Pain Science in Practice (Part 7): How Is Descending Modulation of Pain Measured?

SYNOPSIS: Understanding the descending pain modulatory system allows for a neuroscientific explanation of naturally occurring pain relief. Evidence from basic science and clinical studies on the effectiveness of drugs in certain patient groups led to pharmacological manipulation of the descending pain modulatory system for analgesia. Understanding mechanisms and theories helps clinicians make sense of chronic musculoskeletal pain. This editorial explains how test paradigms, including conditioned pain modulation, offset analgesia, and stress-induced analgesia work, provide an overview of a placebo analgesia circuitry, and discusses how evoking activity in the descending pain modulatory system using specific paradigms can give new insights into how specific treatments work to reduce pain. J Orthop Sports Phys Ther 2024;54(2):1-6. doi:10.2519/jospt.2024.12113.

Pain Science in Practice (Part 6): How Does Descending Modulation of Pain Work?

SYNOPSIS: To understand the neuroscience of pain relief, one must know about the descending pain modulatory system. Neuronal pathways that originate in the brainstem and project to the spinal cord to modulate spinal neuronal activity provide a well-documented perspective on the mechanisms of analgesia that underpin pharmacological and nonpharmacological treatment options for people with musculoskeletal pain. Peripheral stimuli or signals from the cortex and subcortical regions of the brain can trigger the descending pain modulatory system (DPMS). The system helps explain how counter-stimulation techniques (eg, acupuncture and manual therapy), the patients' expectations and beliefs, and social or contextual factors could influence how people experience pain. J Orthop Sports Phys Ther 2024;54(2):1-4. doi:10.2519/jospt.2024.12112.

Self-reported characteristics of people seeking primary care physiotherapy in Denmark: A cross-sectional study.

BACKGROUND: Limited knowledge exists on the self-reported characteristics of patients seeking primary care physiotherapy in Denmark. OBJECTIVES: To describe primary symptom site, co-occurrent pain sites, pain intensity, symptom duration, and number of symptom episodes in patients seeking primary care physiotherapy using patient-reported data. METHODS: Cross-sectional study of patients seeking primary care physiotherapy within a nationwide network of clinics in Denmark (FysioDanmark® ). Data from the FysioDanmark® clinical database with patient-reported information obtained from questionnaires distributed to patients prior to their first consultation were used. This included primary symptom site, co-occurrent pain sites, pain intensity (0-10 numeric rating scale), symptom duration, and number of symptom episodes. RESULTS: Data from 61,097 patients (57% female) aged 42 years (interquartile range 29-53) and 63,566 first visits were included. The most common reasons for seeking care were back- (22.9%), non-specific- (19.8%) and shoulder symptoms (15.9%). The majority of patients (89.4%) reported symptoms lasting longer than 7 days, and many experienced recurrent episodes. Median pain intensity ranged from 3 to 5 across primary symptom sites and age groups. In general, females reported higher pain intensity than males. CONCLUSION: Danish patients seeking primary care physiotherapy most commonly presented with back, non-specific, and shoulder symptoms, with mild-to-moderate pain lasting longer than 7 days, and many with recurrent episodes.

Musculoskeletal Pain: Current and Future Directions of Physical Therapy Practice.

Musculoskeletal (MSK) pain is 1 of the most common problems managed by clinicians in MSK care. This article reviews current frameworks for the assessment and management of MSK pain within evidence-based physical therapy practice. Key considerations related to the biopsychosocial model of pain, evidence-based practice, assessment, treatment, physical activity/movement behavior, risk stratification, communication as well as patient education and self-management skills within physical therapy and physical and rehabilitation medicine are addressed. The future direction of MSK pain management is also discussed, including strategies to promote evidence-based practice, behavior change, social prescribing, and the use of technologies.

Pain Science in Practice (Part 5): Central Sensitization II.

SYNOPSIS: Central sensitization is an umbrella-term for facilitated synaptic plasticity. This editorial explains wind-up, classical central sensitization, and long-term potentiation. Wind-up and LTP are generally considered homosynaptic, while classical central sensitization is classified as heterosynaptic. Wind-up is very short lived and unlikely to play a significant role in chronic musculoskeletal pain, however, both LTP and classical central sensitization could potentially be involved in chronic pain. J Orthop Sports Phys Ther 2023;53(2):55-58. doi:10.2519/jospt.2023.11571.

Pain Science in Practice (Part 4): Central Sensitization I.

SYNOPSIS: Central sensitization is an umbrella term for facilitated synaptic plasticity. This editorial (1) explains the differences between homosynaptic and heterosynaptic plasticity, (2) explains the role of glia cells in dorsal horn neuroplasticity, and (3) briefly discusses the clinical relevance of central sensitization and nociplastic pain. Part 5 covers wind-up, classical central sensitization, and long-term potentiation. J Orthop Sports Phys Ther 2023;53(1):1-4. doi:10.2519/jospt.2023.11569.

What is known and what is still unknown within chronic musculoskeletal pain? A systematic evidence and gap map.

ABSTRACT: Evidence and gap maps (EGMs) can be used to identify gaps within specific research areas and help guide future research agendas and directions. Currently, there are no EGMs within the broad domain of chronic musculoskeletal (MSK) pain in adults. The aim of this study was to create a contemporary EGM of interventions and outcomes used for research investigating chronic MSK pain. This EGM was based on systematic reviews of interventions published in scientific journals within the past 20 years. Embase, PubMed, the Cochrane Library, and PsycINFO were used to retrieve studies for inclusion. The quality of the included reviews was assessed using AMSTAR-II. Interventions were categorised as either physical, psychological, pharmacological, education/advice, interdisciplinary, or others. Outcomes were categorised using the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations. Of 4299 systematic reviews, 457 were included. Of these, 50% were rated critically low quality, 25% low quality, 10% moderate quality, and 15% rated high quality. Physical interventions (eg, exercise therapy) and education were the most common interventions reported in 80% and 20% of the studies, respectively. Pain (97%) and physical functioning (87%) were the most reported outcomes in the systematic reviews. Few systematic reviews used interdisciplinary interventions (3%) and economic-related outcomes (2%). This contemporary EGM revealed a low proportion of high-quality evidence within chronic MSK pain. This EGM clearly outlines the lack of high-quality research and the need for increased focus on interventions encompassing the entire biopsychosocial perspective.

Participatory research: a Priority Setting Partnership for chronic musculoskeletal pain in Denmark.

OBJECTIVES: Patient and stakeholder engagements in research have increasingly gained attention in healthcare and healthcare-related research. A common and rigorous approach to establish research priorities based on input from people and stakeholders is the James Lind Alliance Priority Setting Partnership (JLA-PSP). The aim of this study was to establish research priorities for chronic musculoskeletal (MSK) pain by engaging with people living with chronic MSK pain, relatives to people living with chronic MSK pain, healthcare professionals (HCP), and researchers working with chronic MSK pain. METHODS: This JLA-PSP included a nation-wide survey in Denmark, an interim prioritisation, and an online consensus building workshop. The information gained from this was the basis for developing the final list of specific research priorities within chronic MSK pain. RESULTS: In the initial survey, 1010 respondents (91% people living with chronic MSK pain/relatives, 9% HCPs/researchers) submitted 3121 potential questions. These were summarised into 19 main themes and 36 sub-themes. In the interim prioritisation exercise, 51% people living with pain/relatives and 49% HCPs/researchers reduced the list to 33 research questions prior to the final priority setting workshop. 23 participants attended the online workshop (12 people/relatives, 10 HCPs, and 1 researcher) who reached consensus for the most important research priorities after two rounds of discussion of each question. CONCLUSIONS: This study identified several specific research questions generated by people living with chronic MSK pain, relatives, HCPs, and researchers. The stakeholders proposed prioritization of the healthcare system's ability to support patients, focus on developing coherent pathways between sectors and education for both patients and HCP. These research questions can form the basis for future studies, funders, and be used to align research with end-users' priorities.

Pain Science in Practice (Part 3): Peripheral Sensitization.

SYNOPSIS: In most cases, tissue injuries lead to inflammation and sensitization. From a neuroscience perspective, this is why one usually hurts when one is injured. Peripheral sensitization is an essential principle in pain science, and it is associated with hyperalgesia, inflammation, and clinical pain conditions, including acute injuries and rheumatological diseases. This editorial explains peripheral sensitization, neurogenic inflammation, and the axon reflex, as well as the role of second messengers and peptidergic C-fibers. J Orthop Sports Phys Ther 2022;52(6):303-306. doi:10.2519/jospt.2022.11202.

Pain Science in Practice: What Is Pain Neuroscience? Part 1.

SYNOPSIS: This first article in the JOSPT "Pain Science in Practice" series explains fundamental concepts related to neuroscience: transduction, transmission, modulation, and perception. J Orthop Sports Phys Ther 2022;52(4):163-165. doi:10.2519/jospt.2022.10995.

Pain Science in Practice: What Is Pain Neuroscience? Part 2.

SYNOPSIS: Biomechanical explanations for musculoskeletal pain are abundant and have been used for many years; however, researchers and clinicians are moving toward neuroscience-based explanations to study and explain them. This article discusses some specific mechanisms, commonly used in pain medicine, and their somewhat less specific but equally important role in nonpharmacological management of musculoskeletal pain. The article also explains the role of different receptors and how they relate to clinical conditions. J Orthop Sports Phys Ther 2022;52(4):166-168. doi:10.2519/jospt.2022.10994.

Pain Science in Practice: Linking Basic Pain Science to the Clinic and Quality Musculoskeletal Rehabilitation Care.

SYNOPSIS: To understand pain, professionals need a basic understanding of neuroscience. The "pain science in practice" series is aimed at clinicians and explains key elements of pain-related sciences and the role they play in clinical practice, from clinical reasoning to management. J Orthop Sports Phys Ther 2022;52(3):125-126. doi:10.2519/jospt.2022.10992.

Reducing the Weight of Spinal Pain in Children and Adolescents.

Spinal pain in adults is a significant burden, from an individual and societal perspective. According to epidemiologic data, spinal pain is commonly found in children and adolescents, where evidence emerging over the past decade has demonstrated that spinal pain in adults can, in many cases, be traced back to childhood or adolescence. Nevertheless, very little focus has been on how to best manage spinal pain in younger age groups. The purpose of this article is to put the focus on spinal pain in children and adolescents and highlight how and where these problems emerge and how they are commonly dealt with. We will draw on findings from the relevant literature from adults to highlight potential common pathways that can be used in the management of spinal pain in children and adolescents. The overall focus is on how healthcare professionals can best support children and adolescents and their caregivers in making sense of spinal pain (when present) and support them in the self-management of the condition.

Nonpharmacological Treatment of Persistent Postconcussion Symptoms in Adults: A Systematic Review and Meta-analysis and Guideline Recommendation.

Importance: Persistent (>4 weeks) postconcussion symptoms (PPCS) are challenging for both patients and clinicians. There is uncertainty about the effect of commonly applied nonpharmacological treatments for the management of PPCS. Objective: To systematically assess and summarize evidence for outcomes related to 7 nonpharmacological interventions for PPCS in adults (aged >18 years) and provide recommendations for clinical practice. Data Sources: Systematic literature searches were performed via Embase, MEDLINE, PsycINFO, CINAHL, PEDro, OTseeker, and Cochrane Reviews (via MEDLINE and Embase) from earliest possible publication year to March 3, 2020. The literature was searched for prior systematic reviews and primary studies. To be included, studies had to be intervention studies with a control group and focus on PPCS. Study Selection: A multidisciplinary guideline panel selected interventions based on frequency of use and need for decision support among clinicians, including early information and advice, graded physical exercise, vestibular rehabilitation, manual treatment of neck and back, oculomotor vision treatment, psychological treatment, and interdisciplinary coordinated rehabilitative treatment. To be included, studies had to be intervention studies within the areas of the predefined clinical questions, include a control group, and focus on symptoms after concussion or mild traumatic brain injury. Data Extraction and Synthesis: Extraction was performed independently by multiple observers. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data abstraction and data quality assessment. Included studies were assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the Cochrane Risk of Bias (randomized clinical trials) tool. Meta-analysis was performed for all interventions where possible. Random-effects models were used to calculate pooled estimates of effects. The level and certainty of evidence was rated and recommendations formulated according to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Main Outcomes and Measures: All outcomes were planned before data collection began according to a specified protocol. The primary outcomes were the collective burden of PPCS and another outcome reflecting the focus of a particular intervention (eg, physical functioning after graded exercise intervention). Results: Eleven systematic reviews were identified but did not contribute any primary studies; 19 randomized clinical trials comprising 2007 participants (1064 women [53.0%]) were separately identified and included. Evidence for the 7 interventions ranged from no evidence meeting the inclusion criteria to very low and low levels of evidence. Recommendations were weak for early information and advice, graded physical exercise, vestibular rehabilitation, manual treatment of the neck and back, psychological treatment, and interdisciplinary coordinated rehabilitative treatment. No relevant evidence was identified for oculomotor vision treatment, so the panel provided a good clinical practice recommendation based on consensus. Conclusions and Relevance: Based on very low to low certainty of evidence or based on consensus, the guideline panel found weak scientific support for commonly applied nonpharmacological interventions to treat PPCS. Results align with recommendations in international guidelines. Intensified research into all types of intervention for PPCS is needed.

European knowledge alliance for innovative measures in prevention of work-related musculoskeletal pain disorders (Prevent4Work Project): protocol for an international mixed-methods longitudinal study.

INTRODUCTION: Work-related musculoskeletal (MSK) pain is a highly prevalent condition and one of the main contributors to disability and loss of work capacity. Current approaches to the management and prevention of work-related MSK pain do not consistently integrate current evidence-based knowledge and seem to be outdated. The Prevent4Work (P4W) Project aims to collect and spread evidence-based information to improve the management and prevention of work-related MSK pain. P4W will longitudinally investigate (1) risk factors associated with the prevalence of work-related MSK pain, (2) predictive factors for new events of work-related MSK pain in the short term and (3) the modification of pain beliefs after participating in evidence-based e-learning courses. METHODS AND ANALYSIS: This project employs a mixed-methods design with international cohorts of workers from Spain, Italy and Denmark. All participants will be assessed using self-reported variables at baseline (ie, cross-sectional design) with follow-up after 3 and 6 months (ie, prospective-predictive design). Throughout the first phase (0-3 months), all participants will be offered to self-enrol in e-learning courses on work-related MSK pain. Changes in pain beliefs (if any) will be assessed. The dataset will include sociodemographic characteristics, physical and psychological job demands, lifestyle-related factors, MSK pain history and pain beliefs. At baseline, all participants will additionally complete the P4W questionnaire developed to detect populations at high risk of suffering work-related MSK pain.Descriptive statistics, binary logistic regression, and analysis of variance will be used to identify the significant factors that influence the history of work-related MSK pain, evaluate the short-term prediction capacity of the P4W questionnaire, and investigate whether workers' participation in e-learning courses will modify their pain beliefs. ETHICS AND DISSEMINATION: The study received ethical approval from the Ethical Committee of San Jorge University (USJ011-19/20). The results will be made available via peer-reviewed publications, international conferences and P4W official channels.

Supervised Training Compared With No Training or Self-training in Patients With Subacromial Pain Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: To study the effects of supervised training in adults with subacromial pain syndrome. DATA SOURCES: Embase, MEDLINE, Cochrane Library, Cumulative Index to Nursing and Allied Health, and Physiotherapy Evidence Database were searched from inception to March 2020. STUDY SELECTION: Independent reviewers selected randomized controlled trials comparing supervised training with (1) no training or (2) self-training in adults with subacromial pain syndrome lasting for at least 1 month. Critical outcomes were shoulder pain, function, and patient-perceived effect. Important outcomes included other potential benefits and adverse events at 3-month follow-up. DATA EXTRACTION: Two independent reviewers extracted data for the meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias tool 1, and certainty of evidence was evaluated using the Grades of Recommendation Assessment, Development, and Evaluation (GRADE). DATA SYNTHESIS: Ten studies (n=597, 43% female) were included. Supervised training resulted in larger improvements than no training on pain (at rest: n=286; mean difference [MD], 1.68; 95% confidence interval [CI], 0.31-3.06 on 0-10 scale; during movement: n=353; MD, 1.84; 95% CI,0.91-2.76), function (n=396; standardized MD, 0.30; 95% CI, 0.07-0.52), and patient-perceived effect (n=118; risk ratio, 1.43; 95% CI, 0.87-2.34). Supervised training had potential benefits regarding quality of life, return to work, dropout, and training adherence, albeit more patients reported mild, transient pain after training. Supervised training and self-training showed equal improvements on pain (n=44) and function (n=76), with no data describing patient-perceived effect. Certainty of evidence was low for critical outcomes and low-moderate for other outcomes. CONCLUSIONS: Supervised training might be superior to no training and equally effective as self-training on critical and important outcomes. Based on low-moderate certainty of evidence, these findings support a weak recommendation for supervised training in adults with subacromial pain syndrome.

The Effect of Stress on Repeated Painful Stimuli with and Without Painful Conditioning.

OBJECTIVES: Stress and pain have been interrelated in clinical widespread pain conditions. Studies indicate that acute experimental stress in healthy volunteers has a negative effect on the descending inhibitory pain control system and thus the ability to inhibit one painful stimulus with another (conditioned pain modulation [CPM]) although without effect on general pain sensitivity. CPM effects can be assessed immediately after the stress induction, whereas some physiological stress responses (e.g., cortisol release) are delayed and longer lasting. It is unclear whether CPM may relate to stress-induced increases in cortisol. DESIGN: Twenty-five healthy men had CPM effects measured over a period of 10 minutes. Pain detection thresholds (PDTs) were assessed by repeated test stimuli with cuff algometry on one leg, with and without painful cuff pressure conditioning on the contralateral leg. CPM effects, assessed as the increase in PDT during conditioning stimulation compared with without, were measured before and after experimental stress and a control condition (Montreal Imaging Stress Task [MIST]). Saliva cortisol levels and self-perceived stress were collected. RESULTS: Participants reported the MIST to be more stressful compared with the MIST control, but cortisol levels did not change significantly from baseline. In all sessions, PDT increased during conditioning (P = 0.001), although the MIST compared with the MIST control had no significant effect on PDT or CPM effects. A negative correlation between changes in cortisol and conditioned PDT was found when applying the MIST (P < 0.03). CONCLUSIONS: No significant effect of stress was found on CPM compared with a matched control condition. Individual changes in experimental stress and in conditioned pain sensitivity may be linked with cortisol.

Delayed effects of attention on pain sensitivity and conditioned pain modulation.

BACKGROUND: Efficacy of pain modulation is assessed as the difference in pain sensitivity during a painful conditioning, compared to before (conditioning pain modulation, CPM). Attention can be assessed with the Stroop task, in which participants report the number of words on a screen; either congruent or incongruent with the value of the words. Attention away from painful stimuli during CPM enhances the CPM effect. However, it is unknown if attention influences CPM effects when the two are done in sequence. METHODS: Healthy men (n = 25) underwent cuff algometry CPM-assessment where the pressure-pain detection and tolerance thresholds (PTT) were recorded on one leg with and without contralateral conditioning. Two identical sessions of four test stimuli equal to PTT (5 s, 1-min interval, scored on a visual analogue scale, VAS) with a painful conditioning from the second to the last test-stimulus were performed. Stroop sessions were followed by test stimuli with or without painful conditioning. RESULTS: The VAS scores in the first two sessions showed excellent reliability (ICC = 0.92). VAS scores were lower in sessions with Stroop compared to sessions without Stroop (p = .05) indicating an analgesic effect of Stroop. Participants were subgrouped into CPM responders and CPM non-responders according to CPM effects in the first two sessions. CPM non-responders (n = 13) showed facilitation to repeated noxious stimuli in all sessions with no effect of conditioning or Stroop (p = .02). CONCLUSION: Attention and CPM both modulate pain in healthy men. Attention-induced analgesia works in CPM non-responders. Results indicate that attention and CPM are not the same and that they do not demonstrate additive effects when applied in sequence. SIGNIFICANCE: Pain sensitivity is reduced after an attention task in healthy men. The delayed effects from attention only have minor effects on Conditioned Pain Modulation (CPM), and results support that attention-driven analgesia works independently of CPM. Results indicate that individual strategies for pain inhibition exist and that an overlap between the mechanisms of CPM and selective attention is limited. Moreover, painful phasic stimuli may increase the number of healthy volunteers with negative CPM effects.