSMC. DESIGN: A longitudinal observational study was performed. METHODS: A total 50 participants with chronic idiopathic neck pain and 50 matched participants who were healthy (controls) completed 7 CSMC tests (including 14 test conditions): joint position error, postural balance, subjective visual vertical, head tilt response, The Fly, smooth pursuit neck torsion, and head steadiness. Neck pain characteristics included pain intensity (visual analog scale), pain duration, and neck disability (Neck Disability Index). Linear mixed models were used to investigate whether any factors were associated with changes in CSMC. RESULTS: Neck pain intensity was associated with 1 of 14 CSMC test conditions (balance with torsion and eyes open), and neck disability was associated with balance with eyes open and high-load head steadiness. Other factors, including sex, age, body mass index, physical activity levels, and neck pain duration, showed no association with CSMC. LIMITATIONS: Although all other tests involved computerized data collection, the joint position error test was administered manually, introducing the risk of researcher bias. CONCLUSIONS: The few associations between test conditions and neck pain characteristics were at best weak; hence, these are likely to be chance findings. These results suggest that CSMC may not be associated with improvement/worsening of chronic idiopathic neck pain, spawning debate on the clinical usefulness of CSMC tests.