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It remains unclear to what extent Transcranial Magnetic Stimulation-evoked potentials (TEPs) reflect sensory (auditory and somatosensory) potentials as opposed to cortical excitability. The present study aimed to determine; a) the extent to which sensory potentials contaminate TEPs using a spatially-matched sham condition, and b) whether sensory potentials reflect auditory or somatosensory potentials alone, or a combination of the two.Twenty healthy participants received active or sham stimulation, with the latter consisting a sham coil click combined with scalp electrical stimulation. Two additional conditions i) electrical stimulation and ii) auditory stimulation alone, were included in a subset of 13 participants.Signals from active and sham stimulation were correlated in spatial and temporal domains 55 ms post-stimulation. Relative to auditory or electrical stimulation alone, sham stimulation resulted in a) larger potentials, b) stronger correlations with active stimulation and c) a signal that was not a linear sum of electrical and auditory stimulation alone.Sensory potentials can confound interpretations of TEPs at timepoints 55 ms post-stimulation. Furthermore, TEP contamination cannot be explained by auditory or somatosensory potentials alone, but instead reflects a non-linear interaction between both.Future studies may benefit from controlling for sensory contamination using spatially-matched sham conditions, and which consist of combined auditory and somatosensory stimulation.

Bilateral deficits in sensorimotor function have been observed in unilateral musculoskeletal pain conditions. Altered interhemispheric inhibition (IHI) between primary sensory cortices (S1s) is one mechanism that could explain this phenomenon. However, IHI between S1s in response to acute muscle pain, and the relationship between IHI and pressure pain sensitivity in the unaffected limb have not been examined. In 21 healthy individuals, IHI was assessed using somatosensory evoked potentials in response to paired median nerve electrical stimulation at: 1) baseline; 2) immediately following pain resolution; and 3) at 30-minutes follow-up. Acute muscle pain was induced by injection of hypertonic saline into the right abductor pollicis brevis (APB) muscle. Pressure pain thresholds were assessed at the right and left APB muscles before and 30-minutes after pain resolution. Compared to baseline, IHI from the affected to unaffected S1 was unaltered in response to acute muscle pain immediately following pain resolution, or at 30-minutes follow-up. Pressure pain thresholds were reduced over the right (P = .001) and left (P = .001) APB muscles at 30-minutes follow-up. These findings suggest IHI between S1s is unaffected by acute, short-lasting muscle pain, despite the development of increased sensitivity to pressure in the unaffected APB muscle. PERSPECTIVE: IHI from the affected S1 (contralateral to the side of pain) to unaffected S1 is unaltered following the resolution of acute muscle pain. This finding suggests that IHI between S1s may not be relevant in the development of bilateral sensorimotor symptoms in unilateral pain conditions.

Transcranial magnetic stimulation (TMS) has been used to examine the 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 over the forearm, with the first, second and third block of stimuli consisting of warm but non-painful (pre-pain block), painful heat (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.

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.

This observational study evaluated people's attitudes towards educational statements and tested whether this predicted intention to self-manage low back pain (LBP).People with or without LBP who were over 18-years of age and fluent in written English were recruited. Participants completed an online survey asking demographic questions and questions on the presence or absence of LBP, its duration and intensity. We assessed attitude toward educational statements and conducted linear regression analyses to investigate the relationship between attitude toward each statement and intention to self-manage.We recruited 656 participants, n=345(53.6%), with LBP of varying duration. On average, participants had a positive attitude toward all statements except one; participants with chronic LBP had a negative attitude toward a statement relating to the cause of LBP. The effect of attitude on intention to self-manage was dependent on whether someone had LBP and for how long. For example, increased intention to self-manage was predicted by a positive attitude toward educational statements related to staying active [β= 0.22 (CI 0.11 to 0.33] in participants without pain, statements about reassurance [β=0.33 (CI 0.16 to 0.49] for participants with acute or subacute LBP, and statements about the severity of back pain [β= 0.25 (CI 0.18 to 0.33] for participants with chronic LBP.We noted differences in attitude toward educational messages and individuals' intention to self-manage LBP depending on pain duration. Self-management could be encouraged with specific reassurance in people with acute or subacute LBP and education about severity in people with chronic LBP.

Objective: To determine the acceptability and feasibility of acupuncture for the treatment of endometriosis-related chronic pelvic pain. Design: A prospective, randomized controlled feasibility study. Setting: Outpatient setting in Sydney, Australia. Subjects: Participants who were aged 18-45 years, had a confirmed laparoscopic diagnosis of endometriosis in the past 5 years, and had regular menstrual periods and mean pelvic pain scores ≥4/10. Interventions: Sixteen acupuncture treatments delivered by registered acupuncturists using a standardized point protocol over 8 weeks, twice per week plus usual care compared with usual care alone. Outcome measures: Primary outcome measures were feasibility, safety, and acceptability of the acupuncture intervention. Secondary outcomes were changes in self-reported pelvic pain scores, changes in quality of life as measured by the Endometriosis Health Profile (EHP-30), changes in descending pain modulation, and changes in systemic inflammation (plasma interleukin [IL-6] concentrations). Results: Twenty-nine participants were eligible to participate, with 19 participants completing the trial. There was unequal withdrawals between groups; the acupuncture group had a withdrawal rate of 14% compared with 53% in usual care. Adverse events were uncommon (6.7%) and generally mild. A 1.9 point decrease in median nonmenstrual pain scores and a 2.0 decrease in median menstrual pain scores between baseline and end of trial were observed in the acupuncture group only. Improvements in all domains of the EHP-30 were seen in the acupuncture group, with no changes seen in usual care. There was no difference between baseline and end of treatment in IL-6 concentrations for either group. Conclusions: Acupuncture was an acceptable, well-tolerated treatment and it may reduce pelvic pain and improve quality of life; however, usual care was not an acceptable control group. Trial Registration: anzctr.org.au: ACTRN12617000053325. Prospectively registered January 11, 2017.

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.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.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.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.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.

Nociceptive stimulation is predicted to uniformly inhibit motoneurone pools of painful muscles and those producing painful movements. Although reduced motoneurone discharge rate during pain provides some evidence, recent data show evidence of increased excitability of some motoneurones. These observations suggest non-uniform effects of nociception on motoneurone excitability. More direct measures are required, but this is difficult to assess as few measures enable in vivo evaluation of motoneurone excitability in humans. We investigated changes in motoneurone excitability during experimental pain using two methods in separate experiments: (i) estimation of the time-course of motoneurone afterhyperpolarization (AHP) from interval death rate analysis of interspike intervals of single motor unit discharge; and (ii) probability of early motoneurone discharge to a descending volley excited using transcranial magnetic stimulation (TMS). Tibialis anterior motor units were recorded with fine-wire electrodes before, during and after painful infusion of 5% hypertonic saline into the muscle. Activation of 17 units (16 participants) could be used for AHP analysis. Data show shortened (n = 11) and lengthened (n = 6) AHP time-course. Increased (n = 6) and decreased (n = 6) probability of early motoneurone discharge were observed in the TMS experiment. These convergent observations suggest non-uniform effects of nociceptive stimulation on motoneurone pools. This does not support the hypothesis that nociceptive input induces uniform inhibition of painful muscle. Instead, interpretation of results implies redistribution of activity between motor units, with possible benefit for unloading painful tissues. This finding supports an interpretation that differs from the generally accepted view in pain physiology regarding adaptation to motor function in pain.

IntroductionSocial 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 analysisThis 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 disseminationThis 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 numberAustralian New Zealand Clinical Trials Registry (ACTRN12622000466741).

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.We investigated the relative and absolute reliability, and the smallest detectable change at 95% confidence (SDCSEPs 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).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 NThese findings suggest that the area of the N

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.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.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.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.

Summary Objective Guidelines recommend exercise as a core treatment for knee osteoarthritis. However, it is unclear how exercise affects measures of pain processing and motor function. The aim was to evaluate the effect of exercise on measures of pain processing and motor function in people with knee osteoarthritis. Methods We searched five electronic databases (MEDLINE, EMBASE, CINAHL, SCOPUS and Cochrane Central Register of Controlled Trials) for studies on knee osteoarthritis, of any design, evaluating pain processing and motor function before and after exercise. Data were pooled with random-effects meta-analysis. Study quality was assessed using the Downs and Black and quality of evidence was assessed using the GRADE. Results Eighteen studies were eligible and 16 were included. Following acute exercise, pressure pain threshold increased local to the study limb (standardised mean difference [95% confidence interval (CI)] 0.26, [0.02, 0.51], n = 159 from 5 studies), but there was no statistically significant change remote from the study limb (0.09, [-0.11, 0.29], n = 90 from 4 studies). Following an exercise program (range 5–12 weeks) there were no statistically significant changes in pressure pain threshold (local 0.23, [-0.01, 0.47], n = 218 from 8 studies; remote 0.33 [-0.13, 0.79], n = 76 from 4 studies), temporal pain summation (0.38 [-0.08, 0.85], n = 122 from 3 studies) or voluntary quadriceps muscle activation (4.23% [-1.84 to 10.30], n = 139 from 4 studies). Conclusion Very-low quality evidence suggests that pressure pain threshold increases following acute exercise. Very-low quality evidence suggests that pressure pain threshold, temporal pain summation or voluntary quadriceps activation do not change statistically significantly following exercise programs.

Pain alters motor function. This is supported by studies showing reduced corticomotor excitability in response to experimental pain lastinglt;90 minutes. Whether similar reductions in corticomotor excitability are present with pain of longer durations or whether alterations in corticomotor excitability are associated with pain severity is unknown. Here we evaluated the evidence for altered corticomotor excitability in response to experimental pain of differing durations in healthy individuals. Databases were systematically searched for eligible studies. Measures of corticomotor excitability and pain were extracted. Meta-analyses were performed to examine: (1) group-level effect of pain on corticomotor excitability, and (2) individual-level associations between corticomotor excitability and pain severity. 49 studies were included. Corticomotor excitability was reduced when pain lasted milliseconds-seconds (hedges g's = -1.26 to -1.55) and minutes-hours (g's = -0.55 to -0.9). When pain lasted minutes-hours, a greater reduction in corticomotor excitability was associated with lower pain severity (g = -0.24). For pain lasting days-weeks, there were no group level effects (g = -0.18 to 0.27). However, a greater reduction in corticomotor excitability was associated with higher pain severity (g = 0.229). In otherwise healthy individuals, suppression of corticomotor excitability may be a beneficial short-term strategy with long-term consequences. PERSPECTIVE: This systematic review synthesised the evidence for altered corticomotor excitability in response to experimentally induced pain. Reduced corticomotor excitability was associated with lower acute pain severity but higher sustained pain severity, suggesting suppression of corticomotor excitability may be a beneficial short-term adaptation with long-term consequences.

BackgroundDespite chronic low back pain (LBP) being considered a biopsychosocial condition for diagnosis and management, few studies have investigated neurophysiological or neurobiological risk factors thought to underpin the transition from acute to chronic LBP. The aim of this cohort profile is to describe the methodology, compare baseline characteristics between acute LBP participants and pain-free controls, and compare LBP participants with or without completed follow-up.Methods120 individuals experiencing acute LBP and 57 pain-free controls were recruited to participate in the Understanding Persistent Pain Where it Resides (UPWaRD) study. Screening was conducted via email and phone. Neurobiological, psychological, and sociodemographic data were collected at baseline, three- and six-months. LBP status was assessed using the numerical rating scale and Roland-Morris disability questionnaire at three and six-month follow-up.Results95 participants (79%) provided outcome data at three-month follow-up and 96 participants (80%) at six-months. Participants who did not complete follow-up at three- and six-months within the UPWaRD LBP cohort had higher psychological distress, higher pain interference, higher levels of moderate physical activity, and reported occupational difficulties due to pain (P = P = < 0.01).ConclusionsThis cohort profile reports baseline characteristics of the UPWaRD LBP and pain-free control cohort.

BackgroundTranscranial magnetic stimulation (TMS) evoked potentials (TEPs) can be used to index cortical excitability. However, it remains unclear to what extent TEPs reflect somatosensory and auditory-evoked potentials which arise from the scalp sensation and click of the TMS coil, as opposed to transcranial stimulation of cortical circuits.ObjectivesThe present study had two aims; a) to determine the extent to which sensory potentials contaminate TEPs using a spatially matched sham condition, and b) to determine whether sensory potentials reflect auditory or somatosensory potentials alone, or a combination of the two.MethodsTwenty healthy participants received active or sham stimulation, with the latter consisting of the click of a sham coil combined with scalp electrical stimulation. Earplugs/headphones were used to suppress the TMS click noise. Two additional control conditions i) electrical stimulation alone and ii) auditory stimulation alone were included in a subset of 13 participants.ResultsSignals from active and sham stimulation were correlated in spatial and temporal domains, especially >70ms post-stimulation. Relative to auditory or electrical stimulation alone, combined (sham) stimulation resulted in a) larger evoked responses b) stronger correlations with active stimulation and c) a signal that could not be explained by the linear sum of electrical and auditory stimulation alone.ConclusionsSensory potentials can confound data interpretations of TEPs at timepoints >70ms post-TMS, while earlier timepoints appear reflective of cortical excitability. Furthermore, contamination of TEPs cannot be explained by auditory or somatosensory potentials alone, but instead reflects a non-linear interaction between both sources. Future studies may benefit from controlling for sensory contamination using sham conditions that are spatially matched to active TMS, and which consist of combined auditory and somatosensory stimulation.

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.

Introduction Clinician time and resources may be underutilised if the treatment they offer does not match patient expectations and attitudes. We developed a questionnaire (AxEL-Q) to guide clinicians toward elements of first-line care that are pertinent to their patients with low back pain. Methods We used guidance from the COSMIN consortium to develop the questionnaire and evaluated it in a sample of people with low back pain of any duration. Participants were recruited from the community, were over 18 years and fluent in English. Statements that represented first-line care were identified. Semantic scales were used to measure attitude towards these statements. These items were combined to develop the questionnaire draft. Construct validity was evaluated with exploratory factor analysis and hypotheses testing, comparing to the Back Beliefs Questionnaire and modified Pain Self-Efficacy Questionnaire. Reliability was evaluated and floor and ceiling effects calculated. Results We recruited 345 participants, and had complete data for analysis for 313 participants. The questionnaire draft was reduced to a 3-Factor questionnaire through exploratory factor analysis. Factor 1 comprised 9 items and evaluated Attitude toward staying active, Factor 2 comprised 4 items and evaluated Attitude toward low back pain being rarely caused by a serious health problem, Factor 3 comprised 4 items and evaluated Attitude toward not needing to know the cause of back pain to manage it effectively. There was a strong inverse association between each factor and the Back Beliefs Questionnaire and a moderate positive association with the modified Pain Self-Efficacy Questionnaire. Each independent factor demonstrated acceptable internal consistency; Cronbach α Factor 1 = 0.92, Factor 2 = 0.91, Factor 3 = 0.90 and adequate interclass correlation coefficients; Factor 1 = 0.71, Factor 2 = 0.73, Factor 3 = 0.79. Conclusion This study demonstrates acceptable construct validity and reliability of the AxEL-Q, providing clinicians with an insight into the likelihood of patients following first-line care at the outset.

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 (UPWaRD) 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 six-month follow-up. Candidate predictors were selected from the neurobiological (e.g. sensorimotor cortical excitability assessed by sensory and motor evoked potentials, Brain Derived Neurotrophic Factor genotype), psychological (e.g. depression and anxiety), symptom-related (e.g. 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 presence of low back pain at six 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 six months. Older age and higher pain catastrophizing were the strongest predictors (R2=0.30) of disability at six months. When LBP outcome was dichotomised, sensory cortex and corticomotor excitability, BDNF genotype, depression and anxiety, LBP history and baseline pain intensity, accurately discriminated those who did and did not report LBP at six months (c-statistic 0.91). This study identifies novel risk factors for future LBP after an acute episode that can predict an individual’s pain intensity and level of disability at six-month follow-up, and accurately discriminate between those who will and will not report LBP at six months.

Objective To investigate the efficacy, acceptability, and safety of muscle relaxants for low back pain. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and WHO ICTRP from inception to 23 February 2021. Eligibility criteria for study selection Randomised controlled trials of muscle relaxants compared with placebo, usual care, waiting list, or no treatment in adults (≥18 years) reporting non-specific low back pain. Data extraction and synthesis Two reviewers independently identified studies, extracted data, and assessed the risk of bias and certainty of the evidence using the Cochrane risk-of-bias tool and Grading of Recommendations, Assessment, Development and Evaluations, respectively. Random effects meta-analytical models through restricted maximum likelihood estimation were used to estimate pooled effects and corresponding 95% confidence intervals. Outcomes included pain intensity (measured on a 0-100 point scale), disability (0-100 point scale), acceptability (discontinuation of the drug for any reason during treatment), and safety (adverse events, serious adverse events, and number of participants who withdrew from the trial because of an adverse event). Results 49 trials were included in the review, of which 31, sampling 6505 participants, were quantitatively analysed. For acute low back pain, very low certainty evidence showed that at two weeks or less non-benzodiazepine antispasmodics were associated with a reduction in pain intensity compared with control (mean difference −7.7, 95% confidence interval−12.1 to−3.3) but not a reduction in disability (−3.3, −7.3 to 0.7). Low and very low certainty evidence showed that non-benzodiazepine antispasmodics might increase the risk of an adverse event (relative risk 1.6, 1.2 to 2.0) and might have little to no effect on acceptability (0.8, 0.6 to 1.1) compared with control for acute low back pain, respectively. The number of trials investigating other muscle relaxants and different durations of low back pain were small and the certainty of evidence was reduced because most trials were at high risk of bias. Conclusions Considerable uncertainty exists about the clinical efficacy and safety of muscle relaxants. Very low and low certainty evidence shows that non-benzodiazepine antispasmodics might provide small but not clinically important reductions in pain intensity at or before two weeks and might increase the risk of an adverse event in acute low back pain, respectively. Large, high quality, placebo controlled trials are urgently needed to resolve uncertainty. Systematic review registration PROSPERO CRD42019126820 and Open Science Framework https://osf.io/mu2f5/ .

Determining the mechanistic causes of complex biopsychosocial health conditions such as low back pain (LBP) is challenging, and research is scarce. Cross-sectional studies demonstrate altered excitability and organization of the somatosensory and motor cortex in people with acute and chronic LBP, however, no study has explored these mechanisms longitudinally or attempted to draw causal inferences. Using sensory evoked potential area measurements and transcranial magnetic stimulation derived map volume we analyzed somatosensory and motor cortex excitability in 120 adults experiencing acute LBP. Following multivariable regression modelling with adjustment for confounding, we identified lower primary (OR = 2.08, 95% CI = 1.22–3.57) and secondary (OR = 2.56, 95% CI = 1.37–4.76) somatosensory cortex excitability significantly increased the odds of developing chronic pain at 6-month follow-up. Corticomotor excitability in the acute stage of LBP was associated with higher pain intensity at 6-month follow-up (B = -0.15, 95% CI: -0.28 to -0.02) but this association did not remain after confounder adjustment. These data provide evidence that low somatosensory cortex excitability in the acute stage of LBP is a cause of chronic pain. Perspective This prospective longitudinal cohort study design identified low sensorimotor cortex excitability during the acute stage of LBP in people who developed chronic pain. Interventions that target this proposed mechanism may be relevant to the prevention of chronic pain.

The etiologic role of work-related psychological stress in the development of musculoskeletal pain disorders (MDs) has been systematically investigated. Less clear, however, is the role of perceived stress and life stressors. This review aimed to assess the evidence for an etiologic role of perceived stress and life stressors in the development of chronic MDs. Database searches were conducted to identify prospective longitudinal studies that assessed perceived stress and life stressors in individuals without, or in the first 6 weeks of, musculoskeletal pain. The primary outcome was the development of a chronic MD. Methodologic quality was investigated using an adapted version of the Quality Assessment Tool for Observational Cohort studies and Cross-Sectional studies, and the strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Seven studies were included representing data from 6 independent cohorts. There was some evidence to support the etiologic role of perceived stress and life stressors in the development of arthritis (low quality) and chronic spinal pain (low quality). The limited number of studies, the poor quality of the evidence, and the heterogeneity of stress measures used across studies suggest that further high quality prospective studies are required to clarify the role of perceived stress and life stressors in the development of chronic MDs. PROSPERO: CRD42017059949 PERSPECTIVE: This review summarizes and critically appraises the evidence for the etiologic role of perceived stress and life stressors in the development of chronic MDs. The limited number of studies, the low quality of the evidence, and the heterogeneity across studies suggest that further research is needed on perceived stress and life stressors in MDs.

Made available in DSpace on 2019-10-06T16:25:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-01 National Health and Medical Research Council Objective: To investigate whether clinical tests used to detect motor control dysfunction can predict improvements in pain and disability in patients with chronic nonspecific low back pain (LBP) who have undergone an 8-week lumbar stabilization exercise program. Study Design: A prospective cohort study. Setting: Outpatient physical therapy university clinic. Participants: Seventy people with chronic nonspecific LBP were recruited, and 64 completed the exercise program (N=64). Interventions: The lumbar stabilization program was provided twice a week for 8 weeks. Main Outcome Measures: Pain intensity (11-point numerical rating scale) and disability (Roland Morris Disability Questionnaire) and clinical tests, such as the Deep Muscle Contraction (DMC) scale, Clinical Test of Thoracolumbar Dissociation (CTTD), and Passive Lumbar Extension (PLE) test. Univariate and multivariate linear regression models were used in the prediction analysis. Results: Mean changes in pain intensity and disability following the 8-week stabilization program were −3.8 (95% confidence interval [CI], −3.2 to −4.4) and −7.4 (95% CI, −6.3 to −8.5), respectively. Clinical test scores taken at baseline did not predict changes in pain and disability at 8-week follow-up. Conclusion: Our findings revealed that the DMC scale, CTTD, PLE test, clinical tests used to assess motor control dysfunction, do not predict improvements in pain and disability in patients with chronic nonspecific LBP following an 8-week lumbar stabilization exercise program. Physical Therapy Department Faculty of Science and Technology Sao Paulo State University (UNESP) Presidente Prudente Department of Physical Therapy Federal University of Minas Gerais (UFMG) Sydney School of Public Health Faculty of Medicine and Health The University of Sydney Neuroscience Research Australia Physical Therapy Department Faculty of Science and Technology Sao Paulo State University (UNESP) Presidente Prudente National Health and Medical Research Council: 1105040

Sensorimotor cortical activity is altered in both the immediate acute and chronic stages of musculoskeletal pain. However, these changes are opposite, with decreased cortical activity reported in experimentally induced acute pain (lasting minutes to hours), and increased cortical activity in chronic, clinical pain (lasting6 months). It is unknown whether sensorimotor cortical activity is altered in acute, clinical musculoskeletal pain (lasting4 weeks). In 36 individuals with acute, nonspecific, clinical low back pain (LBP) and 36 age- and sex-matched, pain-free controls, we investigated the processing of non-noxious afferent inputs using sensory evoked potentials (SEPs), as well as corticomotor excitability and organization of the primary motor cortex using transcranial magnetic stimulation. Processing of non-noxious sensory inputs was lower (smaller area of the N

Musculoskeletal pain is associated with altered motor control that, despite short-term benefit, is hypothesised to have long-term consequences, contributing to the development of chronic pain. However, data on how motor control is altered when pain is sustained beyond a transient event are scarce. Here, we investigated motor adaptation, and its relationship with corticomotor excitability, in the transition to sustained muscle pain. Twenty-eight healthy individuals were injected with nerve growth factor into the right extensor carpi radialis brevis muscle on days 0 and 2. Motor adaptation and corticomotor excitability were assessed on day -2, before injection on days 0 and 2, and again on days 4 and 14. Motor adaptation was quantified during a radial-ulnar movement as kinematic variability of wrist flexion-extension and pronation-supination, and as electromyographic (EMG) variability of extensor carpi radialis brevis activity. Pain, muscle soreness, and functional limitation were assessed from days 0 to 14. Pain, muscle soreness, and functional limitation were evident at days 2 and 4 (P < 0.001). Electromyographic variability reduced at days 4 and 14 (P < 0.04), with no change in kinematic variability (P = 0.9). However, data revealed variation in EMG and kinematic variability between individuals: some displayed increased motor variability, whereas others a decrease. Individuals who displayed an increase in EMG variability after 4 days of pain also displayed an increase in corticomotor excitability (r = 0.43, P = 0.034). These findings suggest individual adaptation of the motor system in the transition to sustained pain that could have implications for clinical musculoskeletal pain disorders.

To compare soleus spinal reflex excitability, presynaptic inhibition and recurrent inhibition between chronic ankle instability (CAI), acute Lateral Ankle Sprain coper (LAS-coper) and healthy populations. The relationship between spinal reflex excitability and pain and perceived instability in people with CAI was also examined.Cross-sectional laboratory experiment.Twelve individuals with CAI, twelve 'copers' and twelve healthy age, limb and gender-matched controls participated. Soleus H-reflex recruitment curves, pre-synaptic excitability and recurrent inhibition of the spinal-reflex pathway were examined during static double- and single-leg stance. Reporting of pain and perceived instability were used to perform a regression analysis on measures of soleus spinal excitability in people with CAI, LAS-coper and healthy controls.Soleus spinal reflex excitability was greater during single-leg stance in CAI compared to healthy and coper individuals (p=0.001). Pre-synaptic inhibition was three-times less in CAI participants compared to both healthy controls and copers (p=0.001). There were no differences between healthy and coper participants in spinal-level measures of sensorimotor control. Reports of pain explained 15-16% of the variance in soleus spinal reflex excitability and presynaptic inhibition during single and double-leg stance, while perceived instability explained 20% of the variance in spinal reflex during single leg stance only.CAI participants presented with an inability to suppress soleus spinal reflexes during tasks with increased postural threat; likely due to disinhibition of pre-synaptic mechanisms. Pain and perceived instability may contribute to changes in spinal-level sensorimotor control in CAI.

Objectives To explore the type of exercise prescribed by Australian health professionals for LBP, and whether the exercises prescribed are pain-free or into pain. Methods A survey of physiotherapists and exercise physiologists was conducted from all states/territories in Australia. The survey contained two chronic LBP vignettes with different pain mechanisms (dominant nociceptive or central sensitisation pain) and one acute LBP vignette. Respondents were asked if they would prescribe advice to stay active and exercise. If exercise was prescribed, respondents were asked to specify the type and pain provoking nature (exercise with no pain, exercise to the start of pain, exercise with pain at a tolerable level or exercise irrespective of pain). Results The response rate was 17%(218/1276). Most respondents prescribed advice to stay active(≥95%) and exercise(≥90%) for all vignettes. Irrespective of the vignette, several exercises were prescribed [aerobic (57–85% of clinicians), motor control (62–84% of clinicians), range of motion (72–75% of clinicians)]. Strengthening exercise was prescribed more for chronic(>60%) than acute LBP(23%). Irrespective of the exercise, between 20 and 25% of respondents prescribed pain-free exercise, between 71 and 79% of respondents prescribed exercise into pain, and ≤4% prescribed exercise irrespective of pain for acute and chronic LBP. Conclusions Several exercises are prescribed for LBP, irrespective of pain mechanism or duration, with more clinicians prescribing strengthening exercise for chronic than acute LBP. Most clinicians prescribed exercise into pain for acute and chronic LBP, irrespective of the exercise. Further research should determine which exercises are beneficial based on pain mechanism and duration, and whether exercise into pain should be prescribed for LBP.

Background Traditional transcranial magnetic stimulation mapping involves systematically delivering stimuli over a predefined grid. The pseudorandom walk method seeks to improve map acquisition times by abandoning the grid in favour of delivering stimuli randomly over a given area. Objectives To i) determine the minimum interstimulus interval (ISI) required for reliable mapping outcomes within and between sessions using the pseudorandom walk method and ii) assess the validity of the pseudorandom walk method by testing its equivalence with traditional mapping. Methods Maps collected using the pseudorandom walk method at four ISIs (4, 3, 2, and 1s) were compared to maps collected using traditional mapping in twenty healthy individuals. Outcomes included map area, volume, centre of gravity, mean MEP amplitude, and number of discrete peaks. Results and Conclusions The pseudorandom walk method was valid and reliable with a 2-second ISI for all outcomes except number of discrete peaks, which was less reliable than other measures.

Aberrant synaptic plasticity is hypothesised to underpin chronic pain. Yet, synaptic plasticity regulated by homeostatic mechanisms have received limited attention in pain. We investigated homeostatic plasticity in the human primary motor cortex (M1) of 21 healthy individuals in response to experimentally induced muscle pain for several days. Experimental pain was induced by injecting nerve growth factor into the muscle belly of the right extensor carpi radialis brevis muscle. Pain and disability were monitored until day 21. Homeostatic plasticity was induced on day 0, 2, 4, 6, and 14 in the left M1 using anodal transcranial direct stimulation (tDCS) applied for 7 and 5 min, separated by a 3-min rest period. Motor-evoked potentials (MEP) to transcranial magnetic stimulation assessed the homeostatic response. On days 0 and 14, MEPs increased following the first block of tDCS (p

Objective Low back pain is the leading contributor to the global disability burden. The Global Spine Care Initiative (GSCI) recommend patient-centred care to stem the cost of low back pain. One way to enhance patient-centred care is by better understanding what is relevant for people with low back pain. Exploring social media posts about low back pain could offer this insight and provide valuable information for health care professionals to facilitate active participation in patient-centred care. Methods We used an inductive content analysis method. In the form of social media posts, data on Twitter and Instagram were collected from June to August 2018. The posts were geo-targeted to Australia. We recorded the number of status broadcasts that contained a low back pain keyword and responses. We developed a codebook to describe the data and applied it to identify low back pain themes. Results We analysed 768 posts containing 457 status broadcasts and 311 responses. Almost half (49%) of status broadcasts about low back pain seemed to seek validation. Expressing sympathy (31%) was the most common response to a status broadcast about low back pain. There were no public responses to 76% of status broadcasts about low back pain. Our analysis yielded two core themes, “hear my pain” and “I feel for you". Conclusions Posts about low back pain on social media often seem to suggest that the person posting is seeking validation. Responses typically express sympathy or a shared experience; yet, there is no response to most social media posts about low back pain.

Objective Although acute pain has been shown to reduce corticomotor excitability, it remains unknown whether this response resolves over time or is related to symptom severity. Furthermore, acute pain research has relied upon data acquired from the cranial “hotspot,” which do not provide valuable information regarding reorganization, such as changes to the distribution of a painful muscle’s representation within M1. Using a novel, rapid transcranial magnetic stimulation (TMS) mapping method, this study aimed to 1) explore the temporal profile and variability of corticomotor reorganization in response to acute pain and 2) determine whether individual patterns of corticomotor reorganization are associated with differences in pain, sensitivity, and somatosensory organization. Methods Corticomotor (TMS maps), pain processing (pain intensity, pressure pain thresholds), and somatosensory (two-point discrimination, two-point estimation) outcomes were taken at baseline, immediately after injection (hypertonic [n = 20] or isotonic saline [n = 20]), and at pain resolution. Follow-up measures were recorded every 15 minutes until 90 minutes after injection. Results Corticomotor reorganization persisted at least 90 minutes after pain resolution. Corticomotor depression was associated with lower pain intensity than was corticomotor facilitation (r = 0.47 [P = 0.04]). These effects were not related to somatosensory reorganization or peripheral sensitization mechanisms. Conclusions Individual patterns of corticomotor reorganization during acute pain appear to be related to symptom severity, with early corticomotor depression possibly reflecting a protective response. These findings hold important implications for the management and potential prevention of pain chronicity. However, further research is required to determine whether these adaptations relate to long-term outcomes in clinical populations.

OBJECTIVES Explore the moderating effects of psychological or social variables on associations between biomarkers of inflammation/stress and clinical reports of pain. METHODS This is a cross-sectional exploratory study. Data were drawn from the Systematic Merging of Biology, Mental Health and Environment (SYMBIOME) longitudinal study (clinicaltrials.gov ID no. NCT02711085). Eligible participants were adults who presented to an Urgent Care Centre in Ontario, Canada within 3 weeks of a noncatastrophic musculoskeletal trauma (no surgery or hospitalization). A questionnaire package was given that included the Brief Pain Inventory (capturing pain severity and pain interference) and relevant person-level variables. Blood samples were also drawn for serum analysis of 8 target biomarkers (brain-derived neurotrophic factor, transforming growth factor beta 1 [TGF-β1], c-reactive protein, tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-10, and cortisol). RESULTS Employment before trauma (employed for pay/not employed for pay) fully moderated the association between tumor necrosis factor-α and pain severity (∆R2=4.4%). Pre-existing psychopathology (yes/no) fully moderated the association between TGF-β1 and pain severity (∆R2=8.0%). Sex (male/female) fully moderated the association between c-reactive protein and pain severity (∆R2=6.3%). A pre-existing pain condition (yes/no) was significantly associated with worse pain interference (R2=7.2%), and partially moderated the effect of IL-1β on pain interference (∆R2=6.9%). Higher peritraumatic life stress significantly explained 8.9% of variance in pain interference alone, and partially moderated the effect of TGF-β1 on interference (∆R2=4.4%). DISCUSSION Simple bivariate associations between blood-based markers and clinical symptoms are unlikely to reveal meaningful relationships. However, when stratified by existing person-level or "metadata" variables, an association may exist for at least 1 clinically relevant subgroup.

IntroductionThere is a gap between the care people with knee osteoarthritis (OA) should receive according to evidence-based guidelines and the care they do receive. This feasibility study aims to test the feasibility of developing and implementing a codesigned, physiotherapy-led, multidisciplinary, evidence-based model of care for knee OA, among community physiotherapy practices in Australia, where community practice is defined as a professional physiotherapy business that is not controlled or paid for by the government.Methods and analysisA mixed-methods quasi-experimental (pre/postintervention) study. In the preintervention phase, all consented physiotherapists working in nine metropolitan-based, community physiotherapy practices, and 26 patients with knee OA will be recruited. Patients will be recruited from all practices by the physiotherapists, using the outlined inclusion/exclusion criteria. An audit of physiotherapy treatment notes will occur using a proforma, to gain an understanding of current community physiotherapy treatment and documentation. Patient and physiotherapist interviews will be conducted to determine current practice for the management of knee OA. A codesign phase will follow, where a model of care will be developed by researchers, patients, clinical staff, members of the public and other stakeholders, based on current guidelines for conservative management of knee OA. In the postintervention phase, a further 26 patients will be recruited, and the assessment process repeated to determine whether there is a change in practice. The feasibility outcome measures are: (1) number of patients who are recorded as receiving care according to current evidence-based guidelines; (2) number of patients who have patient-reported outcomes incorporated into their assessment and management plan; and (3) acceptability of the developed model to patients and physiotherapists. The clinical outcomes will include assessment of patient-reported outcome measures (pain, function, etc) in the preintervention and postintervention phases (baseline and 12 weeks) to assess trends towards change in participant symptoms.Ethics and disseminationEthical approval has been obtained from the University of New South Wales human ethics committee (approval number HC180864, approval period 6 February 2019 to 5 February 2024). The preintervention stage of this study is complete. The next stage is to implement the intervention and compare outcomes between the preintervention and postintervention phases. The results will be disseminated via peer-reviewed publications and presentations at conferences.Trial registration numberThe preintervention phase of the study is retrospectively registered at ClinicalTrials.gov with registration number: ACTRN12620000188932. The intervention and postintervention phase of the study is prospectively registered at ClinicalTrials.gov with registration number: ACTRN12620000218998.

Introduction: The primary motor cortex (M1) is a key brain region implicated in pain processing. Here, we present a protocol for a review that aims to synthesise and critically appraise the evidence for the effect of experimentalpain on M1 function. Methods/Analysis: A systematic review and meta-analysis will be conducted. Electronic databases will be searched using a predetermined strategy. Studies published before April 2020 that investigate the effects of experimentally induced pain on corticomotor excitability (CME) in healthy individuals will be included if they meet eligibility criteria. Study identification, data extraction andrisk of bias assessment will be conducted by two independent reviewers, with a third reviewer consulted for any disagreements. The primary outcomes will include group level changes in CME and intracortical, transcortical and sensorimotor modulators of CME. A separate analysis using individual data will also be conducted to explore individual differences in CME in response to experimental pain. The meta-analysis will consider the following factors: pain model (transient, tonic, transitional pain), type of painful tissue (cutaneous, musculoskeletal), time points of outcome measures(during or after recovery from pain) and localisation of pain(target area, control area). Discussion: This review will provide a comprehensive understanding of the mechanisms within M1 that mediate experimentally induced pain, both on a group and individual level. Registration Number: The systematic review is registered with the International Prospective Register of Systematic Reviews (#CRD42020173172)

The left dorsolateral prefrontal cortex (DLPFC) is involved in the experience and modulation of pain, and may be an important node linking pain and cognition. Repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC can reduce chronic and experimental pain. However, whether left DLPFC rTMS can influence the development of chronic pain is unknown. Using repeated intramuscular injection of nerve growth factor to induce the development of sustained muscle pain (lasting weeks), 30 healthy individuals were randomized to receive 5 consecutive daily treatments of active or sham left DLPFC rTMS, starting before the first nerve growth factor injection on day 0. Muscle soreness and pain severity were collected daily for 14 days and disability on every alternate day. Before the first and 1 day after the last rTMS session, anxiety, depression, affect, pain catastrophizing, and cognitive performance on the attention network test were assessed. Left DLPFC rTMS treatment compared with sham was associated with reduced muscle soreness, pain intensity, and painful area (P < 0.05), and a similar trend was observed for disability. These effects were most evident during the days rTMS was applied lasting up to 3 days after intervention. Depression, anxiety, pain catastrophizing, and affect were unchanged. There was a trend toward improved cognitive function with rTMS compared with sham (P = 0.057). These data indicate that repeated left DLPFC rTMS reduces the pain severity in a model of prolonged muscle pain. The findings may have implications for the development of sustained pain in clinical populations.