The effects of aerobic exercise on neuroimmune responses in animals with traumatic peripheral nerve injury: a systematic review with meta-analyses.

BACKGROUND: Increasing pre-clinical evidence suggests that aerobic exercise positively modulates neuroimmune responses following traumatic nerve injury. However, meta-analyses on neuroimmune outcomes are currently still lacking. This study aimed to synthesize the pre-clinical literature on the effects of aerobic exercise on neuroimmune responses following peripheral nerve injury. METHODS: MEDLINE (via Pubmed), EMBASE and Web of Science were searched. Controlled experimental studies on the effect of aerobic exercise on neuroimmune responses in animals with a traumatically induced peripheral neuropathy were considered. Study selection, risk of bias assessment and data extraction were performed independently by two reviewers. Results were analyzed using random effects models and reported as standardized mean differences. Outcome measures were reported per anatomical location and per class of neuro-immune substance. RESULTS: The literature search resulted in 14,590 records. Forty studies were included, reporting 139 comparisons of neuroimmune responses at various anatomical locations. All studies had an unclear risk of bias. Compared to non-exercised animals, meta-analyses showed the following main differences in exercised animals: (1) in the affected nerve, tumor necrosis factor-α (TNF-α) levels were lower (p = 0.003), while insulin-like growth factor-1 (IGF-1) (p < 0.001) and Growth Associated Protein 43 (GAP43) (p = 0.01) levels were higher; (2) At the dorsal root ganglia, brain-derived neurotrophic factor (BDNF)/BDNF mRNA levels (p = 0.004) and nerve growth factor (NGF)/NGF mRNA (p < 0.05) levels were lower; (3) in the spinal cord, BDNF levels (p = 0.006) were lower; at the dorsal horn, microglia (p < 0.001) and astrocyte (p = 0.005) marker levels were lower; at the ventral horn, astrocyte marker levels (p < 0.001) were higher, and several outcomes related to synaptic stripping were favorably altered; (4) brainstem 5-HT2A receptor levels were higher (p = 0.001); (5) in muscles, BDNF levels (p < 0.001) were higher and TNF-α levels lower (p < 0.05); (6) no significant differences were found for systemic neuroimmune responses in blood or serum. CONCLUSION: This review revealed widespread positive modulatory effects of aerobic exercise on neuroimmune responses following traumatic peripheral nerve injury. These changes are in line with a beneficial influence on pro-inflammatory processes and increased anti-inflammatory responses. Given the small sample sizes and the unclear risk of bias of the studies, results should be interpreted with caution.

Preferred Self-Administered Questionnaires to Assess Resilience, Optimism, Pain Acceptance, and Social Support in People with Pain: A Modified Delphi Study.

OBJECTIVES: The plethora of self-administered questionnaires to assess positive psychosocial factors complicates questionnaire selection. This study aimed to identify and reach consensus on the most suitable self-administered questionnaires to assess resilience, optimism, pain acceptance and social support in people with pain. DESIGN: A three-round modified Delphi study. PARTICIPANTS: Forty international experts. METHODS: In Round 1, the experts suggested questionnaires deemed appropriate to assess resilience, optimism, pain acceptance and/or social support. In Round 2, experts indicated whether they considered the suggested questionnaires to be suitable (Yes/No/Don't know) to assess these psychosocial factors, taking into consideration content, feasibility, personal experience and the measurement properties which we provided for each questionnaire. Questionnaires that were considered suitable by the majority of experts (≥60%) were retained for Round 3. In Round 3, the suitability of each questionnaire was rated on a 0-10 Likert scale. Consensus was reached if ≥75% of experts rated the questionnaire ≥7. RESULTS: From the 67 questionnaires suggested in Round 1, one questionnaire could be recommended per domain. For resilience: Pain Resilience Scale; for optimism: Revised Version of the Life Orientation Test; for pain acceptance: 8-item and Revised Versions of the Chronic Pain Acceptance Questionnaire; for social support: Emotional Support Item Bank of the PROMIS tool. Consensus for these questionnaires was also reached in a sensitivity analysis which excluded the ratings of experts involved in the development, translation and/or validation of relevant questionnaires. CONCLUSION: We advocate the use of these recommended questionnaires so data can be compared and pooled more easily.

An individualized decision between physical therapy or surgery for patients with degenerative meniscal tears cannot be based on continuous treatment selection markers: a marker-by-treatment analysis of the ESCAPE study.

PURPOSE: Marker-by-treatment analyses are promising new methods in internal medicine, but have not yet been implemented in orthopaedics. With this analysis, specific cut-off points may be obtained, that can potentially identify whether meniscal surgery or physical therapy is the superior intervention for an individual patient. This study aimed to introduce a novel approach in orthopaedic research to identify relevant treatment selection markers that affect treatment outcome following meniscal surgery or physical therapy in patients with degenerative meniscal tears. METHODS: Data were analysed from the ESCAPE trial, which assessed the treatment of patients over 45 years old with a degenerative meniscal tear. The treatment outcome of interest was a clinically relevant improvement on the International Knee Documentation Committee Subjective Knee Form at 3, 12, and 24 months follow-up. Logistic regression models were developed to predict the outcome using baseline characteristics (markers), the treatment (meniscal surgery or physical therapy), and a marker-by-treatment interaction term. Interactions with p < 0.10 were considered as potential treatment selection markers and used these to develop predictiveness curves which provide thresholds to identify marker-based differences in clinical outcomes between the two treatments. RESULTS: Potential treatment selection markers included general physical health, pain during activities, knee function, BMI, and age. While some marker-based thresholds could be identified at 3, 12, and 24 months follow-up, none of the baseline characteristics were consistent markers at all three follow-up times. CONCLUSION: This novel in-depth analysis did not result in clear clinical subgroups of patients who are substantially more likely to benefit from either surgery or physical therapy. However, this study may serve as an exemplar for other orthopaedic trials to investigate the heterogeneity in treatment effect. It will help clinicians to quantify the additional benefit of one treatment over another at an individual level, based on the patient's baseline characteristics. LEVEL OF EVIDENCE: II.

Identifying the Most Important Confounders When Assessing the Association Between Low-Grade Systemic Inflammation and Musculoskeletal Pain: A Modified Delphi Study.

OBJECTIVE: The association between low-grade systemic inflammation and musculoskeletal pain may be influenced by multiple factors. However, little is known about the relative importance of these factors, and few studies account for them. This Delphi study aimed to reach consensus on the most important confounders which influence the association between low-grade systemic inflammation and musculoskeletal pain. METHODS: The panel consisted of 48 experts. In Round 1, the experts proposed what they believed were important confounders. In Round 2, the experts indicated for each confounder whether they believed it was important (yes/no). At least 50% of experts had to indicate the confounder was important to be considered in the final round. In Round 3, the experts rated the importance of each confounder on a 7-point Likert scale. Consensus was reached if ≥75% of the experts considered the factor either extremely or moderately important. RESULTS: In Round 1, 120 confounders were proposed, which were synthesized into 38 distinct factors. In Round 2, 33 confounders met the criterion to be considered important. In Round 3, consensus was reached for 14 confounders: acute illness/trauma, immune disease, medication use, endocrine, nutritional, or metabolic disease, other musculoskeletal conditions, age, handling of blood samples, sex, cancer, body composition, pregnancy, cardiovascular disease, physical activity, and pain characteristics. CONCLUSIONS: These findings provide insight in the complexity of the association between low-grade systemic inflammation and musculoskeletal pain. Some factors currently listed as confounders may be re-classified as moderators or mediators as insights progress.

High concurrent validity between digital and analogue algometers to measure pressure pain thresholds in healthy participants and people with migraine: a cross-sectional study.

BACKGROUND: Pressure pain thresholds (PPTs) are commonly assessed to quantify mechanical sensitivity in various conditions, including migraine. Digital and analogue algometers are used, but the concurrent validity between these algometers is unknown. Therefore, we assessed the concurrent validity between a digital and analogue algometer to determine PPTs in healthy participants and people with migraine. METHODS: Twenty-six healthy participants and twenty-nine people with migraine participated in the study. PPTs were measured interictally and bilaterally at the cephalic region (temporal muscle, C1 paraspinal muscles, and trapezius muscle) and extra-cephalic region (extensor carpi radialis muscle and tibialis anterior muscle). PPTs were first determined with a digital algometer, followed by an analogue algometer. Intraclass correlation coefficients (ICC3.1) and limits of agreement were calculated to quantify concurrent validity. RESULTS: The concurrent validity between algometers in both groups was moderate to excellent (ICC3.1 ranged from 0.82 to 0.99, with 95%CI: 0.65 to 0.99). Although PPTs measured with the analogue algometer were higher at most locations in both groups (p < 0.05), the mean differences between both devices were less than 18.3 kPa. The variation in methods, such as a hand-held switch (digital algometer) versus verbal commands (analogue algometer) to indicate when the threshold was reached, may explain these differences in scores. The limits of agreement varied per location and between healthy participants and people with migraine. CONCLUSION: The concurrent validity between the digital and analogue algometer is excellent in healthy participants and moderate in people with migraine. Both types of algometer are well-suited for research and clinical practice but are not exchangeable within a study or patient follow-up.

How do people in China think about causes of their back pain? A predominantly qualitative cross-sectional survey.

BACKGROUND: Low back pain (LBP) is the second highest cause of health burden in China. Delayed recovery, poor clinical outcomes and persistence of LBP are associated with negative pain beliefs about LBP. Chinese philosophies are nested into the daily life of people in China, which is likely to influence pain beliefs. However, there is lack of knowledge about people's discourses regarding their LBP in China. The primary aim of this study was to explore the discourses underlying the beliefs of people in China about what causes their persistent or recurrent LBP. The secondary aim was to investigate the sources of these pain beliefs. METHODS: People (n = 152) from South Central, East and North Mainland China with LBP completed an online survey about what they believed caused their persistent or recurrent LBP and where these understandings came from. Potential causes of persistent or recurrent LBP were explored qualitatively using discourse analysis. The sources of these discourses were assessed by descriptive statistics with conventional content analysis. RESULTS: Five discourses were identified to underpin participants' beliefs about what caused their persistent or recurrent LBP, namely: (1) biomedical problems (66.4%), (2) unbalanced lifestyle (48.7%), (3) menstruation and 'kidney' status (9.2%), (4) the 'Five Elements' imbalance (7.9%), and (5) energy status (5.9%). Most participants responded that their pain beliefs were based on information derived from healthcare professionals (59.2%), followed by the internet (24.3%) and family (23.0%). CONCLUSIONS: People from moderately and well-developed parts of Mainland China think predominantly in line with a Western biomedical viewpoint about their LBP. Traditional Chinese medicine related pain beliefs mainly to the concept of 'balance' were evident on contemporary Chinese society's understandings of LBP. These cultural beliefs could be relevant to consider in LBP management and involve healthcare professionals, family and patient in this process.

Fluctuations in local and widespread mechanical sensitivity throughout the migraine cycle: a prospective longitudinal study.

BACKGROUND: People with migraine have localised (i.e., cephalic) mechanical sensitivity. There is uncertainty regarding widespread (i.e., extra-cephalic) mechanical sensitivity and variations in mechanical sensitivity throughout the migraine cycle. Therefore, this study aimed (1) to comprehensively assess mechanical sensitivity in both cephalic and extra-cephalic regions during the preictal, ictal, postictal and interictal phases; and (2) to compare these findings with mechanical sensitivity at corresponding time-points and locations in healthy participants. METHODS: According to sample size calculations, 19 people with migraine and 19 matched healthy volunteers participated in a prospective longitudinal study. Pressure pain thresholds were evaluated in three cephalic regions (temporalis, upper trapezius and C1 paraspinal muscles) and two extra-cephalic regions (extensor carpi radialis and tibialis anterior muscle) with a digital algometer during the four phases of the migraine cycle in people with migraine and at corresponding intervals and locations in healthy participants. Linear mixed model analyses with a random intercept were used. RESULTS: People with migraine had increased mechanical sensitivity in cephalic and extra-cephalic regions in all phases of the migraine cycle compared to healthy participants. Furthermore, this mechanical sensitivity was more severe in the preictal, ictal and postictal phase compared to the interictal phase in cephalic and extra-cephalic regions. CONCLUSION: People with migraine have localised as well as widespread mechanical sensitivity compared to healthy participants. This sensitivity is even more pronounced immediately before, during and after a migraine attack.

The impact of being overweight or obese on 12 month clinical recovery in patients following lumbar microdiscectomy for radiculopathy.

BACKGROUND CONTEXT: The proportion of patients who undergo lumbar microdiscectomy due to lumbar radiculopathy who are also overweight or obese is high. However, whether high body mass index (BMI) affects clinical outcomes is not well-studied. PURPOSE: To investigate the difference in the clinical course between normal weight, overweight, and obese patients with radiculopathy who underwent lumbar microdiscectomy followed by physical therapy and to evaluate whether high BMI is associated with poor recovery. STUDY DESIGN/SETTING: A prospective cohort study with a 12-month follow-up was conducted in a multidisciplinary clinic. PATIENT SAMPLE: We included 583 patients (median [IQR] age: 45 [35-52] years; 41% female) with clinical signs and symptoms of lumbar radiculopathy, consistent with magnetic resonance imaging findings, who underwent microdiscectomy followed by postoperative physical therapy. OUTCOME MEASURES: Outcomes were leg pain and back pain intensity measured with a visual analogue scale, disability measured with the Roland Morris Disability Questionnaire at 3 and 12-month follow-ups, and complications. METHODS: Patients were classified as being normal weight (46.9%), overweight (38.4%), or obese (14.7%). A linear mixed-effects model was used to assess the difference in the clinical course of pain and disability between the three BMI categories. The association between BMI and outcomes was evaluated using univariable and multivariable logistic regression analyses. RESULTS: All three patient groups experienced a significant improvement in leg pain, back pain, and disability over 3 and 12-month follow-up. Patients who were overweight, obese, or normal weight experienced comparable leg pain (p=.14) and disability (p=.06) over the clinical course (p=.14); however, obese patients experienced higher back pain (MD=-6.81 [95%CI: -13.50 to -0.14]; p=.03). The difference in back pain scores was not clinically relevant. CONCLUSIONS: In the first year following lumbar microdiscectomy, patients demonstrated clinical improvements and complications that were unrelated to their preoperative BMI.

Assessing the Influence of Nonischemic A-Fiber Conduction Blockade on Offset Analgesia: An Experimental Study.

Offset analgesia (OA) is believed to reflect the efficiency of the endogenous pain modulatory system. However, the underlying mechanisms are still being debated. Previous research suggested both, central and peripheral mechanisms, with the latter involving the influence of specific A-delta-fibers. Therefore, this study aimed to investigate the influence of a nonischemic A-fiber conduction blockade on the OA response in healthy participants. A total of 52 participants were recruited for an A-fiber conduction blockade via compression of the superficial radial nerve. To monitor fiber-specific peripheral nerve conduction capacity, quantitative sensory testing was performed continuously. Before, during, and after the A-fiber block, an individualized OA paradigm was applied to the dorsum of both hands (blocked and control sides were randomized). The pain intensity of each heat stimulus was evaluated by an electronic visual analog scale. A successful A-fiber conduction blockade was achieved in thirty participants. OA has been verified within time (before, during, and after blockade) and condition (blocked and control side) (P < .01, d > .5). Repeated measurements analysis of variance showed no significant interaction effects between OA within condition and time (P = .24, η²p = .05). Hence, no significant effect of A-fiber blockade was detected on OA during noxious heat stimulation. The results suggest that peripheral A-fiber afferents may play a minor role in OA compared with alternative central mechanisms or other fibers. However, further studies are needed to substantiate a central rather than peripheral influence on OA. PERSPECTIVE: This article presents the observation of OA before, during, and after a successful A-fiber conduction blockade in healthy volunteers. A better understanding of the mechanisms of OA and endogenous pain modulation, in general, may help to explain the underlying aspects of pain disorders.

Systemic Inflammation, Sleep, and Psychological Factors Determine Recovery Trajectories for People With Neck Pain: An Exploratory Study.

We conducted an explorative prospective cohort study with 6 months follow-up to 1) identify different pain and disability trajectories following an episode of acute neck pain, and 2) assess whether neuroimmune/endocrine, psychological, behavioral, nociceptive processing, clinical outcome, demographic and management-related factors differ between these trajectories. Fifty people with acute neck pain (ie, within 2 weeks of onset) were included. At baseline, and at 2, 4, 6, 12, and 26 weeks follow-up, various neuroimmune/endocrine (eg, inflammatory cytokines and endocrine factors), psychological (eg, stress symptoms), behavioral (eg, sleep disturbances), nociceptive processing (eg, condition pain modulation), clinical outcome (eg, trauma), demographic factors (eg, age), and management-related factors (eg, treatment received) were assessed. Latent class models were performed to identify outcome trajectories for neck pain and disability. Linear mixed models or the Pearson chi-square test were used to evaluate differences in these factors between the trajectories at baseline and at each follow-up assessment and over the entire 6 months period. For pain, 3 trajectories were identified. The majority of patients were assigned to the "Moderate pain - Favourable recovery" trajectory (n = 25; 50%) with smaller proportions assigned to the "Severe pain - Favourable recovery" (n = 16; 32%) and the "Severe pain - Unfavourable recovery" (n = 9; 18%) trajectories. For disability, 2 trajectories were identified: "Mild disability - Favourable recovery" (n = 43; 82%) and "Severe disability - Unfavourable recovery" (n = 7; 18%). Ongoing systemic inflammation (increased high-sensitive C-reactive protein), sleep disturbances, and elevated psychological factors (such as depression, stress and anxiety symptoms) were mainly present in the unfavorable outcome trajectories compared to the favorable outcome trajectories. PERSPECTIVE: Using exploratory analyses, different recovery trajectories for acute neck pain were identified based on disability and pain intensity. These trajectories were influenced by systemic inflammation, sleep disturbances, and psychological factors.

(Cost-)effectiveness of personalised multimodal physiotherapy compared to surgery in patients with cervical radiculopathy: A systematic review.

RATIONALE: Cervical radiculopathy is initially typically managed conservatively. Surgery is indicated when conservative management fails or with severe/progressive neurological signs. Personalised multimodal physiotherapy could be a promising conservative strategy. However, aggregated evidence on the (cost-)effectiveness of personalised multimodal physiotherapy compared to surgery with/without post-operative physiotherapy is lacking. AIM/OBJECTIVES: To systematically summarise the literature on the (cost-)effectiveness of personalised multimodal physiotherapy compared to surgery with or without post-operative physiotherapy in patients with cervical radiculopathy. METHODS: PubMed, Embase, CINAHL, PsycINFO and Web of Science were searched from inception to 1st of March 2023. Primary outcomes were effectiveness regarding costs, arm pain intensity and disability. Neck pain intensity, perceived recovery, quality of life, neurological symptoms, range-of-motion, return-to-work, medication use, (re)surgeries and adverse events were considered secondary outcomes. Randomised clinical trials comparing personalised multimodal physiotherapy versus surgical approaches with/without post-operative physiotherapy were included. Two independent reviewers performed study selection, data-extraction, and risk of bias assessment using the Cochrane RoB 2 and Consolidated Health Economic Evaluation Reporting Standards statement. Certainty of the evidence was determined using Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: From 2109 records, eight papers from two original trials, with 117 participants in total were included. Low certainty evidence showed there were no significant differences on arm pain intensity and disability, except for the subscale 'heavy work' related disability (12 months) and disability at 5-8 years. Cost-effectiveness was not assessed. There was low certainty evidence that physiotherapy improved significantly less on neck pain intensity, sensory loss and perceived recovery compared to surgery with/without physiotherapy. Low certainty evidence showed there were no significant differences on numbness, range of motion, medication use, and quality of life. No adverse events were reported. CONCLUSION: Considering the clinical importance of accurate management recommendations and the current low level of certainty, high-quality cost-effectiveness studies are needed.

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.

Translating the new International IFOMPT Cervical Framework into a framework flowchart for clinical practice and education.

BACKGROUND: In 2020, a revised version of the International IFOMPT Cervical Framework was published. This framework provides both physical therapists and educators the necessary information to guide the assessment of the cervical spine region for potential vascular pathologies of the neck in advance of planned Orthopaedic Manual Therapy (OMT) interventions. OBJECTIVE: The objective was to develop a framework flowchart which is useful in clinical practice and education to assist physical therapists to improve the safety of OMT, and apply this in a case report. METHODS: The framework was developed in co-creation with manual therapy experts, researchers, educators in manual therapy, patients, medical specialists and the Manual Therapy Association in The Netherlands and Belgium. Manual therapists and patients tested the framework for intelligibility and usefulness. RESULTS: A framework flowchart is developed and presented, that is easy to use in both clinical practice and education. It is a visual representation of the sequence of steps and decisions needed during the process. A case description of a patient with neck pain and headache is added to illustrate the clinical usefulness of the framework flowchart. CONCLUSION: The framework flowchart helps physical therapists in their clinical reasoning to provide safe OMT interventions.

Lifestyle factors and psychological factors are associated with central pain processing in service members with persistent low-back pain: A cross-sectional exploratory study.

Persistent low-back pain (LBP) is highly prevalent in the military. Altered central pain processing is one of the mechanisms found to underlie persistent LBP. Our aim was to explore which factors are associated with altered pain processing in Dutch service members with persistent LBP. This knowledge may guide clinicians in what factors to address in the treatment of dysfunctional pain processing in service members with persistent LBP. Twenty-one service members with persistent LBP (mean age 34.0 years, 18 males) were included in this cross-sectional exploratory study. Participants completed questionnaires regarding lifestyle and psychological factors. Altered central pain processing was measured by temporal summation of pain to examine the function of the pain facilitatory system and by conditioned pain modulation to examine the pain inhibitory function. Univariable and multivariable linear regression analyses were performed. A higher local temporal summation of pain was associated with a longer sitting time, a higher level of physical activity and a higher level of pain catastrophizing. A higher local conditioned pain modulation was associated with a higher level of pain catastrophizing, anxiety and depression symptoms, and with a lower sleep quality. A higher remote conditioned pain modulation effect was associated with a higher level of physical activity, a higher body mass index and a shorter sitting time. This study succeeded in identifying lifestyle and psychological factors associated with altered pain processing in service members with persistent LBP. Prospective studies are needed to examine causality in these relationships.

Novice assessors demonstrate good intra-rater agreement and reliability when determining pressure pain thresholds; a cross-sectional study.

Background: Experienced assessors show good intra-rater reproducibility (within-session and between-session agreement and reliability) when using an algometer to determine pressure pain thresholds (PPT). However, it is unknown whether novice assessors perform equally well. This study aimed to determine within and between-session agreement and reliability of PPT measurements performed by novice assessors and explored whether these parameters differed per assessor and algometer type. Methods: Ten novice assessors measured PPTs over four test locations (tibialis anterior muscle, rectus femoris muscle, extensor carpi radialis brevis muscle and paraspinal muscles C5-C6) in 178 healthy participants, using either a Somedic Type II digital algometer (10 raters; 88 participants) or a Wagner Force Ten FDX 25 digital algometer (nine raters; 90 participants). Prior to the experiment, the novice assessors practiced PPTs for 3 h per algometer. Each assessor measured a different subsample of ~9 participants. For both the individual assessor and for all assessors combined (i.e., the group representing novice assessors), the standard error of measurement (SEM) and coefficient of variation (CV) were calculated to reflect within and between-session agreement. Reliability was assessed using intraclass correlation coefficients (ICC1,1). Results: Within-session agreement expressed as SEM ranged from 42 to 74 kPa, depending on the test location and device. Between-session agreement, expressed as SEM, ranged from 36 to 76 kPa and the CV ranged from 9-16% per body location. Individual assessors differed from the mean group results, ranging from -55 to +32 kPa or from -9.5 to +6.6 percentage points. Reliability was good to excellent (ICC1,1: 0.87 to 0.95). Results were similar for both types of algometers. Conclusions: Following 3 h of algometer practice, there were slight differences between assessors, but reproducibility in determining PPTs was overall good.

Is there a geographic and gender divide in Europe regarding the biopsychosocial approach to pain research? An evaluation of the 12th EFIC congress.

OBJECTIVES: All pain research combined advances the different domains of the biopsychosocial model and its interactions. However, there may be discrepancies between individual countries in their biomedical, psychological or social focus to pain research. As a proxy for this possible discrepancy, we analysed the biopsychosocial orientation of presentations at a recent major international pain conference. METHODS: The primary aim was to investigate whether there are geographical differences across Europe regarding the biopsychosocial orientation of workshop presentations at the 12th EFIC congress. The secondary aim was to investigate whether there were differences between female and male presenters regarding the biopsychosocial focus of their presentations. All available workshop abstracts were blinded and categorised by two independent reviewers as biomedical, psychosocial, biopsychosocial, or not applicable. Psychosocial and biopsychosocial were merged to non-biomedical. RESULTS: Of the 140 available abstracts, 126 abstracts could be categorised (biomedical: 51 %; non-biomedical: 49 %). Three clusters of countries emerged: (1) countries with a clear majority (≥80 %) of non-biomedical presentations (The Netherlands and Belgium); (2) countries with a balance between biomedical and non-biomedical presentations (United Kingdom, Denmark, Norway, Sweden and Finland); and (3) countries with a clear majority (71-100 %) of biomedical presentations (Italy, Germany, Switzerland and France). Overall, women delivered more presentations than men (70 vs. 56 presentations), and delivered proportionally more non-biomedical presentations (57 %) whereas men delivered proportionally more biomedical presentations (61 %). CONCLUSIONS: Analysis of the 12th EFIC congress revealed geographical and gender differences in biopsychosocial orientation. Whether this reflects established differences in pain research requires further investigation.

Immediate systemic neuroimmune responses following spinal mobilisation and manipulation in people with non-specific neck pain: a randomised placebo-controlled trial.

Spinal mobilisation/manipulation is a common intervention for spinal pain, yet the working mechanisms are largely unknown. A randomised placebo-controlled trial was conducted to (1) compare the immediate neuroimmune responses following spinal mobilisation/manipulation and placebo spinal mobilisation/manipulation; (2) compare the immediate neuroimmune responses of those with a good outcome with those of a poor outcome following spinal mobilisation/manipulation; and (3) explore the association between neuroimmune responses and pain reduction. One hundred patients were randomly allocated to spinal mobilisation/manipulation or a placebo mobilisation/manipulation. Primary outcomes were whole blood in-vitro evoked released concentrations of IL-1ß and TNF-α measured 10 min and 2 h after the intervention. Immediate effects were studied because successful mobilisation/manipulation is often associated with immediate pain reduction, and immediate neuroimmune responses are less affected by potential confounders than long-term responses. Secondary outcomes included multiple systemic inflammatory marker concentrations, phenotypic analysis of white blood cells and clinical outcomes. Outcomes were compared between the experimental and placebo group, and between people with a good and poor outcome in the experimental group. Estimates of intervention effects were based on intention-to-treat analyses, by using linear mixed-effect models. Although there was a substantial difference in pain reduction between groups (mean (SD) difference visual analogue scale: 30 (21) mm at 10 min and 32 (21) mm at 2 h (p < 0.001) in favour of mobilisation/manipulation, there were no differences in primary outcomes between groups or between people with a good and poor outcome (p ≥ 0.10). In conclusion, possible neuroimmune responses following spinal mobilisations/manipulation cannot be identified at a systemic level. Future research may focus on longer treatment duration and more localised neuroimmune responses.

Variability in recovery following microdiscectomy and postoperative physiotherapy for lumbar radiculopathy: A latent class trajectory analysis.

OBJECTIVES: The clinical course of lumbar radiculopathy following microdiscectomy and post-operative physiotherapy varies substantially. No prior studies assessed this variability by deriving outcome trajectories. The primary aims of this study were to evaluate the variability in long-term recovery after lumbar microdiscectomy followed by post-operative physiotherapy and to identify outcome trajectories. The secondary aim was to assess whether demographic, clinical characteristics and patient-reported outcome measures routinely collected at baseline could predict poor outcome trajectories. METHODS: We conducted a prospective cohort study with a 24-month follow-up. We included 479 patients with clinical signs and symptoms of lumbar radiculopathy confirmed by Magnetic Resonance Imaging findings, who underwent microdiscectomy and post-operative physiotherapy. Outcomes were leg pain and back pain measured with Visual Analogue Scales, and disability measured with the Roland-Morris Disability Questionnaire. Descriptive statistics were performed to present the average and the individual clinical course. A latent class trajectory analysis was conducted to identify leg pain, back pain, and disability outcome trajectories. The best number of clusters was determined using the Bayesian Information Criterion, Akaike's information criteria, entropy, and overall interpretability. Prediction models for poor outcome trajectories were assessed using multivariable logistic regression analyses. RESULTS: Several outcome trajectories were identified. Most patients were assigned to the 'large improvement' trajectory (leg pain: 79.3%; back pain: 70.2%; disability: 59.5% of patients). Smaller proportions of patients were assigned to the 'moderate improvement' trajectory (leg pain: 7.9%; back pain: 10.6%; disability: 20.7% of patients), the 'minimal improvement' trajectory (leg pain: 4.9%, back pain: 6.7%, disability: 16.3% of patients) and the 'relapse' trajectory (leg pain: 7.9%; back pain: 12.5%; disability: 3.5%). Approximately one-third of patients (32.6%) belonged to one or more than one poor outcome trajectory. Patients with previous treatment (prior back surgery, injection therapy, and medication use) and those who had higher baseline pain and disability scores were more likely to belong to the poor outcome trajectories in comparison to the large improvement trajectories in back pain, leg pain and disability, and the moderate improvement trajectory in disability. The explained variance (Nagelkerke R2) of the prediction models ranged from 0.06 to 0.13 and the discriminative ability (Area Under the Curve) from 0.66 to 0.73. CONCLUSION: The clinical course of lumbar radiculopathy varied following microdiscectomy and post-operative physiotherapy, and several outcome trajectories could be identified. Although most patients were allocated to favorable trajectories, one in three patients was assigned to one or more poor outcome trajectories following microdiscectomy and post-operative physiotherapy for lumbar radiculopathy. Routinely gathered data were unable to predict the poor outcome trajectories accurately. Prior to surgery, clinicians should discuss the high variability and the distinctive subgroups that are present in the clinical course with their patients.

Exploratory Study of Associations and Agreement between Prognostic Patient-Registered Factors, Physiotherapists' Intuitive Synthesis, and Patient-Reported Factors in Whiplash-Associated Disorders.

BACKGROUND: A large proportion of people who sustain a whiplash injury will have persistent pain, disability, and participation problems. Several prognostic factors for functional recovery have been reported in the literature but these factors are often evaluated based on differing implementations in clinical practice. Additionally, physiotherapists also rely on their clinical intuition to estimate the functional prognosis of their patients, but this is seldom measured in experimental research. Furthermore, no study to date has explored the associations between clinical intuition, clinically estimated factors, and objectively measured factors for functional recovery of patients with Whiplash-Associated Disorders (WAD). AIM: The aim of this exploratory study is to evaluate associations between prognostic factors for functional recovery, based on routinely collected data in a specialized primary care physiotherapy practice in a consecutive sample of patients (n = 523) with WAD. METHODS: Three sources of prognostic factors were selected: (1) physiotherapists' synthesis of clinical intuition in terms of high-risk, inconclusive risk, or low-risk for functional recovery, (2) patient-registered factors from history taking, and (3) patient-reported prognostic factors derived from questionnaires. Prognostic factors were selected based on the literature, recommendations in Dutch clinical practice guidelines, and consensus between experts. Spearman's rank correlation coefficients were calculated to explore the associations between sources of prognostic factors, using a cutoff ≥0.25 for acceptable association. RESULTS: Associations between physiotherapists' intuitive synthesis and patient-registered variables were substantial (rs = 0.86), between patient-registered variables and patient-reported variables fair (ranging from 0.30 to 0.41) to substantial (ranging from 0.69 to 0.73), and between physiotherapists intuitive synthesis and patient-reported variables fair (ranging from 0.30 to 0.37). CONCLUSION: When estimating prognosis for functional recovery using clinical reasoning, physiotherapists should integrate patients' registered experience of their course of recovery, as well as the timeline after an accident, with their own synthesis of clinical intuition regarding prognostic factors in patients with WAD.

The potential protective effects of pre-injury exercise on neuroimmune responses following experimentally-induced traumatic neuropathy: a systematic review with meta-analysis.

Pre-clinical evidence shows that neuropathy is associated with complex neuroimmune responses, which in turn are associated with increased intensity and persistence of neuropathic pain. Routine exercise has the potential to mitigate complications of future nerve damage and persistence of pain through neuroimmune regulation. This systematic review aimed to explore the effect of pre-injury exercise on neuroimmune responses, and other physiological and behavioural reactions following peripheral neuropathy in animals. Three electronic databases were searched from inception to July 2022. All controlled animal studies assessing the influence of an active exercise program prior to experimentally-induced traumatic peripheral neuropathy compared to a non-exercise control group on neuroimmune, physiological and behavioural outcomes were selected. The search identified 17,431 records. After screening, 11 articles were included. Meta-analyses showed that pre-injury exercise significantly reduced levels of IL-1ß (SMD: -1.06, 95% CI: -1.99 to -0.13, n=40), but not iNOS (SMD: -0.71 95% CI: -1.66 to 0.25, n=82). From 72 comparisons of different neuroimmune outcomes at different anatomical locations, vote counting revealed reductions in 23 pro-inflammatory and increases in 6 anti-inflammatory neuroimmune outcomes. For physiological outcomes, meta-analyses revealed that pre-injury exercise improved one out of six nerve morphometric related outcomes (G-ratio; SMD: 1.95, 95%CI: 0.77 to 3.12, n=20) and one out of two muscle morphometric outcomes (muscle fibre cross-sectional area; SMD: 0.91, 95%CI: 0.27 to 1.54, n=48). For behavioural outcomes, mechanical allodynia was significantly less in the pre-injury exercise group (SMD -1.24, 95%CI: -1.87 to -0.61) whereas no overall effect was seen for sciatic function index. Post hoc subgroup analysis suggests that timing of outcome measurement may influence the effect of pre-injury exercise on mechanical allodynia. Risk of bias was unclear in most studies, as the design and conduct of the included experiments were poorly reported. Preventative exercise may have potential neuroprotective and immunoregulatory effects limiting the sequalae of nerve injury, but more research in this field is urgently needed.