The Mediating Role of Pain Cognitions and Pain Sensitivity in the Treatment Effect of Perioperative Pain Neuroscience Education in People Undergoing Surgery for Lumbar Radiculopathy.

Though perioperative pain neuroscience education (PPNE) positively influences patients' surgical outcomes, little is known about the mechanisms behind this treatment's success. Therefore, this study aims to evaluate the potential mediating role of pain cognitions and pain sensitivity in the treatment effect of PPNE on postoperative quality of life in people undergoing surgery for lumbar radiculopathy. This secondary analysis uses data from 120 participants of a randomized controlled trial who were randomized to receive either PPNE or perioperative biomedical education before undergoing surgery for lumbar radiculopathy. Quality of life was assessed 1-year postsurgery using the short form 36-item health survey (SF36) physical and mental component scores. Potential mediators included pain cognitions (ie, kinesiophobia, pain catastrophizing, and hypervigilance) and pain sensitivity (ie, endogenous nociceptive modulation), assessed 6 weeks postsurgery. Mediation models were constructed using structural equation modeling, and 95% confidence intervals (CIs) were calculated using 10,000 bootstrap samples. Analyses show a significant total effect for PPNE (estimate = .464, 95% CI [.105, .825]) and a significant indirect effect via pain catastrophizing on the SF36 physical component (estimate = .124, 95% CI [.001, .293]). No mediating effect was found through the remaining pain cognitions or pain sensitivity measures. Also, no potential mediators were identified for the treatment effect of PPNE on the SF36 mental component. Our findings suggest that pain catastrophizing mediates the treatment effect of PPNE on physical health-related quality of life in people undergoing surgery for lumbar radiculopathy. PERSPECTIVE: This secondary analysis identified pain catastrophizing as a mediator for PPNE in people undergoing surgery for lumbar radiculopathy. More so, its findings indicate that this educational intervention can enhance the postoperative physical health-related quality of life of these patients by addressing their catastrophizing thoughts. TRIAL REGISTRATION: Clinicaltrials.gov (NCT02630732).

Influence of Preoperative Pain, Cognitions, and Quantitative Sensory Testing Measures on the Effects of Perioperative Pain Neuroscience Education for People Receiving Surgery for Lumbar Radiculopathy: Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: To explore whether preoperative pain intensity, pain cognitions, and quantitative sensory measures influence the established effectiveness of perioperative pain neuroscience education (PPNE) on health-related quality of life at 1 year after surgery for lumbar radiculopathy. DESIGN: Secondary analysis of a triple-blinded randomized controlled trial. METHODS: Participants (n = 90) were Dutch-speaking adults (18-65 years) who were scheduled for surgery for lumbar radiculopathy in 3 Belgian hospitals. They were randomized (1:1) to receive PPNE (n = 41) or perioperative biomedical education (n = 49). Linear mixed models were built for health-related quality of life (ie, SF-6D utility values, Physical and Mental Component of the 36-item Short Form Health Survey) using the following independent variables: therapy, time, and preoperative scores for back and leg pain intensity, pain catastrophizing, kinesiophobia, hypervigilance, and quantitative sensory measures. RESULTS: The impact of PPNE on SF-6D utility values over time was influenced by kinesiophobia (F = 3.30, P = .02) and leg pain intensity (F = 3.48, P = .02). Regardless of the intervention, back pain intensity negatively influenced SF-6D values over time (F = 3.99, P = .009). The Physical Component scores were negatively impacted by back pain intensity (F = 9.08, P = .003) and were influenced over time by leg pain intensity (F = 2.87, P = .04). The Mental Component scores were negatively impacted by back pain intensity (F = 6.64, P = .01) and pain catastrophizing (F = 5.42, P = .02), as well as hypervigilance (F = 3.16, P = .03) and leg pain intensity (F = 3.12, P = .03) over time. CONCLUSION: PPNE may be more effective than perioperative biomedical education in improving postoperative health utility values in patients who reported higher kinesiophobia and leg pain intensity before surgery for lumbar radiculopathy. J Orthop Sports Phys Ther 2024;54(4):1-10. Epub 8 January 2024. doi:10.2519/jospt.2024.12051.

Effect of perioperative pain neuroscience education in people undergoing surgery for lumbar radiculopathy: a multicentre randomised controlled trial.

BACKGROUND: Perioperative education should be improved to decrease unfavourable outcomes after lumbar surgery. This trial aimed to compare effectiveness in terms of pain, quality of life, pain cognition, surgical experience, healthcare use, work resumption, and cost-effectiveness of perioperative pain neuroscience education (PPNE) vs traditional biomedical education (perioperative biomedical education [PBE]) in people undergoing surgery for lumbar radiculopathy. METHODS: In this multicentre RCT (ClinicalTrials.gov: NCT02630732), patients undergoing surgery for lumbar radiculopathy in three Belgian hospitals were randomised to receive PPNE or PBE. Both groups received one preoperative and one postoperative one-to-one education session and a booklet (balanced interventions), with an essentially different content (PPNE: biopsychosocial; PBE: biomedical). Pain was the primary outcome (Visual Analogue Scales+quantitative sensory testing). Assessments were at 3 days, 6 weeks, and 6 and 12 months after surgery. RESULTS: Between March 2016 and April 2020, participants were randomly assigned to PPNE (n=58) or PBE (n=62). At 12 months, PPNE did not lead to significantly better pain outcomes, but it did result in more favourable 36-item Short Form Health Survey physical component (additional increase: 46.94; 95% confidence interval [CI]: 14.16-79.73; medium effect), Tampa Scale of Kinesiophobia (additional decrease: 3.15; 95% CI: 0.25-6.04; small effect), and Pain Catastrophising Scale (additional decrease: 6.18; 95% CI: 1.97-10.39; medium effect) scores. Females of the PPNE group showed higher probability for work resumption (95% vs 60% in the PBE group). PPNE was cost-effective compared with PBE (incremental costs: €-2732; incremental quality-adjusted life years: 0.012). CONCLUSIONS: Perioperative pain neuroscience education showed superior clinical and cost-effectiveness than perioperative biomedical education in people undergoing surgery for lumbar radiculopathy. CLINICAL TRIAL REGISTRATION: NCT02630732.

Exploring Associations between Healthcare Use and Demographics, Pain and Pain Cognitions in People Scheduled for Surgery for Lumbar Radiculopathy: A Cross-Sectional Study.

This cross-sectional study explored associations between demographics, pain intensity and cognitions on the one hand and healthcare use (HCU) on the other hand in people undergoing surgery for lumbar radiculopathy. HCU during the 2 months preceding surgery was evaluated using a retrospective questionnaire. Demographics included sex, age and level of education and equivalent income. Back and leg pain intensity were evaluated using a visual analogue scale. Pain cognitions were assessed with the Tampa scale of kinesiophobia, the pain catastrophizing scale and the pain vigilance and awareness questionnaire. The sample comprised 120 participants (52% males; 49 years (Quartile (Q)1-Q3: 37.3-57.43)). The number of visits to the general practitioner was associated with sex (incidence rate ratio (IRR) for males = 0.811; p = 0.050), pain catastrophizing (IRR = 1.010; p = 0.041), pain magnification (IRR = 1.058; p = 0.004) and leg pain intensity (IRR = 1.004; p = 0.038). The number of neurosurgeon visits was associated with level of education (IRR moderate education = 1.518; p = 0.016 (reference: low education)). Receiving zero physiotherapy visits was associated with higher back pain intensity (Beta = 0.018; p = 0.028). Highest level of analgesics used was associated with sex (IRR for males = 0.502; p = 0.047) and leg pain (IRR = 1.014; p = 0.034). Only the association between general practitioner visits and pain magnification remained significant in multivariable analyses (IRR = 1.061; p = 0.033). The results suggest a rather indirect relationship between HCU and demographics, pain intensity and cognitions, involving a potential interplay between several patient- and healthcare system-related factors.

Experimental Pain Measurements Do Not Relate to Pain Intensity and Pain Cognitions in People Scheduled for Surgery for Lumbar Radiculopathy.

OBJECTIVE: The present cross-sectional study aims to unravel associations of pain intensity and cognitions with quantitative sensory testing in people scheduled for surgery for lumbar radiculopathy. Additionally, insight will be provided into the presence of dysfunctional nociceptive processing and maladaptive pain cognitions in this population. DESIGN: Cross-sectional study. SETTING: Data from three hospitals in Belgium. SUBJECTS: The final sample comprised 120 participants with lumbar radiculopathy scheduled for surgery, included between March 2016 and April 2019. METHODS: Self-reported pain intensity was assessed on a visual analog scale, and pain cognitions were assessed with self-reported questionnaires (Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia, and Pain Vigilance and Awareness Questionnaire). Quantitative sensory testing (detection thresholds, pain thresholds, temporal summation, and conditioned pain modulation) was evaluated, as well. RESULTS: Evidence was found for the presence of an impaired inhibitory response to nociceptive stimuli and maladaptive pain cognitions in this population. Kinesiophobia was found to be present to a maladaptive degree in the majority of the patients (n = 106 [88%]). Significant, but weak, associations between electrical pain thresholds at the sural nerves and leg pain intensity (sural nerve symptomatic side: r = -0.23; P = 0.01; non-symptomatic side: r = -0.22; P = 0.02) and kinesiophobia levels (sural nerve non-symptomatic side: r = -0.26; P = 0.006) were identified. CONCLUSIONS: Electrical detection thresholds and correlates for endogenous nociceptive facilitation and inhibition were not found to be related to any of the pain cognitions or to pain intensity in people scheduled to undergo surgery for lumbar radiculopathy.

Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and Fibromyalgia.

BACKGROUND: Catechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathophysiological features of Chronic Fatigue Syndrome and Fibromyalgia (CFS/FM). We aimed to determine the interactions between genetic and epigenetic mechanisms regulating COMT and its influence on inflammatory markers and symptoms in patients with CFS/FM. METHODS: A case-control study with repeated-measures design was used to reduce the chance of false positive and increase the power of our findings. Fifty-four participants (28 patients with CFS/FM and 26 controls) were assessed twice within 4 days. The assessment included clinical questionnaires, neurophysiological assessment (pain thresholds, temporal summation, and conditioned pain modulation), and blood withdrawal in order to assess rs4818, rs4633, and rs4680 COMT polymorphisms and perform haplotype estimation, DNA methylation in the COMT gene (both MB-COMT and S-COMT promoters), and cytokine expression (TNF-α, IFN-γ, IL-6, and TGF-ß). RESULTS: COMT haplotypes were associated with DNA methylation in the S-COMT promoter, TGF-ß expression, and symptoms. However, this was not specific for one condition. Significant between-group differences were found for increased DNA methylation in the MB-COMT promoter and decreased IFN-γ expression in patients. DISCUSSION: Our results are consistent with basic and clinical research, providing interesting insights into genetic-epigenetic regulatory mechanisms. MB-COMT DNA methylation might be an independent factor contributing to the pathophysiology of CFS/FM. Further research on DNA methylation in complex conditions such as CFS/FM is warranted. We recommend future research to employ a repeated-measure design to control for biomarkers variability and within-subject changes.

Health-related quality of life deviations from population norms in patients with lumbar radiculopathy: associations with pain, pain cognitions, and endogenous nociceptive modulation.

PURPOSE: The primary goal of this study was to compare the health-related quality of life (HRQoL) of people with lumbar radiculopathy to age- and sex-adjusted population norms. Additionally, it aimed to explore the associations between the HRQoL difference scores and measures related to pain cognitions, pain intensity, and endogenous nociceptive modulation. METHODS: Using answers from the Short Form 36-item Health Survey and UK population norms, SF-6D difference scores were calculated. A one-sample t test was used to assess the SF-6D difference scores. Univariate and multivariate regression analyses were used to assess the associations between SF-6D difference scores and pain intensity [Visual Analogue Scale (VAS) for back and leg pain], pain cognitions [Pain Catastrophizing Scale (PCS), Tampa Scale for Kinesiophobia (TSK), Pain Vigilance and Awareness Questionnaire (PVAQ)], and correlates for endogenous nociceptive modulation using quantitative sensory testing. RESULTS: One hundred and twenty people with lumbar radiculopathy scheduled for surgery were included in this study. The mean SF-6D difference score of - 0.26 [SD = 0.09] was found to be significantly less than 0 [95%CI: - 0.27 to - 0.24]. Univariate analyses showed a significant influence from PCS, TSK, and PVAQ on the SF-6D difference scores. The final multivariate regression model included PCS and PVAQ, with only PCS maintaining a statistically significant regression coefficient [b = - 0.002; 95% CI: - 0.004 to - 0.001]. CONCLUSION: People diagnosed with lumbar radiculopathy report significantly lower HRQoL scores when compared with age- and sex-adjusted UK norm values. Even though all examined pain cognitions were found to have a significant association, pain catastrophizing showed the most significant relation to the SF-6D difference scores. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier No. NCT02630732. Date of registration: November 25, 2015.

The Impact of Parental Pain-attending and Non-pain-attending Responses on Child Pain Behavior in the Context of Cancer-related Painful Procedures: The Moderating Role of Parental Self-oriented Distress.

OBJECTIVES: Literature has demonstrated inconsistent findings regarding the impact of parental responses on child pain-related outcomes. Yet, research into factors that may underlie inconsistent findings regarding the variable impact of parental responses is lacking. The current study investigated the moderating role of parental distress in understanding the impact of parental pain-attending (eg, reassuring the child) and non-pain-attending (eg, distracting the child with humor) responses on child pain behavior (eg, crying). METHODS: Children (18 y and younger) with leukemia, undergoing a lumbar puncture (LP) and/or bone marrow aspiration procedure, and one of their parents, were recruited from the Pediatric Ghent University Hospital. Parent-child interactions were videotaped after the procedure allowing coding of parental responses and child pain behavior. Parents self-reported on experienced personal distress. RESULTS: Participants consisted of 42 children (24 boys, 18 girls) with leukemia and one of their parents. Children were 0.6 to 15 (7.08±4.39) years old. Findings indicated a positive association between parental pain-attending and child pain behavior, but only when parents reported high levels of distress (ß=0.56, P=0.001). No association was observed for parents reporting low levels of distress (ß=-0.09, ns). Parental non-pain-attending responses contributed to lower child pain behavior (ß=-0.24, P=0.045), independently of parental distress (ß=-0.07, ns). DISCUSSION: The current findings point to the moderating role of parental distress in understanding the impact of parental responses on child pain behavior and highlight the importance of interventions targeting parental emotion regulation to promote optimal child pain outcomes.

Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine.

Chronic pain is a leading cause of disability globally and associated with enormous health-care costs. The discrepancy between the extent of tissue damage and the magnitude of pain, disability, and associated symptoms represents a diagnostic challenge for rheumatology specialists. Central sensitisation, defined as an amplification of neural signalling within the CNS that elicits pain hypersensitivity, has been investigated as a reason for this discrepancy. Features of central sensitisation have been documented in various pain conditions common in rheumatology practice, including fibromyalgia, osteoarthritis, rheumatoid arthritis, Ehlers-Danlos syndrome, upper extremity tendinopathies, headache, and spinal pain. Within individual pain conditions, there is substantial variation among patients in terms of presence and magnitude of central sensitisation, stressing the importance of individual assessment. Central sensitisation predicts poor treatment outcomes in multiple patient populations. The available evidence supports various pharmacological and non-pharmacological strategies to reduce central sensitisation and to improve patient outcomes in several conditions commonly seen in rheumatology practice. These data open up new treatment perspectives, with the possibility for precision pain medicine treatment according to pain phenotyping as a logical next step. With this view, studies suggest the possibility of matching non-pharmacological approaches, or medications, or both to the central sensitisation pain phenotypes.

The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease: Potential Role of Autonomic Regulation and Epigenetic Mechanisms.

Oxidative stress can be induced by various stimuli and altered in certain conditions, including exercise and pain. Although many studies have investigated oxidative stress in relation to either exercise or pain, the literature presents conflicting results. Therefore, this review critically discusses existing literature about this topic, aiming to provide a clear overview of known interactions between oxidative stress, exercise, and pain in healthy people as well as in people with chronic pain, and to highlight possible confounding factors to keep in mind when reflecting on these interactions. In addition, autonomic regulation and epigenetic mechanisms are proposed as potential mechanisms of action underlying the interplay between oxidative stress, exercise, and pain. This review highlights that the relation between oxidative stress, exercise, and pain is poorly understood and not straightforward, as it is dependent on the characteristics of exercise, but also on which population is investigated. To be able to compare studies on this topic, strict guidelines should be developed to limit the effect of several confounding factors. This way, the true interplay between oxidative stress, exercise, and pain, and the underlying mechanisms of action can be revealed and validated via independent studies.

Electroencephalography During Nociceptive Stimulation in Chronic Pain Patients: A Systematic Review.

BACKGROUND: With its high temporal resolution, electroencephalography (EEG), a technique that records electrical activity of cortical neuronal cells, is a potentially suitable technique to investigate human somatosensory processing. By using EEG, the processing of (nociceptive) stimuli can be investigated, along with the functionality of the nociceptive pathway. Therefore, it can be applied in chronic pain patients to objectify whether changes have occurred in nociceptive processing. Typically, so-called event-related potential (ERP) recordings are used, where EEG signals are recorded in response to specific stimuli and characterized by latency and amplitude. OBJECTIVE: To summarize whether differences in somatosensory processing occur between chronic pain patients and healthy controls, measured with ERPs, and determine whether this response is related to the subjective pain intensity. DESIGN: Systematic review. SETTING AND METHODS: PubMed, Web of Science, and Embase were consulted, and 18 case-control studies were finally included. SUBJECTS: The chronic pain patients suffered from tension-type headache, back pain, migraine, fibromyalgia, carpal tunnel syndrome, prostatitis, or complex regional pain syndrome. RESULTS: Chronic neuropathic pain patients showed increased latencies of the N2 and P2 components, along with a decreased amplitude of the N2-P2 complex, which was also obtained in FM patients with small fiber dysfunction. The latter also showed a decreased amplitude of the N2-P3 and N1-P1 complex. For the other chronic pain patients, the latencies and the amplitudes of the ERP components did not seem to differ from healthy controls. One paper indicated that the N2-P3 peak-to-peak amplitude correlates with the subjective experience of the stimulus. CONCLUSIONS: Differences in ERPs with healthy controls can mostly be found in chronic pain populations that suffer from neuropathic pain or where fiber dysfunction is present. In chronic pain populations with other etiological mechanisms, limited differences were found or agreed upon across studies.

DNA Methylation and Brain-Derived Neurotrophic Factor Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Comorbid Fibromyalgia.

OBJECTIVE: The epigenetics of neurotrophic factors holds the potential to unravel the mechanisms underlying the pathophysiology of complex conditions such as chronic fatigue syndrome (CFS). This study was undertaken to explore the role of brain-derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM). METHODS: A repeated-measures study was conducted in 54 participants (28 patients with CFS/FM and 26 matched healthy controls). Participants underwent a comprehensive assessment, including questionnaires, sensory testing, and blood withdrawal. Serum BDNF (sBDNF) protein levels were measured using enzyme-linked immunosorbent assay, while polymorphism and DNA methylation were measured in blood using pyrosequencing technology. To assess the temporal stability of the measures, participants underwent the same assessment twice within 4 days. RESULTS: Repeated-measures mixed linear models were used for between-group analysis, with mean differences and 95% confidence intervals (95% CIs) shown. Compared to controls, serum BNDF was higher in patients with CFS/FM (F = 15.703; mean difference 3.31 ng/ml [95% CI 1.65, 4.96]; P = 0.001), whereas BDNF DNA methylation in exon 9 was lower (F = 7.543; mean difference -2.16% [95% CI -3.93, -0.83]; P = 0.007). BDNF DNA methylation was mediated by the Val66Met (rs6265) polymorphism. Lower methylation in the same region predicted higher sBDNF levels (F = 7.137, ß = -0.408 [95% CI -0.711, -0.105]; P = 0.009), which in turn predicted participants' symptoms (F = 14.410, ß = 3.747 [95% CI 1.79, 5.71]; P = 0.001) and widespread hyperalgesia (F = 4.147, ß = 0.04 [95% CI 0.01, 0.08]; P = 0.044). CONCLUSION: Our findings indicate that sBDNF levels are elevated in patients with CFS/FM and that BDNF methylation in exon 9 accounts for the regulation of protein expression. Altered BDNF levels might represent a key mechanism explaining CFS/FM pathophysiology.

The influence of nociceptive and neuropathic pain states on the processing of acute electrical nociceptive stimulation: A dynamic causal modeling study.

INTRODUCTION: Despite the worldwide increase in prevalence of chronic pain and the subsequent scientific interest, researchers studying the brain and brain mechanisms in pain patients have not yet clearly identified the exact underlying mechanisms. Quantifying the neuronal interactions in electrophysiological data could help us gain insight into the complexity of chronic pain. Therefore, the aim of this study is to examine how different underlying pain states affect the processing of nociceptive information. METHODS: Twenty healthy participants, 20 patients with non-neuropathic low back-related leg pain and 20 patients with neuropathic failed back surgery syndrome received nociceptive electrical stimulation at the right sural nerve with simultaneous electroencephalographic recordings. Dynamic Causal Modeling (DCM) was used to infer hidden neuronal states within a Bayesian framework. RESULTS: Pain intensity ratings and stimulus intensity of the nociceptive stimuli did not differ between groups. Compared to healthy participants, both patient groups had the same winning DCM model, with an additional forward and backward connection between the somatosensory cortex and right dorsolateral prefrontal cortex. DISCUSSION: The additional neuronal connection with the prefrontal cortex as seen in both pain patient groups could be a reflection of the higher attention towards pain in pain patients and might be explained by the higher levels of pain catastrophizing in these patients. CONCLUSION: In contrast to the similar pain intensity ratings of an acute nociceptive electrical stimulus between pain patients and healthy participants, the brain is processing these stimuli in a different way.

Electrical (Pain) Thresholds and Conditioned Pain Modulation in Patients with Low Back-Related Leg Pain and Patients with Failed Back Surgery Syndrome: A Cross-Sectional Pilot Study.

OBJECTIVE: When evaluating sensory dysfunctions and pain mechanisms in patients with low back pain (LBP), a specific subgroup of patients with radicular symptoms is often excluded. Comparative studies that evaluate sensory sensitivity in patients with a dominant nociceptive and neuropathic pain component are rarely performed. Therefore, the goal of this study was to examine differences in electrical thresholds and conditioned pain modulation (CPM) between patients with low back-related leg pain (LBRLP) and patients with failed back surgery syndrome (FBSS). DESIGN: Cross-sectional study. SETTING: University Hospital Brussels. SUBJECTS: Twenty-one patients with LBRLP and 21 patients with FBSS were included. METHODS: Electrical detection thresholds (EDTs), electrical pain thresholds (EPTs), and CPM were evaluated on the symptomatic and nonsymptomatic sides. Within- and between-group differences were evaluated for all parameters. RESULTS: No between-group differences were found for EDT and EPT at both sides. On the nonsymptomatic side, a significantly lower CPM effect was found in the FBSS group (P = 0.04). The only significant within-group difference was an increased EDT at the symptomatic side in patients with FBSS (P = 0.01). CONCLUSIONS: LBP patients with a primary neuropathic pain component revealed altered detection sensitivity at the symptomatic side, without severe indications for altered nociceptive processing, compared with LBP patients without a dominant neuropathic pain component. Endogenous modulation is functioning in LBP patients, although it is possible that it might only be functioning partially in patients with a dominant neuropathic pain component.

Lifestyle and Chronic Pain across the Lifespan: An Inconvenient Truth?

Chronic pain has a tremendous personal and socioeconomic impact and remains difficult to treat. Therefore, it is important to provide an update on the current understanding regarding lifestyle factors in people with chronic pain across the lifespan. Lifestyle factors such as physical (in)activity, sedentary behavior, stress, poor sleep, unhealthy diet, and smoking are associated with chronic pain severity and sustainment. This applies to all age categories, that is, chronic pain across the lifespan. Yet current treatment options often do not or only partly address the many lifestyle factors associated with chronic pain or attempt to address them in a standard format rather than providing an individually tailored multimodal lifestyle intervention. The evidence regarding lifestyle factors is available in adults, but limited in children and older adults having chronic pain, providing important avenues for future research. In conclusion, it is proposed that treatment approaches for people with chronic pain should address all relevant lifestyle factors concomitantly in an individually-tailored multimodal intervention. Ultimately, this should lead to improved outcomes and decrease the psychological and socioeconomic burden of chronic pain. Level of Evidence: IV.

Epigenetic and miRNA Expression Changes in People with Pain: A Systematic Review.

Accumulating evidence suggests that epigenetic mechanisms may hold great potential in the field of pain. We systematically reviewed the literature exploring epigenetic mechanisms in people with pain. Four databases have been interrogated: MEDLINE, The Cochrane Central Register of Controlled Trial, Scopus, and Web of Science, following PRISMA guidelines in conducting study selection and assessment. Thirty-seven studies were included. Studies explored epigenetics in conditions such as fibromyalgia, CRPS, neuropathies, or osteoarthritis. Research focussed on genome-wide and gene-specific DNA methylation, and miRNA expression. Bioinformatics analyses exploring miRNA-associated molecular pathways were also performed. Several genes already known for their role in pain (BDNF, HDAC4, PRKG1, IL-17, TNFRSF13B, etc.), and several miRNAs linked to inflammatory regulation, nociceptive signalling and protein kinases functions have been found to differ significantly between people with chronic pain and healthy controls. Although the studies included were cross-sectional in nature, and no conclusion on causal links between epigenetic changes and pain could be drawn, we summarised the large amount of data available in literature on the topic, highlighting results that have been replicated by independent investigations. The field of pain epigenetics appears very exciting and has all the potential to lead to remarkable scientific advances. However, high-quality, well-powered, longitudinal studies are warranted. PERSPECTIVE: Though more high-quality research is needed, available research exploring epigenetic mechanisms or miRNAs in people with pain shows that genes regulating synaptic plasticity and excitability, protein kinases, and elements of the immune system might hold great potential in understanding the pathophysiology of different conditions.

A Modern Pain Neuroscience Approach in Patients Undergoing Surgery for Lumbar Radiculopathy: A Clinical Perspective.

Around 20% of patients undergoing surgery for lumbar radiculopathy develop chronic pain after surgery, leading to high socioeconomic burden. Current perioperative interventions, including education and rehabilitation, are not always effective in preventing prolonged or chronic postoperative pain and disability. Here, a shift in educational intervention from a biomedical towards a biopsychosocial approach for people scheduled for lumbar surgery is proposed. Pain neuroscience education (PNE) is a biopsychosocial approach that aims to decrease the threat value of pain by reconceptualizing pain and increasing the patient's knowledge about pain. This paper provides a clinical perspective for the provision of perioperative PNE, specifically developed for patients undergoing surgery for lumbar radiculopathy. Besides the general goals of PNE, perioperative PNE aims to prepare the patient for postsurgical pain and how to cope with it.

Determinants and Variations of Hospital Costs in Patients With Lumbar Radiculopathy Hospitalized for Spinal Surgery.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to determine hospital costs related to surgery for lumbar radiculopathy and identify determinants of intramural costs based on minimal hospital and claims data. SUMMARY OF BACKGROUND DATA: Costs related to the initial hospitalization of patients undergoing surgery for lumbar radiculopathy make up the major part of direct health care expenditure in this population. Identifying factors influencing intramural costs can be beneficial for health care policy makers, and clinicians working with patients with lumbar radiculopathy. METHODS: The following data were collected from the University Hospital Brussels data warehouse for all patients undergoing surgery for lumbar radiculopathy in 2016 (n = 141): age, sex, primary diagnosis, secondary diagnoses, type of surgery, severity of illness (SOI), admission and discharge date, type of hospital admission, and all claims incurred for the particular hospital stay. Descriptive statistics for total hospital costs were performed. Univariate analyses were executed to explore associations between hospital costs and all other variables. Those showing a significant association (P < 0.05) were included in the multivariate general linear model analysis. RESULTS: Mean total hospital costs were &OV0556; 5016 ±â€Š188 per patient. Costs related to the actual residence (i.e., "hotel costs") comprised 53% of the total hospital costs, whereas 18% of the costs were claimed for the surgical procedure. Patients with moderate/major SOI had 44% higher hospital costs than minor SOI (P = 0.01). Presence of preadmission comorbidities incurred 46% higher costs (P = 0.03). Emergency procedures led to 72% higher costs than elective surgery (P < 0.001). Patients receiving spinal fusion had 211% higher hospital costs than patients not receiving this intervention (P < 0.001). CONCLUSION: Hospital costs in patients receiving surgery for lumbar radiculopathy are influenced by SOI, the presence of preadmission comorbidities, type of hospital admission (emergency vs. elective), and type of surgical procedure. LEVEL OF EVIDENCE: 3.

Relationship Between Exercise-induced Oxidative Stress Changes and Parasympathetic Activity in Chronic Fatigue Syndrome: An Observational Study in Patients and Healthy Subjects.

PURPOSE: Oxidative stress has been proposed as a contributor to pain in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). During incremental exercise in patients with ME/CFS, oxidative stress enhances sooner and antioxidant response is delayed. We explored whether oxidative stress is associated with pain symptoms or pain changes following exercise, and the possible relationships between oxidative stress and parasympathetic vagal nerve activity in patients with ME/CFS versus healthy, inactive controls. METHODS: The present study reports secondary outcomes from a previous work. Data from 36 participants were studied (women with ME/CFS and healthy controls). Subjects performed a submaximal exercise test with continuous cardiorespiratory monitoring. Levels of thiobarbituric acid-reactive substances (TBARSs) were used as a measure of oxidative stress, and heart rate variability was used to assess vagal activity. Before and after the exercise, subjects were asked to rate their pain using a visual analogic scale. FINDINGS: Significant between-group differences in pain at both baseline and following exercise were found (both, P < 0.007). In healthy controls, pain was significantly improved following exercise (P = 0.002). No change in oxidative stress level after exercise was found. Significant correlation between TBARS levels and pain was found at baseline (r = 0.540; P = 0.021) and after exercise (r = 0.524; P = 0.024) in patients only. No significant correlation between TBARS and heart rate variability at baseline or following exercise was found in either group. However, a significant correlation was found between exercise-induced changes in HRV and TBARS in healthy controls (r = -0.720; P = 0.001). IMPLICATIONS: Oxidative stress showed an association with pain symptoms in people with ME/CFS, but no exercise-induced changes in oxidative stress were found. In addition, the change in parasympathetic activity following exercise partially accounted for the change in oxidative stress in healthy controls. More research is required to further explore this link.

Explaining pain following cancer: a practical guide for clinicians.

BACKGROUND: Pain is one of the most prevalent and debilitating symptom following cancer treatment. OBJECTIVES: This paper entails a practical guide for clinicians willing to apply pain neuroscience education (PNE) in this specific population, or clinical researchers willing to examine the effects of PNE in patients suffering from pain following cancer. RESULTS: Patient-specific information (i.e. beliefs, cognitions, pain memories, social factors) as well as identification of the dominant pain mechanism are needed to tailor the education to the specific needs and beliefs of the patient. Therapists require an in-depth understanding of pain mechanisms, the skills to explain to their patients various pain mechanisms, specific communication skills (e.g. Socratic-style dialogof education) and experience with current evidence-based biopsychosocially-driven pain management strategies for successful implementation of PNE in the clinic. Rather than purely focusing on the biomedical characteristics of pain following cancer (e.g., tissue damage due to past cancer treatment), PNE implies teaching patients about the underlying biopsychosocial mechanisms of pain. Its application is backed-up by mounting evidence supporting the effectiveness of PNE in non-cancer pain populations, and a pilot study in patients having pain following cancer. CONCLUSION: PNE is a potential solution to improve pain outcome in cancer survivors. Further research using sufficiently powered and well-designed randomized clinical trials should be conducted to examine the potential of PNE in patients having pain following cancer.