A 5-day course of rTMS before pain onset ameliorates future pain and increases sensorimotor peak alpha frequency.

Repetitive transcranial magnetic stimulation (rTMS) has shown promise as an intervention for pain. An unexplored research question is whether the delivery of rTMS prior to pain onset might protect against a future episode of prolonged pain. The present study aimed to determine i) whether 5 consecutive days of rTMS delivered prior to experimentally-induced prolonged jaw pain could reduce future pain intensity and ii) whether any effects of rTMS on pain were mediated by changes in corticomotor excitability (CME) and/or sensorimotor peak alpha frequency (PAF). On each day from Day 0-4, forty healthy individuals received a single session of active (n = 21) or sham (n = 19) rTMS over the left primary motor cortex. PAF and CME were assessed on Day 0 (before rTMS) and Day 4 (after rTMS). Prolonged pain was induced via intramuscular injection of nerve growth factor (NGF) in the right masseter muscle after the final rTMS session. From Days 5-25, participants completed twice-daily electronic dairies including pain on chewing and yawning (primary outcomes), as well as pain during other activities (e.g. talking), functional limitation in jaw function and muscle soreness (secondary outcomes). Compared to sham, individuals who received active rTMS subsequently experienced lower pain on chewing and yawning. Although active rTMS increased PAF, the effects of rTMS on pain were not mediated by changes in PAF or CME. This study is the first to show that rTMS delivered prior to pain onset can protect against future pain and associated functional impairment. Thus, rTMS may hold promise as a prophylactic intervention for persistent pain.

The Influence of Pain Hypersensitivity and Psychological Factors on Pain and Disability in the Transition From Acute to Chronic Low Back Pain: A Longitudinal Exploratory Investigation and Cluster Analysis.

Pain hypersensitivity is present in some people with acute low back pain (LBP) and thought to be involved in the development of chronic LBP. Early evidence suggests that pain hypersensitivity in acute LBP precedes poor long-term outcome. We aimed to examine whether the presence of pain hypersensitivity in acute LBP influenced recovery status at 6 months and differentiated how pain and disability changed over time. Participants with acute nonspecific LBP (<6 weeks after pain onset, N = 118) were included in this longitudinal study. Quantitative sensory testing, including pressure and heat pain thresholds, and conditioned pain modulation and questionnaires were compared at baseline and longitudinally (at 3 and 6 months) between recovered and unrecovered participants. Using k-means clustering, we identified subgroups based on baseline sensory measures alone, and in combination with psychological factors, and compared pain and disability outcomes between subgroups. Sensory measures did not differ at baseline or longitudinally between recovered (N = 50) and unrecovered (N = 68) participants. Subgrouping based on baseline sensory measures alone did not differentiate pain or disability outcomes at any timepoint. Participants with high psychological distress at baseline (N = 19) had greater disability, but not pain, at all timepoints than those with low psychological distress, regardless of the degrees of pain sensitivity. Our findings suggest that pain hypersensitivity in acute LBP does not precede poor recovery at 6 months or differentiate how pain and disability change over time. High psychological distress during acute LBP is associated with unremitting and pronounced disability, while pain severity is unaffected. PERSPECTIVE: Pain hypersensitivity is thought to be involved in the transition to chronic LBP. Contradictory to prevailing hypothesis, our findings suggest pain hypersensitivity alone in acute LBP does not precede poor recovery. High psychological distress in acute LBP has a stronger influence than pain hypersensitivity on long-term disability, but not pain outcomes.

Can non-invasive brain stimulation modulate peak alpha frequency in the human brain? A systematic review and meta-analysis.

Peak alpha frequency (PAF), the dominant oscillatory frequency within the alpha range (8-12 Hz), is associated with cognitive function and several neurological conditions, including chronic pain. Manipulating PAF could offer valuable insight into the relationship between PAF and various functions and conditions, potentially providing new treatment avenues. This systematic review aimed to comprehensively synthesise effects of non-invasive brain stimulation (NIBS) on PAF speed. Relevant studies assessing PAF pre- and post-NIBS in healthy adults were identified through systematic searches of electronic databases (Embase, PubMed, PsychINFO, Scopus, The Cochrane Library) and trial registers. The Cochrane risk-of-bias tool was employed for assessing study quality. Quantitative analysis was conducted through pairwise meta-analysis when possible; otherwise, qualitative synthesis was performed. The review protocol was registered with PROSPERO (CRD42020190512) and the Open Science Framework (https://osf.io/2yaxz/). Eleven NIBS studies were included, all with a low risk-of-bias, comprising seven transcranial alternating current stimulation (tACS), three repetitive transcranial magnetic stimulation (rTMS), and one transcranial direct current stimulation (tDCS) study. Meta-analysis of active tACS conditions (eight conditions from five studies) revealed no significant effects on PAF (mean difference [MD] = -0.12, 95% CI = -0.32 to 0.08, p = 0.24). Qualitative synthesis provided no evidence that tDCS altered PAF and moderate evidence for transient increases in PAF with 10 Hz rTMS. However, it is crucial to note that small sample sizes were used, there was substantial variation in stimulation protocols, and most studies did not specifically target PAF alteration. Further studies are needed to determine NIBS's potential for modulating PAF.

It's OK to Move! Effect of a Brief Video on Community Confidence in Activity Despite Back Pain: A Randomized Trial.

OBJECTIVE: To estimate the difference in confidence to become active despite low back pain in people who were exposed to one of 2 video interventions delivered on social media, compared to no intervention. DESIGN: A proof-of-concept, 3-group randomized controlled trial, in a 1:1:1 ratio. METHODS: Participants aged 18 years and over, with and without low back pain, were recruited via the social media channel Facebook, to view either a humorous video, a neutral video, or to no intervention. The videos were delivered online, explained evidence-based management for low back pain, and were designed to "go viral." The primary outcome was confidence in becoming active despite pain, measured using the Pain Self Efficacy Questionnaire (Item 10) (ranges from 0 [not at all confident] to 6 [completely confident]) immediately after watching the video. We aimed to capture the real-time impact and immediate reactions that contributed to the content's reach. RESULTS: Among 1933 randomized participants (mean [standard deviation] age: 58.9 [14.0] years, 1285 [75%] women), 1232 [70%] had low back pain and 88.8% completed the primary outcome. One thousand two hundred sixty-four participants were randomized to receive a video intervention, and 633 participants did not receive a video. On a 6-point scale, individuals exposed to either video (n = 1088) showed a mean confidence level 0.3 points higher (95% confidence interval: 0.1, 0.6) compared with no video (n = 630). CONCLUSION: Participants who viewed a brief video intervention reported a very small difference in confidence to become active despite low back pain, compared with no intervention. The difference may lack clinical relevance. J Orthop Sports Phys Ther 2024;54(6):1-8. Epub 18 April 2024. doi:10.2519/jospt.2024.12412.

The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation.

Chronic pain is sustained, in part, through the intricate process of central sensitization (CS), marked by maladaptive neuroplasticity and neuronal hyperexcitability within central pain pathways. Accumulating evidence suggests that CS is also driven by neuroinflammation in the peripheral and central nervous system. In any chronic disease, the search for perpetuating factors is crucial in identifying therapeutic targets and developing primary preventive strategies. The brain-derived neurotrophic factor (BDNF) emerges as a critical regulator of synaptic plasticity, serving as both a neurotransmitter and neuromodulator. Mounting evidence supports BDNF's pro-nociceptive role, spanning from its pain-sensitizing capacity across multiple levels of nociceptive pathways to its intricate involvement in CS and neuroinflammation. Moreover, consistently elevated BDNF levels are observed in various chronic pain disorders. To comprehensively understand the profound impact of BDNF in chronic pain, we delve into its key characteristics, focusing on its role in underlying molecular mechanisms contributing to chronic pain. Additionally, we also explore the potential utility of BDNF as an objective biomarker for chronic pain. This discussion encompasses emerging therapeutic approaches aimed at modulating BDNF expression, offering insights into addressing the intricate complexities of chronic pain.

Interhemispheric Inhibition Between Primary Motor Cortices is Not Altered in Individuals With Chronic Lateral Epicondylalgia.

Lateral epicondylalgia (LE), commonly referred to as tennis elbow, is a musculoskeletal condition characterized by pain and sensorimotor dysfunction. In some individuals with chronic unilateral LE, sensorimotor symptoms develop on the unaffected side despite no evidence of tissue damage. Altered interhemispheric inhibition (IHI) is one mechanism that could underpin this phenomenon. The aim of this cross-sectional study was to examine IHI between the primary motor cortices (M1) in individuals with chronic LE and healthy controls. In 20 individuals with chronic LE and 20 healthy participants, transcranial magnetic stimulation was used to assess 1) short and long-latency IHI from the affected (corresponding to the injured side) to the unaffected M1 and 2) corticomotor excitability of the affected and unaffected M1. Sensorimotor function was evaluated bilaterally at the extensor carpi radialis brevis muscle using pressure pain threshold, grip strength, 2-point discrimination, and temporal summation tests. Short- and long-latency IHI from the affected to the unaffected M1 and corticomotor excitability of the affected and unaffected M1 were not altered in individuals with LE compared with healthy participants. No differences in sensorimotor function were observed for the affected or unaffected extensor carpi radialis brevis muscles when individuals with LE were compared with healthy participants. IHI is not altered in individuals with chronic LE. Further studies are required to determine the mechanisms that underpin the development of bilateral sensorimotor symptoms in unilateral LE. PERSPECTIVE: IHI is unaltered from the affected M1 (corresponding to the painful muscle) to unaffected M1 in individuals with LE compared to healthy controls. The absence of bilateral sensorimotor dysfunction and low pain severity in this cohort of individuals with LE may explain this finding.

Combined transcranial magnetic stimulation and electroencephalography reveals alterations in cortical excitability during pain.

Transcranial magnetic stimulation (TMS) has been used to examine inhibitory and facilitatory circuits during experimental pain and in chronic pain populations. However, current applications of TMS to pain have been restricted to measurements of motor evoked potentials (MEPs) from peripheral muscles. Here, TMS was combined with electroencephalography (EEG) to determine whether experimental pain could induce alterations in cortical inhibitory/facilitatory activity observed in TMS-evoked potentials (TEPs). In Experiment 1 (n=29), multiple sustained thermal stimuli were administered to the forearm, with the first, second, and third block of thermal stimuli consisting of warm but non-painful (pre-pain block), painful (pain block) and warm but non-painful (post-pain block) temperatures, respectively. During each stimulus, TMS pulses were delivered while EEG (64 channels) was simultaneously recorded. Verbal pain ratings were collected between TMS pulses. Relative to pre-pain warm stimuli, painful stimuli led to an increase in the amplitude of the frontocentral negative peak ~45 ms post-TMS (N45), with a larger increase associated with higher pain ratings. Experiments 2 and 3 (n=10 in each) showed that the increase in the N45 in response to pain was not due to changes in sensory potentials associated with TMS, or a result of stronger reafferent muscle feedback during pain. This is the first study to use combined TMS-EEG to examine alterations in cortical excitability in response to pain. These results suggest that the N45 TEP peak, which indexes GABAergic neurotransmission, is implicated in pain perception and is a potential marker of individual differences in pain sensitivity.

Sex Differences in the Serum Proteomic Profile During Acute Low Back Pain-A Preliminary Study of the Relationship to Future Low Back Pain.

The molecular processes driving the transition from acute to chronic low back pain (LBP) remain poorly understood and are likely to be sexually dimorphic. This study aimed to explore sex differences in the serum proteomic profile of people experiencing an acute LBP episode and determine if serum protein concentrations were associated with three-month outcome. Serum samples were collected through venepuncture from 30 female and 29 male participants experiencing an acute LBP episode. Serum samples underwent trypsin digestion and fractionation using hydrophobic interaction chromatography and were then analysed using mass-spectrometry. Mass-spectrometry spectra were searched in the Swissprot database for protein identification. Sex differences in protein abundance changes were evident upon inspection of fold changes. Multivariable data analysis identified 21 serum proteins during the acute episode that correctly classified 93% of males and 23 serum proteins that correctly classified 90% of females with ongoing LBP at 3 months. Pathway analysis suggested the differentially expressed proteins during acute LBP were frequently involved in immune, inflammatory, complement, or coagulation responses. This data provides preliminary evidence that biological processes during an acute LBP episode may contribute to the resolution, or persistence, of LBP symptoms at 3 months, however, these processes differ between males and females. PERSPECTIVE: Differential expression of serum proteins was observed between male and female participants during an acute LBP episode. This preliminary work provides a foundation for future research targeting distinct immune system processes in males and females that may interfere with the transition from acute to chronic LBP.

Genome wide association joint analysis reveals 99 risk loci for pain susceptibility and pleiotropic relationships with psychiatric, metabolic, and immunological traits.

Chronic pain is at epidemic proportions in the United States, represents a significant burden on our public health system, and is coincident with a growing opioid crisis. While numerous genome-wide association studies have been reported for specific pain-related traits, many of these studies were underpowered, and the genetic relationship among these traits remains poorly understood. Here, we conducted a joint analysis of genome-wide association study summary statistics from seventeen pain susceptibility traits in the UK Biobank. This analysis revealed 99 genome-wide significant risk loci, 65 of which overlap loci identified in earlier studies. The remaining 34 loci are novel. We applied leave-one-trait-out meta-analyses to evaluate the influence of each trait on the joint analysis, which suggested that loci fall into four categories: loci associated with nearly all pain-related traits; loci primarily associated with a single trait; loci associated with multiple forms of skeletomuscular pain; and loci associated with headache-related pain. Overall, 664 genes were mapped to the 99 loci by genomic proximity, eQTLs, and chromatin interaction and ~15% of these genes showed differential expression in individuals with acute or chronic pain compared to healthy controls. Risk loci were enriched for genes involved in neurological and inflammatory pathways. Genetic correlation and two-sample Mendelian randomization indicated that psychiatric, metabolic, and immunological traits mediate some of these effects.

Knee osteoarthritis patient perspectives of their care in an australian private physiotherapy setting: a qualitative exploratory interview study.

PURPOSE: This study aimed to understand perceptions that knee osteoarthritis patients have regarding their experiences of guideline-based recommendations within their care received from physiotherapists in private practice. METHODS: A qualitative semi-structured interview study nested within a larger trial auditing care provided by physiotherapists. Recruited adults ≥ 45 years with knee osteoarthritis across nine primary care physiotherapy practices. Interview questions were anchored around the core elements recommended in guidelines for the management of knee osteoarthritis and patient perceptions of these were analysed using both content and thematic qualitative analysis approaches. Patient satisfaction with care received was asked at the time of interview. RESULTS: Twenty-six patients volunteered for the study (mean 60 years, 58% female). Analysis identified that physiotherapists focused on treating symptoms through quadriceps strengthening exercises, which patients found to be effective, though focussed less on other aspects of evidenced-based care. Patient's perceived treatment to be effective in relieving pain and enabling them to stay active and they appreciated the positive role that their physiotherapist provided in alleviating their concerns. Overall, patients were satisfied with their physiotherapy care but would have liked more specific osteoarthritis education and longer-term management. CONCLUSION: The description of the physiotherapy-related care received by people with knee osteoarthritis aligns with guideline recommendations, though mainly for strength-related exercise prescription. Despite some perceived shortfalls in care, patients do appear to be satisfied. However, improvements in patient outcomes may be possible if more elements of guideline-base care are regularly provided, including enhancing osteoarthritis education and fostering behaviour change. TRIAL REGISTRATION: ACTRN12620000188932.

Systemic pro- and anti-inflammatory profiles in acute non-specific low back pain: An exploratory longitudinal study of the relationship to six-month outcome.

OBJECTIVES: Pro-inflammatory molecules are thought to underpin the development of chronic low back pain (LBP). Although research has begun to explore the association between pro-inflammatory molecules in acute LBP and long-term outcome, no study has explored the role of anti-inflammatory molecules. We aimed to explore whether levels of systemic pro- and anti-inflammatory molecules 1) changed over a period of six months from the onset of acute LBP; 2) differed between people who were recovered (N = 11) and unrecovered (N = 24) from their episode of LBP at six months; 3) baseline psychological factors were related to inflammatory molecule serum concentrations at baseline, three and six months. METHODS: We retrospectively included participants with acute LBP included from a larger prospective trial and examined blood samples for the measurement of pro- and anti-inflammatory molecules and measures of pain, disability, and psychological factors at baseline, three and six months. RESULTS: The serum concentrations of pro- and anti-inflammatory molecules did not differ over time when compared between participants who recovered and those who did not recover at six-month follow-up. At three months, the unrecovered group had higher interleukin (IL)-8 and IL-10 serum concentrations than the recovered group. Baseline psychological factors were not related to inflammatory molecules at any time point. DISCUSSION: This exploratory study showed that levels of systemic inflammatory molecules did not change over the course of LBP, irrespective of whether people were recovered or unrecovered at six months. There was no relationship between acute-stage psychological factors and systemic inflammatory molecules. Further investigation is needed to elucidate the contribution of pro- and anti-inflammatory molecules to long-term LBP outcome.

Alterations in cortical excitability during pain: A combined TMS-EEG Study.

Transcranial magnetic stimulation (TMS) has been used to examine inhibitory and facilitatory circuits during experimental pain and in chronic pain populations. However, current applications of TMS to pain have been restricted to measurements of motor evoked potentials (MEPs) from peripheral muscles. Here, TMS was combined with electroencephalography (EEG) to determine whether experimental pain could induce alterations in cortical inhibitory/facilitatory activity observed in TMS-evoked potentials (TEPs). In Experiment 1 (n = 29), multiple sustained thermal stimuli were administered to the forearm, with the first, second and third block of thermal stimuli consisting of warm but non-painful (pre-pain block), painful (pain block) and warm but non-painful (post-pain block) temperatures respectively. During each stimulus, TMS pulses were delivered while EEG (64 channels) was simultaneously recorded. Verbal pain ratings were collected between TMS pulses. Relative to pre-pain warm stimuli, painful stimuli led to an increase in the amplitude of the frontocentral negative peak ~45ms post-TMS (N45), with a larger increase associated with higher pain ratings. Experiments 2 and 3 (n = 10 in each) showed that the increase in the N45 in response to pain was not due to changes in sensory potentials associated with TMS, or a result of stronger reafferent muscle feedback during pain. This is the first study to use combined TMS-EEG to examine alterations in cortical excitability in response to pain. These results suggest that the N45 TEP peak, which indexes GABAergic neurotransmission, is implicated in pain perception and is a potential marker of individual differences in pain sensitivity.

Comparative effectiveness and safety of analgesic medicines for adults with acute non-specific low back pain: systematic review and network meta-analysis.

OBJECTIVE: To evaluate the comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, PubMed, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and World Health Organization's International Clinical Trials Registry Platform from database inception to 20 February 2022. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials of analgesic medicines (eg, non-steroidal anti-inflammatory drugs, paracetamol, opioids, anti-convulsant drugs, skeletal muscle relaxants, or corticosteroids) compared with another analgesic medicine, placebo, or no treatment. Adults (≥18 years) who reported acute non-specific low back pain (for less than six weeks). DATA EXTRACTION AND SYNTHESIS: Primary outcomes were low back pain intensity (0-100 scale) at end of treatment and safety (number of participants who reported any adverse event during treatment). Secondary outcomes were low back specific function, serious adverse events, and discontinuation from treatment. Two reviewers independently identified studies, extracted data, and assessed risk of bias. A random effects network meta-analysis was done and confidence was evaluated by the Confidence in Network Meta-Analysis method. RESULTS: 98 randomised controlled trials (15 134 participants, 49% women) included 69 different medicines or combinations. Low or very low confidence was noted in evidence for reduced pain intensity after treatment with tolperisone (mean difference -26.1 (95% confidence intervals -34.0 to -18.2)), aceclofenac plus tizanidine (-26.1 (-38.5 to -13.6)), pregabalin (-24.7 (-34.6 to -14.7)), and 14 other medicines compared with placebo. Low or very low confidence was noted for no difference between the effects of several of these medicines. Increased adverse events had moderate to very low confidence with tramadol (risk ratio 2.6 (95% confidence interval 1.5 to 4.5)), paracetamol plus sustained release tramadol (2.4 (1.5 to 3.8)), baclofen (2.3 (1.5 to 3.4)), and paracetamol plus tramadol (2.1 (1.3 to 3.4)) compared with placebo. These medicines could increase the risk of adverse events compared with other medicines with moderate to low confidence. Moderate to low confidence was also noted for secondary outcomes and secondary analysis of medicine classes. CONCLUSIONS: The comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain are uncertain. Until higher quality randomised controlled trials of head-to-head comparisons are published, clinicians and patients are recommended to take a cautious approach to manage acute non-specific low back pain with analgesic medicines. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019145257.

Relative and absolute reliability of somatosensory evoked potentials in response to non-noxious electrical stimulation of the paraspinal muscles in healthy participants at an interval of 3-months.

BACKGROUND: Somatosensory evoked potentials (SEPs) are used extensively to quantify cortical activity in response to noxious and/or non-noxious sensory stimuli. However, data demonstrating the reliability of SEP measures in response to non-noxious stimulation over time are scarce. AIM: We investigated the relative and absolute reliability, and the smallest detectable change at 95% confidence (SDC95) for SEPs evoked by non-noxious electrical stimulation of the paraspinal muscles in thirty-nine healthy participants at a 3-month interval. METHODS: SEPs were evoked at an intensity three-times that of each participant's perceptual threshold and recorded from a single electrode placed over the primary somatosensory cortex (S1). RESULTS: Our analyses reveal that i) latency, as a measure of activity onset, has poor relative reliability but good absolute reliability; ii) area, as a measure of cortical activity, has good relative and absolute reliability (except for the N150 component) and iii) perceptual threshold and stimulation intensity was not reliable over time. CONCLUSION: These findings suggest that the area of the N80 and P260 SEP components, and the area of the N80-N150-P260 SEP complex, can be utilised in future studies as reliable markers of cortical activity.

Cortical function and sensorimotor plasticity are prognostic factors associated with future low back pain after an acute episode: the Understanding persistent Pain Where it ResiDes prospective cohort study.

ABSTRACT: Predicting the development of chronic low back pain (LBP) at the time of an acute episode remains challenging. The Understanding persistent Pain Where it ResiDes study aimed to identify neurobiological and psychological risk factors for chronic LBP. Individuals with acute LBP (N = 120) participated in a prospective cohort study with 6-month follow-up. Candidate predictors were selected from the neurobiological (eg, sensorimotor cortical excitability assessed by sensory and motor-evoked potentials and brain-derived neurotrophic factor genotype), psychological (eg, depression and anxiety), symptom-related (eg, LBP history), and demographic domains. Analyses involved multivariable linear regression models with pain intensity or disability degree as continuous variables. Secondary analyses involved a multivariable logistic model with the presence of LBP at 6 months (thresholding pain intensity and disability degree) as a dichotomous variable. Lower sensory cortex and corticomotor excitability, higher baseline pain intensity, higher depression, stress, and pain catastrophizing were the strongest predictors ( R2 = 0.47) of pain intensity at 6 months. Older age and higher pain catastrophizing were the strongest predictors ( R2 = 0.30) of disability at 6 months. When the LBP outcome was dichotomised, sensory cortex and corticomotor excitability, brain-derived neurotrophic factor genotype, depression and anxiety, LBP history and baseline pain intensity, discriminated between those who did and did not report LBP at 6 months (C-statistic 0.91). This study identifies novel risk factors for the development of future LBP. Neurobiological risk factors, when added to a multivariable linear regression model, explained a further 15% of the variance in the 6-month pain intensity.

The reliability of two prospective cortical biomarkers for pain: EEG peak alpha frequency and TMS corticomotor excitability.

BACKGROUND: Many pain biomarkers fail to move from discovery to clinical application, attributed to poor reliability and an inability to accurately classify at-risk individuals. Preliminary evidence has shown that high pain sensitivity is associated with slow peak alpha frequency (PAF), and depression of corticomotor excitability (CME), potentially due to impairments in ascending sensory and descending motor pathway signalling respectively NEW METHOD: The present study evaluated the reliability of PAF and CME responses during sustained pain. Specifically, we determined whether, over several days of pain, a) PAF remains stable and b) individuals show two stable and distinct CME responses: facilitation and depression. Participants were given an injection of nerve growth factor (NGF) into the right masseter muscle on Day 0 and Day 2, inducing sustained pain. Electroencephalography (EEG) to assess PAF and transcranial magnetic stimulation (TMS) to assess CME were recorded on Day 0, Day 2 and Day 5. RESULTS: Using a weighted peak estimate, PAF reliability (n = 75) was in the excellent range even without standard pre-processing and ∼2 min recording length. Using a single peak estimate, PAF reliability was in the moderate-good range. For CME (n = 74), 80% of participants showed facilitation or depression of CME beyond an optimal cut-off point, with the stability of these changes in the good range. COMPARISON WITH EXISTING METHODS: No study has assessed the reliability of PAF or feasibility of classifying individuals as facilitators/depressors, in response to sustained pain. PAF was reliable even in the presence of pain. The use of a weighted peak estimate for PAF is recommended, as excellent test-retest reliability can be obtained even when using minimal pre-processing and ∼2 min recording. We also showed that 80% of individuals exhibit either facilitation or depression of CME, with these changes being stable across sessions. CONCLUSIONS: Our study provides support for the reliability of PAF and CME as prospective cortical biomarkers. As such, our paper adds important methodological advances to the rapidly growing field of pain biomarkers.

Human assumed central sensitization in people with acute non-specific low back pain: A cross-sectional study of the association with brain-derived neurotrophic factor, clinical, psychological and demographic factors.

BACKGROUND: Early evidence suggests human assumed central sensitization (HACS) is present in some people with acute low back pain (LBP). Factors influencing individual variation in HACS during acute LBP have not been fully explored. We aimed to examine the evidence for HACS in acute LBP and the contribution of brain-derived neurotrophic factor (BDNF), clinical, psychological and demographic factors to HACS. METHODS: Participants with acute LBP (<6 weeks after pain onset, N = 118) and pain-free controls (N = 57) from a longitudinal trial were included. Quantitative sensory testing including pressure and heat pain thresholds and conditioned pain modulation, BDNF serum concentration and genotype and questionnaires were assessed. RESULTS: There were no signs of HACS during acute LBP at group level when compared with controls. Sensory measures did not differ when compared between controls and LBP participants with different BDNF genotypes. Two LBP subgroups with distinct sensory profiles were identified. Although one subgroup (N = 60) demonstrated features of HACS including pressure/heat pain hypersensitivity at a remote site and deficient conditioned pain modulation, pain severity and disability did not differ between the two subgroups. Variation in sensory measures (~33%) was partially explained by BDNF genotype, sex, age and psychological factors. CONCLUSIONS: This study confirms that HACS is present in some people with acute LBP, but this was not associated with pain or disability. Further, no relationship was observed between BDNF and HACS in acute LBP. More research is needed to understand factors contributing to individual variation in sensory measures in LBP. SIGNIFICANCE: Human assumed central sensitization (HACS) is present in acute low back pain (LBP) but factors contributing to individual variation are not fully explored. This study investigated the relationship between factors such as brain derived neurotrophic factor (BDNF) and HACS in acute LBP. Our findings indicate that HACS was present in specific LBP subgroups but BDNF was unrelated to HACS. Combinations of BDNF genotype, demographic and psychological factors explained a small proportion of the variation in sensory measures during acute LBP.

The effect of exercise engagement on low back disability at 12-months is mediated by pain and catastrophizing in a community sample of people with chronic low back pain.

Despite being a first-line treatment recommendation, there is uncertainly for how exercise helps people with chronic low back pain. We designed this study to examine how exercise might help people with chronic low back pain by following a large community sample for 1-year. Qualitative questionnaires and self-report measures were collected every 3-months for 1-year in 400 people with chronic low back pain. People were not provided any specific treatment advice as part of this study but were allowed to engage with any normal physical activity, treatment, or medication as part of their normal life. Exercise engagement was defined from inspection of participant qualitative responses, according to minimum acceptable levels of exercise that elicit symptom reduction. Multiple mediation analysis was performed to examine the effect of exercise engagement on disability through the proposed mediators (pain, fear, catastrophizing, depression, anxiety, self-efficacy). The significant effect of exercise engagement on reductions in disability at 6- and 12-months was explained through pain and catastrophizing. People with chronic low back pain who reported worsening of symptoms over the year had similar reporting of exercise throughout the 12-months to people who had improvements in disability. Exercise can reduce disability through the effect on pain and catastrophizing, but how this effect occurs (i.e., an active or passive component of exercise) is unclear.

A snapshot of primary care physiotherapy management of knee osteoarthritis in an Australian setting: does it align with evidence-based guidelines?

BACKGROUND: Systematic implementation of evidence-based, clinical practice guidelines for management of knee osteoarthritis (OA) in primary care physiotherapy in Australia is embryonic. Clinical practice guidelines have been implemented in the public healthcare sector at a State-level for physiotherapists in the form of multidisciplinary programs, but the reach of physiotherapy-led OA management programs is grossly inadequate in the private sector. OBJECTIVE: To provide a snapshot of the management of people with knee OA in private physiotherapy practice in an Australian setting. Primarily the aim was to determine the alignment between the treatment provided and guideline-based management. Secondary aims included the capture of both patient-reported improvement after 3-months and patient satisfaction with treatment. Whether patient-reported outcome measures (PROMS) were routinely used was also ascertained. METHODS: A prospective, observational study enrolling adults >=45 years with knee OA across nine primary care physiotherapy practices. Knee injury OA Outcome Score (KOOS) and Routine Assessment Patient Index 3 (RAPID3) were collected (baseline; 3 months) by researchers along with satisfaction with treatment. Treatment details and use of PROMS were obtained from physiotherapy record audit and patient interview. The treatment provided was compared to the minimum core elements of management stipulated in OA management guidelines. RESULTS: Twenty-six adults (58% female, mean age 60 (9) years, 54% overweight or obese) participated. 100% were prescribed ≥1 appropriate exercise(s); 42% received OA education; 12% received weight management advice. Mean improvement (95%CI) in KOOS Pain was 9.8 (3.4 to 16.1) and RAPID3 was -3.4 (-5.5 to -1.3). Satisfaction with treatment was high (8.3/10). No PROMs were used for assessment or monitoring. CONCLUSION: Primary care physiotherapy treatment of knee OA did not meet minimum criteria per clinical practice guidelines. However, participant improvement at three months reached minimally important change thresholds for patient-reported measures and satisfaction was high. The data provide useful insights about areas that are deficient, thus, should inform future implementation strategies designed to improve care delivery and the uptake of routine measurement of patient-reported outcomes.

It's safe to move! A protocol for a randomised controlled trial investigating the effect of a video designed to increase people's confidence becoming more active despite back pain.

INTRODUCTION: Social media provide promising contemporary platforms for sharing public health information with a broad audience. Before implementation, testing social media campaigns that are intended to engage audiences and initiate behaviour change is necessary. This trial aims to investigate the effectiveness of a public health campaign to increase people's confidence in becoming more active despite low back pain in comparison with no intervention. METHODS AND ANALYSIS: This is an online randomised controlled trial with two intervention groups and one control group in a 1:1:1 allocation. People over 18 years of age and fluent in English will be recruited via social media advertising. We developed a social media-based public health campaign to support recommendations for managing low back pain. The interventions are two videos. Participants in the control group will be asked questions about low back pain but will not view either video intervention. The primary outcome will be item 10 of the Pain Self-Efficacy Questionnaire, which asks participants to rate how confident they would feel to gradually become more active despite pain ranging from 0 (not at all confident) to 6 (completely confident). This outcome will be measured immediately in all participant groups. We will compare group mean of the three arms of the trial using univariate analyses of variance. ETHICS AND DISSEMINATION: This trial has been prospectively registered with the Australian New Zealand Clinical Trials Registry. We obtained ethical approval from our institutions Human Research Ethics Committee before data collection. We will publish the results in a peer-reviewed medical journal and on institution websites. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12622000466741).