Placebo effects in low back pain; a systematic review and meta‐analysis of the literature

Abstract

Background and Objective

The current treatments of primary musculoskeletal low back pain (LBP) have a low to moderate efficacy, which might be improved by looking at the contribution of placebo effects. However, the size of true placebo effects in LBP is unknown. Therefore, a systematic review and meta-analysis were executed of randomized controlled trials investigating placebo effects in LBP.

Databases and Data treatment

The study protocol was registered in the international prospective register of systematic reviews Prospero (CRD42019148745). A literature search (in PubMed, Embase, The Cochrane Library, CINAHL and PsycINFO) up to 2021 February 16^th yielded 2423 studies. Two independent reviewers assessed eligibility and risk of bias.

Results

Eighteen studies were eligible for the systematic review and 5 for the meta-analysis. Fourteen of the 18 studies were clinical treatment studies, and 4 were experimental studies specifically assessing placebo effects. The clinical treatment studies provided varying evidence for placebo effects in chronic LBP, but insufficient evidence for acute and subacute LBP. Most experimental studies investigating chronic LBP revealed significant placebo effects. The meta-analysis of 5 treatment studies investigating chronic LBP depicted a significant moderate effect size of placebo for pain intensity (SMD = 0.57) and disability (SMD = 0.52).

Conclusions

This review shows a significant contribution of placebo effects to chronic LBP symptom relief in clinical and experimental conditions. The meta-analysis revealed that placebo effects can influence chronic LBP intensity and disability. However, additional studies are required for more supporting evidence and evidence for placebo effects in acute or subacute LBP.

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During Capsaicin‐induced Central Sensitization Brush Allodynia is Associated with Baseline Warmth Sensitivity, Whereas Mechanical Hyperalgesia is Associated with Painful Mechanical Sensibility, Anxiety and Somatization

Abstract

Background

Mechanical hyperalgesia and allodynia incidence varies considerably among neuropathic pain patients. This study explored whether sensory or psychological factors associate with mechanical hyperalgesia and brush allodynia in a human experimental model.

Methods

Sixty-six healthy volunteers (29 male) completed psychological questionnaires and participated in two quantitative sensory testing (QST) sessions. Warmth detection threshold (WDT), heat pain threshold (HPT) and suprathreshold mechanical pain (STMP) ratings were measured before exposure to a capsaicin-heat pain model (C-HP). After C-HP exposure, brush allodynia and STMP were measured in one session, while mechanical hyperalgesia was measured in another session.

Results

WDT and HPT measured in sessions separated by one month demonstrated significant, but moderate levels of reliability (WDT: ICC=0.5, 95%CI[0.28,0.77]; HPT: ICC=0.62, 95%CI[0.40,0.77]). Brush allodynia associated with lower WDT (z=-3.06, p=0.002; ϕ=0.27). Those with allodynia showed greater hyperalgesia intensity (F=7.044, p=0.010, η_p ²=0.107) and area (F=9.319, p=0.004, η_p ²=0.163) than those without allodynia. No psychological self-report measures were significantly different between allodynic and non-allodynic groups. Intensity of hyperalgesia in response to lighter mechanical stimuli was associated with lower HPT, higher STMP ratings, and higher Pain Sensitivity Questionnaire scores at baseline. Hyperalgesia to heavier probe stimuli associated with state anxiety and to a lesser extent somatic awareness. Hyperalgesic area associated with lower baseline HPT and higher STMP ratings. Hyperalgesic area was not correlated with allodynic area across individuals.

Conclusions

These findings support research in neuropathic pain patients and human experimental models that peripheral sensory input and individual sensibility are related to development of mechanical allodynia and hyperalgesia during central sensitization, while psychological factors play a lesser role.

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Placebo effects in low back pain; a systematic review and meta‐analysis of the literature

Abstract

Background and Objective

The current treatments of primary musculoskeletal low back pain (LBP) have a low to moderate efficacy, which might be improved by looking at the contribution of placebo effects. However, the size of true placebo effects in LBP is unknown. Therefore, a systematic review and meta-analysis were executed of randomized controlled trials investigating placebo effects in LBP.

Databases and Data treatment

The study protocol was registered in the international prospective register of systematic reviews Prospero (CRD42019148745). A literature search (in PubMed, Embase, The Cochrane Library, CINAHL and PsycINFO) up to 2021 February 16^th yielded 2423 studies. Two independent reviewers assessed eligibility and risk of bias.

Results

Eighteen studies were eligible for the systematic review and 5 for the meta-analysis. Fourteen of the 18 studies were clinical treatment studies, and 4 were experimental studies specifically assessing placebo effects. The clinical treatment studies provided varying evidence for placebo effects in chronic LBP, but insufficient evidence for acute and subacute LBP. Most experimental studies investigating chronic LBP revealed significant placebo effects. The meta-analysis of 5 treatment studies investigating chronic LBP depicted a significant moderate effect size of placebo for pain intensity (SMD = 0.57) and disability (SMD = 0.52).

Conclusions

This review shows a significant contribution of placebo effects to chronic LBP symptom relief in clinical and experimental conditions. The meta-analysis revealed that placebo effects can influence chronic LBP intensity and disability. However, additional studies are required for more supporting evidence and evidence for placebo effects in acute or subacute LBP.

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During Capsaicin‐induced Central Sensitization Brush Allodynia is Associated with Baseline Warmth Sensitivity, Whereas Mechanical Hyperalgesia is Associated with Painful Mechanical Sensibility, Anxiety and Somatization

Abstract

Background

Mechanical hyperalgesia and allodynia incidence varies considerably among neuropathic pain patients. This study explored whether sensory or psychological factors associate with mechanical hyperalgesia and brush allodynia in a human experimental model.

Methods

Sixty-six healthy volunteers (29 male) completed psychological questionnaires and participated in two quantitative sensory testing (QST) sessions. Warmth detection threshold (WDT), heat pain threshold (HPT) and suprathreshold mechanical pain (STMP) ratings were measured before exposure to a capsaicin-heat pain model (C-HP). After C-HP exposure, brush allodynia and STMP were measured in one session, while mechanical hyperalgesia was measured in another session.

Results

WDT and HPT measured in sessions separated by one month demonstrated significant, but moderate levels of reliability (WDT: ICC=0.5, 95%CI[0.28,0.77]; HPT: ICC=0.62, 95%CI[0.40,0.77]). Brush allodynia associated with lower WDT (z=-3.06, p=0.002; ϕ=0.27). Those with allodynia showed greater hyperalgesia intensity (F=7.044, p=0.010, η_p ²=0.107) and area (F=9.319, p=0.004, η_p ²=0.163) than those without allodynia. No psychological self-report measures were significantly different between allodynic and non-allodynic groups. Intensity of hyperalgesia in response to lighter mechanical stimuli was associated with lower HPT, higher STMP ratings, and higher Pain Sensitivity Questionnaire scores at baseline. Hyperalgesia to heavier probe stimuli associated with state anxiety and to a lesser extent somatic awareness. Hyperalgesic area associated with lower baseline HPT and higher STMP ratings. Hyperalgesic area was not correlated with allodynic area across individuals.

Conclusions

These findings support research in neuropathic pain patients and human experimental models that peripheral sensory input and individual sensibility are related to development of mechanical allodynia and hyperalgesia during central sensitization, while psychological factors play a lesser role.

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Illness perceptions and illness behaviours in back pain: A cross‐sectional cluster analysis

Abstract

Background

Individuals’ perceptions of back pain may shape what they do in response to manage their pain – for example, self-care, medication, seeking healthcare. Illness perceptions encompass a variety of beliefs such as how long pain is expected to last and whether treatments are perceived to control pain. Whether these beliefs meaningfully cluster, and whether these clusters are associated with how people manage their back pain is currently unknown.

Methods

1343 individuals with back pain from a general population sample completed the brief Illness Perceptions Questionnaire and measures about their pain and illness behaviours. Using a two-stage cluster analysis, we identified four distinct clusters of individuals. Logistic regression was used to investigate relationships between cluster membership and illness behaviours.

Results

After adjustment for sociodemographic characteristics, pain severity, interference and duration, relative to a Low Threat illness perception cluster, a High Threat cluster was more likely to have contacted a GP (OR 3.03, 95% CI: 1.75-5.23) and a Moderate Threat-High Treatment Control cluster was more likely to have consulted a physical therapist (OR 2.21, 95% CI: 1.26-3.87). Both the Moderate Threat-High Treatment Control cluster and High Threat cluster were also less likely to have reported self-care (OR 0.64, 95% CI: 0.43-0.95; OR 0.53, 95% CI: 0.34-0.83, respectively).

Conclusions

The cluster analysis provided a meaningful classification of individuals based on their cognitive illness perceptions of their back pain, as these clusters were associated with different illness behaviours. Interventions which modify clusters of illness perceptions may be effective in influencing how individuals respond to back pain.

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The mediating effect of pain catastrophizing on pain intensity: the influence of the timing of assessments

Abstract

Background

Pain catastrophizing underpins several psychosocial theories of pain, but there is limited evidence to support the proposal that changes in pain catastrophizing cause changes in pain. Results from mediation analyses have conflicting results, and one reason for these might be the timing of the assessment of pain catastrophizing. This study aimed to test the effect of the timing of pain catastrophizing on pain intensity.

Methods

Causal mediation analysis using data from a randomized controlled trial which included 100 participants with chronic low back pain. The trial found that clinical hypnosis, compared to pain education, reduced worst pain intensity and pain catastrophizing. In model 1, we used data from 2-week follow-up for pain catastrophizing and 3-month follow-up for pain. In model 2, we used data from 3-month follow-up for both pain catastrophizing and pain.

Results

The intervention had a significant average total effect on pain (-1.34 points, 95% CI -2.50 to -0.13). The average causal mediation effect was significant when pain catastrophizing and pain were measured at the same time (-0.62 points, 95% CI -1.30 to -0.11), but not significant when pain catastrophizing and pain intensity were measured at different times (-0.10 points, 95% CI -0.42 to 0.09).

Conclusions

The timing of the assessment influenced the mediating role of pain catastrophizing on pain intensity. These results raise questions on the casual role that pain catastrophizing has on pain intensity. Psychosocial interventions such as clinical hypnosis can reduce pain intensity even when there has been no change in pain catastrophizing.

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Identifying goals in patients with chronic pain: a European survey

Abstract

Background

Chronic pain is a major healthcare issue that often requires an interdisciplinary treatment approach. Defining relevant treatment goals is one of the crucial steps in creating successful rehabilitation schemes. Therefore, the first aim is to explore goals that patients suffering from chronic pain aim to achieve. The second aim is to translate those goals into measurable functional outcome variables which can be used to measure treatment success.

Methods

An online survey was developed and spread through local pain alliances in six European countries. Participants, patients suffering from chronic pain, were asked to report their most important goals, combined with a rank to denote the importance of each goal. For the highest ranked goals, participants were asked to decompose their goal into functional postures and the number of minutes per posture to achieve this goal.

Results

We approached 1494 persons, of which 487 effectively completed this survey. The highest ranked goals were taking part in family and social activities (72.55%), pain reduction (91.18%) and household tasks (68.14%). Obtaining pain reduction was most often ranked first (55.75%), followed by improving sleep (12.25%) and taking part in family or social activities (11.00%). For all goals, walking was a crucial component.

Conclusions

Goals of chronic pain patients are in line with previously explored expectations, denoting the importance of achieving pain relief combined with improvements on the level of activities and participation. This survey indicates that rehabilitation programs should definitely focus on improving walking ability, due to its importance in underpinning overall goal achievement.

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[Editorial] Rethinking chronic pain

To live with chronic pain is to live with daily challenges around simple tasks that others take for granted. It often means being disbelieved, stigmatised for not getting better, or judged as not coping. It might mean living with poor mental health and self-esteem, absenteeism from school or work, the breakdown of relationships, and socioeconomic disadvantage. For society, the costs are staggering: low back pain is the leading cause of years lost to disability and chronic pain costs billions of dollars through health system expenditures, productivity losses, reduced quality of life, and informal care.

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[Comment] Pragmatic but flawed: the NICE guideline on chronic pain

The 2021 UK National Institute for Health and Care Excellence (NICE) guidance on chronic pain1 (chronic primary pain, chronic secondary pain, or both) and the management of chronic primary pain among people older than 16 years has prompted debate among clinicians. The NICE recommendations on assessment of chronic pain, with person-centred assessment at its heart, make good sense and are to be welcomed. But the recommendations on chronic primary pain are more controversial.

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[Series] Chronic pain: an update on burden, best practices, and new advances

Chronic pain exerts an enormous personal and economic burden, affecting more than 30% of people worldwide according to some studies. Unlike acute pain, which carries survival value, chronic pain might be best considered to be a disease, with treatment (eg, to be active despite the pain) and psychological (eg, pain acceptance and optimism as goals) implications. Pain can be categorised as nociceptive (from tissue injury), neuropathic (from nerve injury), or nociplastic (from a sensitised nervous system), all of which affect work-up and treatment decisions at every level; however, in practice there is considerable overlap in the different types of pain mechanisms within and between patients, so many experts consider pain classification as a continuum.

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[Series] Nociplastic pain: towards an understanding of prevalent pain conditions

Nociplastic pain is the semantic term suggested by the international community of pain researchers to describe a third category of pain that is mechanistically distinct from nociceptive pain, which is caused by ongoing inflammation and damage of tissues, and neuropathic pain, which is caused by nerve damage. The mechanisms that underlie this type of pain are not entirely understood, but it is thought that augmented CNS pain and sensory processing and altered pain modulation play prominent roles.

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[Series] Neuromodulation for chronic pain

Neuromodulation is an expanding area of pain medicine that incorporates an array of non-invasive, minimally invasive, and surgical electrical therapies. In this Series paper, we focus on spinal cord stimulation (SCS) therapies discussed within the framework of other invasive, minimally invasive, and non-invasive neuromodulation therapies. These therapies include deep brain and motor cortex stimulation, peripheral nerve stimulation, and the non-invasive treatments of repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation.

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Comment on "Analgesic effect of music during wound care among patients with diaphyseal tibial fractures: Randomized controlled trial"

Abstract

With great interest, we read the article by Ferraz et al published in 2021 in the Eur J Pain (Ferraz et al., 2021). The authors performed a randomized controlled trial (RCT) and concluded that “Listening to music is effective for relieving acute procedural pain during the first post-operative tibial fracture dressing change. Music should be incorporated into the multimodal analgesia protocols for management of orthopedic postoperative wound care related pain.” At the outset, we would like to congratulate the authors for writing an informative article with novelty. Nevertheless, we have several suggestions and queries that we would like to communicate with the authors.

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Comment on "Analgesic effect of music during wound care among patients with diaphyseal tibial fractures: Randomized controlled trial"

Abstract

With great interest, we read the article by Ferraz et al published in 2021 in the Eur J Pain (Ferraz et al., 2021). The authors performed a randomized controlled trial (RCT) and concluded that “Listening to music is effective for relieving acute procedural pain during the first post-operative tibial fracture dressing change. Music should be incorporated into the multimodal analgesia protocols for management of orthopedic postoperative wound care related pain.” At the outset, we would like to congratulate the authors for writing an informative article with novelty. Nevertheless, we have several suggestions and queries that we would like to communicate with the authors.

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Pain Intensity and Pain Interference in People with Progressive Multiple Sclerosis Compared to People with Relapsing-Remitting Multiple Sclerosis

Publication date: Available online 25 May 2021

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Lindsey M. Knowles, Kala M. Phillips, Tracy E. Herring, Kevin N. Alschuler, Mark P. Jensen, Aaron P. Turner, Dawn M. Ehde

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Pain Intensity and Pain Interference in People with Progressive Multiple Sclerosis Compared to People with Relapsing-Remitting Multiple Sclerosis

Publication date: Available online 25 May 2021

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Lindsey M. Knowles, Kala M. Phillips, Tracy E. Herring, Kevin N. Alschuler, Mark P. Jensen, Aaron P. Turner, Dawn M. Ehde

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Pain Intensity and Pain Interference in People with Progressive Multiple Sclerosis Compared to People with Relapsing-Remitting Multiple Sclerosis

Publication date: Available online 25 May 2021

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Lindsey M. Knowles, Kala M. Phillips, Tracy E. Herring, Kevin N. Alschuler, Mark P. Jensen, Aaron P. Turner, Dawn M. Ehde

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Pain Intensity and Pain Interference in People with Progressive Multiple Sclerosis Compared to People with Relapsing-Remitting Multiple Sclerosis

Publication date: Available online 25 May 2021

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Lindsey M. Knowles, Kala M. Phillips, Tracy E. Herring, Kevin N. Alschuler, Mark P. Jensen, Aaron P. Turner, Dawn M. Ehde

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Pain Intensity and Pain Interference in People with Progressive Multiple Sclerosis Compared to People with Relapsing-Remitting Multiple Sclerosis

Publication date: Available online 25 May 2021

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Lindsey M. Knowles, Kala M. Phillips, Tracy E. Herring, Kevin N. Alschuler, Mark P. Jensen, Aaron P. Turner, Dawn M. Ehde

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Pain Intensity and Pain Interference in People with Progressive Multiple Sclerosis Compared to People with Relapsing-Remitting Multiple Sclerosis

Publication date: Available online 25 May 2021

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Lindsey M. Knowles, Kala M. Phillips, Tracy E. Herring, Kevin N. Alschuler, Mark P. Jensen, Aaron P. Turner, Dawn M. Ehde

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Pain Intensity and Pain Interference in People with Progressive Multiple Sclerosis Compared to People with Relapsing-Remitting Multiple Sclerosis

Publication date: Available online 25 May 2021

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Lindsey M. Knowles, Kala M. Phillips, Tracy E. Herring, Kevin N. Alschuler, Mark P. Jensen, Aaron P. Turner, Dawn M. Ehde

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Pain Intensity and Pain Interference in People with Progressive Multiple Sclerosis Compared to People with Relapsing-Remitting Multiple Sclerosis

Publication date: Available online 25 May 2021

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Lindsey M. Knowles, Kala M. Phillips, Tracy E. Herring, Kevin N. Alschuler, Mark P. Jensen, Aaron P. Turner, Dawn M. Ehde

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Pain Intensity and Pain Interference in People with Progressive Multiple Sclerosis Compared to People with Relapsing-Remitting Multiple Sclerosis

Publication date: Available online 25 May 2021

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Lindsey M. Knowles, Kala M. Phillips, Tracy E. Herring, Kevin N. Alschuler, Mark P. Jensen, Aaron P. Turner, Dawn M. Ehde

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Help me trust you after my misdiagnosis

Debilitating daily lifeFor more than 12 years I lived with undiagnosed chronic pain, spinal problems, pelvic floor dysfunction, gastrointestinal issues, bladder problems, bleeding tendency, and easy...

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A mediation appraisal of catastrophizing, pain-related outcomes, and race in adults with knee osteoarthritis

Symptomatic knee osteoarthritis (OA) is the most prevalent joint disease, occurring in approximately 14 million adults in the United States (US), with more than half of these cases diagnosed as advanced18. Knee OA prevalence has doubled in the US since the mid-20th century91 and is projected to further increase as a result of the aging population and the rising levels of obesity, among other risk factors18,40,83. Knee OA causes debilitating chronic joint pain, functional limitation (e.g., reduced walking distance) and disability (e.g., inability to work)5,19,38,41,72,78.

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Are cardiometabolic markers of allostatic load associated with pronociceptive processes in Native Americans?: A structural equation modeling analysis from the Oklahoma Study of Native American Pain Risk

Native Americans (NAs) experience higher rates of chronic pain than the general U.S. population, but the risk factors for this pain disparity are unknown. NAs also experience high rates of stressors and cardiovascular and metabolic health disparities (eg, diabetes, cardiovascular disease) consistent with allostatic load (stress-related wear-and-tear on homeostatic systems). Given that allostatic load is associated with chronic pain, then allostatic load may contribute to their pain disparity. Data from 302 healthy, pain-free men and women (153 NAs, 149 non-Hispanic Whites [NHW]) were analyzed using structural equation modeling to determine whether cardiometabolic allostatic load (body mass index, blood pressure, heart rate variability) mediated the relationship between NA ethnicity and experimental measures of pronociceptive processes: temporal summation of pain (TS-pain) and the nociceptive flexion reflex (TS-NFR), conditioned pain modulation of pain (CPM-pain) and NFR (CPM-NFR), and pain tolerance.

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Lack of consensus across clinical guidelines regarding the role of psychosocial factors within low back pain care: a systematic review

Low back pain (LBP) is a common health problem with detrimental consequences for both wellbeing and working capacity, and a leading global cause of disability (10). Moreover, the financial burden of LBP is enormous and for the larger part caused by costs associated with work absenteeism, presenteeism, wage replacement and more permanent incapacity for work (12,19). Over 90% of the LBP cases is considered a-specific, which means that there is no recognized pathoanatomical cause (22). Although the course of LBP is often favorable and self-limiting, recurrences are common (22) and about 50% of all LBP patients develop persisting LBP (46).

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Dysregulation in sphingolipid signaling pathways is associated with symptoms and functional connectivity of pain processing brain regions in provoked vestibulodynia

Advancements in the understanding and treatment of complex chronic pain syndromes using preclinical models and conventional clinical approaches have failed to provide relief for a significant number of affected individuals worldwide. Provoked vestibulodynia (PVD) which affects up to 16% of women is one such disorder, which is characterized by local vestibular hypersensitivity and severe pain with vaginal penetration.11 Similar to many other chronic pain conditions and providing evidence for central sensitization, PVD has been consistently linked to symptom-associated changes in brain structure and function, particularly in regions involved in pain processing and modulation (e.g., sensorimotor cortex, thalamus, amygdala, hippocampus, basal ganglia, brainstem).

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Effects of vancomycin on persistent pain-stimulated and pain-depressed behaviors in female Fischer rats with or without voluntary access to running wheels

The gut microbiome is implicated in health and the pathogenesis of disease states, including neuroinflammation and intestinal inflammatory pain 36,61. Modulation of the gut microbiome is possible via a wide variety of procedures that include antibiotic intervention and fecal microbiota transplantation (FMT). An example of the former strategy is administration of narrow- or broad-spectrum antibiotics with the goal of selective or global depletion of specific taxa, and the latter strategy of FMT from healthy donors, allows for replenishment of these bacteria in recipient hosts 2,57,60,74.

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The long-term prognosis in people with recent onset low back pain from emergency departments: an inception cohort study

Low back pain (LBP) is the world's leading cause of disability and has a high socioeconomic impact 19. The clinical course of recent-onset LBP is widely reported as favorable regarding pain and disability 9. A systematic review 9 provides evidence that most LBP episodes improve substantially within six weeks and have low group mean scores for pain and disability within one year 9. However, most studies investigating the course of recent-onset LBP included only patients from primary-care practices 8, 17, 21, 36.

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Pain and Trauma: The Role of Criterion A Trauma and Stressful Life Events in the Pain and PTSD Relationship

Pain is one of the most commonly reported health concerns of patients with post-traumatic stress disorder (PTSD), a mental health diagnosis that may occur after exposure to a traumatic event and is characterized by a constellation of symptoms including intrusive thoughts, dreams or memories, psychological distress including avoidance of reminders, and alterations in cognition, mood, and heightened arousal and reactivity. 5 A growing number of studies have shown that PTSD symptoms tend to be elevated in patients with chronic pain conditions.

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Optimizing long-term outcomes of exposure for chronic primary pain from the lens of learning theory

Exposure in vivo is a theory-driven and widely used treatment to tackle functional disability in people with chronic primary pain. Exposure is quite effective; yet, in line with exposure outcomes for anxiety disorders, a number of patients may not profit from it, or relapse. In this focus article, we critically reflect on the current exposure protocols in chronic primary pain, and provide recommendations on how to optimize them. We propose several adaptations that are expected to strengthen inhibitory learning and/or retrieval of the extinction memory, thus likely decreasing relapse.

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[Clinical Picture] Hyperparathyroidism shows its hand: findings of osteitis fibrosa cystica

A 63-year-old man attended our department reporting a 3-month history of diffuse pain in both hands. He had been investigated for primary hyperparathyroidism because of previous episodes of hypercalcaemia—the last time had necessitated hospitalisation—despite taking high doses of a calcimimetic (cinacalcet). The patient's maximum serum calcium concentration had been 13·3 mg/dL (normal range 8·5–10·5). His parathyroid hormone (286 pg/mL; normal range 12–88) and 24-h urine test for calcium (491·8 mg; normal range 100–300) had also been raised; imaging studies had been inconclusive for parathyroid hyperfunction.

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Chronic pain produces reversible memory deficits that depend on task difficulty in rats

The aversive qualities of acute pain are protective, promoting motivated behavior to evade noxious stimuli alongside inherent withdrawal reflexes. Whilst it has garnered less interest in preclinical research, another important component of this pain experience is cognition. It has been proposed that individuals have limited cognitive resources and can only attend to, learn and remember a certain amount of information at once 20. Pain seizes these cognitive resources because it is highly salient due to alerting to potential injury as well as the need to focus cognitive resources on decisions to best evade injury or promote healing 32.

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GLP-1R activation ameliorated novel-object recognition memory dysfunction via regulating hippocampal AMPK/NF-κB pathway in neuropathic pain mice

Publication date: Available online 18 May 2021

Source: Neurobiology of Learning and Memory

Author(s): Long-Qing Zhang, Wen Zhang, Ting Li, Ting Yang, Xiaoman Yuan, Yaqun Zhou, Qian Zou, Hui Yang, Feng Gao, YuKe Tian, Wei Mei, Xue-Bi Tian

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Dynamic network topological properties for classifying primary dysmenorrhea in the pain‐free phase

Abstract

Background

Primary dysmenorrhea (PDM) is known to alter brain static functional activity. This study aimed to explore the dynamic topological properties (DTP) of dynamic brain functional network in women with PDM in the pain-free phase and their performance in distinguishing PDM in the pain-free phase from healthy controls.

Methods

Thirty-five women with PDM and 38 healthy women without PDM were included. A dynamic brain functional network was constructed using the slide-window approach. The stability (TP-Stab) and variability (TP-Var) of the DTP of the dynamic functional network were computed using the graph-theory method. A support vector machine (SVM) was used to evaluate the performance of DTP in identifying PDM in the pain-free phase.

Results

Compared with healthy controls, women with PDM had not only lower TP-Stab in global DTP, which included cluster clustering coefficient (C_p ), characteristic path length (L_p ), global efficiency (E_g ), and local efficiency (E_loc ), but also lower TP-Stab and higher TP-Var in nodal DTP (nodal efficiency, E_nod ), mainly in the prefrontal cortex, anterior cingulate cortex, parahippocampal regions, and insula. The TP-Stab and TP-Var were significantly correlated with psychological variables, i.e. positive emotions, sense of control, and meaningful existence. SVM analysis showed that the DTP could identify PDM in the pain-free phase from healthy controls with an accuracy of 79.31%, sensitivity of 82.61%, and specificity of 76%.

Conclusions

Women with PDM in the pain-free phase have altered global DTP and nodal DTP, mainly involving pain-related neurocircuits. The highly variable brain network is helpful for identifying PDM in the pain-free phase.

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Dynamic network topological properties for classifying primary dysmenorrhea in the pain‐free phase

Abstract

Background

Primary dysmenorrhea (PDM) is known to alter brain static functional activity. This study aimed to explore the dynamic topological properties (DTP) of dynamic brain functional network in women with PDM in the pain-free phase and their performance in distinguishing PDM in the pain-free phase from healthy controls.

Methods

Thirty-five women with PDM and 38 healthy women without PDM were included. A dynamic brain functional network was constructed using the slide-window approach. The stability (TP-Stab) and variability (TP-Var) of the DTP of the dynamic functional network were computed using the graph-theory method. A support vector machine (SVM) was used to evaluate the performance of DTP in identifying PDM in the pain-free phase.

Results

Compared with healthy controls, women with PDM had not only lower TP-Stab in global DTP, which included cluster clustering coefficient (C_p ), characteristic path length (L_p ), global efficiency (E_g ), and local efficiency (E_loc ), but also lower TP-Stab and higher TP-Var in nodal DTP (nodal efficiency, E_nod ), mainly in the prefrontal cortex, anterior cingulate cortex, parahippocampal regions, and insula. The TP-Stab and TP-Var were significantly correlated with psychological variables, i.e. positive emotions, sense of control, and meaningful existence. SVM analysis showed that the DTP could identify PDM in the pain-free phase from healthy controls with an accuracy of 79.31%, sensitivity of 82.61%, and specificity of 76%.

Conclusions

Women with PDM in the pain-free phase have altered global DTP and nodal DTP, mainly involving pain-related neurocircuits. The highly variable brain network is helpful for identifying PDM in the pain-free phase.

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The mediating effects of pain interference on the relationships between pain intensity and possible major depression among participants with spinal cord injury

Publication date: Available online 17 May 2021

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Chao Li, Nicole D. DiPiro, Jillian Clark, James S. Krause

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Strength training in addition to neuromuscular exercise and education in individuals with knee osteoarthritis the effects on pain and sensitization

Abstract

Background

There is a lack of evidence of the relative effects of different exercise modes on pain sensitization and pain intensity in individuals with knee osteoarthritis (KOA).

Methods

Ninety individuals with radiographic and symptomatic KOA, ineligible for knee replacement surgery, were randomized to 12 weeks of twice‐weekly strength training in addition to neuromuscular exercise and education (ST+NEMEX‐EDU) or neuromuscular exercise and education alone (NEMEX‐EDU). Outcomes were bilateral, lower‐leg, cuff pressure pain‐ and tolerance thresholds (PPT, PTT), temporal summation (TS), conditioned pain modulation (CPM), self‐reported knee pain intensity, and number of painful body sites.

Results

After 12 weeks of exercise, we found significant differences in increases in PPT (‐5.01 kPa (‐8.29 to ‐1.73, p=0.0028)) and PTT (‐8.02 kPa (‐12.22 to ‐3.82, p=0.0002)) in the KOA leg in favor of ST+NEMEX‐EDU. We found no difference in effects between groups on TS, CPM or number of painful body sites. In contrast, there were significantly greater pain‐relieving effects on VAS mean knee pain during the last week (‐8.4 mm (‐16.2 to ‐0.5, p=0.0364) and during function (‐16.0 mm (‐24.8 to ‐7.3, p=0.0004)) in favor of NEMEX‐EDU after 12 weeks of exercise.

Conclusion

Additional strength training reduced pain sensitization compared to neuromuscular exercise and education alone, but also attenuated the reduction in pain intensity compared to neuromuscular exercise and education alone. The study provides the first dose‐ and type‐specific insight into the effects of a sustained exercise period on pain sensitization in KOA. Future studies are needed to elucidate the role of different exercise modes.

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Strength training in addition to neuromuscular exercise and education in individuals with knee osteoarthritis the effects on pain and sensitization

Abstract

Background

There is a lack of evidence of the relative effects of different exercise modes on pain sensitization and pain intensity in individuals with knee osteoarthritis (KOA).

Methods

Ninety individuals with radiographic and symptomatic KOA, ineligible for knee replacement surgery, were randomized to 12 weeks of twice‐weekly strength training in addition to neuromuscular exercise and education (ST+NEMEX‐EDU) or neuromuscular exercise and education alone (NEMEX‐EDU). Outcomes were bilateral, lower‐leg, cuff pressure pain‐ and tolerance thresholds (PPT, PTT), temporal summation (TS), conditioned pain modulation (CPM), self‐reported knee pain intensity, and number of painful body sites.

Results

After 12 weeks of exercise, we found significant differences in increases in PPT (‐5.01 kPa (‐8.29 to ‐1.73, p=0.0028)) and PTT (‐8.02 kPa (‐12.22 to ‐3.82, p=0.0002)) in the KOA leg in favor of ST+NEMEX‐EDU. We found no difference in effects between groups on TS, CPM or number of painful body sites. In contrast, there were significantly greater pain‐relieving effects on VAS mean knee pain during the last week (‐8.4 mm (‐16.2 to ‐0.5, p=0.0364) and during function (‐16.0 mm (‐24.8 to ‐7.3, p=0.0004)) in favor of NEMEX‐EDU after 12 weeks of exercise.

Conclusion

Additional strength training reduced pain sensitization compared to neuromuscular exercise and education alone, but also attenuated the reduction in pain intensity compared to neuromuscular exercise and education alone. The study provides the first dose‐ and type‐specific insight into the effects of a sustained exercise period on pain sensitization in KOA. Future studies are needed to elucidate the role of different exercise modes.

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Strength training in addition to neuromuscular exercise and education in individuals with knee osteoarthritis the effects on pain and sensitization

Abstract

Background

There is a lack of evidence of the relative effects of different exercise modes on pain sensitization and pain intensity in individuals with knee osteoarthritis (KOA).

Methods

Ninety individuals with radiographic and symptomatic KOA, ineligible for knee replacement surgery, were randomized to 12 weeks of twice‐weekly strength training in addition to neuromuscular exercise and education (ST+NEMEX‐EDU) or neuromuscular exercise and education alone (NEMEX‐EDU). Outcomes were bilateral, lower‐leg, cuff pressure pain‐ and tolerance thresholds (PPT, PTT), temporal summation (TS), conditioned pain modulation (CPM), self‐reported knee pain intensity, and number of painful body sites.

Results

After 12 weeks of exercise, we found significant differences in increases in PPT (‐5.01 kPa (‐8.29 to ‐1.73, p=0.0028)) and PTT (‐8.02 kPa (‐12.22 to ‐3.82, p=0.0002)) in the KOA leg in favor of ST+NEMEX‐EDU. We found no difference in effects between groups on TS, CPM or number of painful body sites. In contrast, there were significantly greater pain‐relieving effects on VAS mean knee pain during the last week (‐8.4 mm (‐16.2 to ‐0.5, p=0.0364) and during function (‐16.0 mm (‐24.8 to ‐7.3, p=0.0004)) in favor of NEMEX‐EDU after 12 weeks of exercise.

Conclusion

Additional strength training reduced pain sensitization compared to neuromuscular exercise and education alone, but also attenuated the reduction in pain intensity compared to neuromuscular exercise and education alone. The study provides the first dose‐ and type‐specific insight into the effects of a sustained exercise period on pain sensitization in KOA. Future studies are needed to elucidate the role of different exercise modes.

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Treating pain with open-label placebos: A qualitative study with post-surgical pain patients

Placebos have historically been viewed as deceptive or concealed inactive treatments, “sugar pills,” to isolate pharmacological effects of active treatment from expectancy or maturation effects in randomized controlled trials (RCTs). However, placebos have another use: as a means of treating a patient for the purpose of inducing a therapeutic placebo effect in clinical practice 6. Placebos are frequently used in this manner by physicians 16,26, and recommendations about communicating placebo effects been recently established 13.

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The Effect of Literacy-Adapted Psychosocial Treatments on Biomedical and Biopsychosocial Pain Conceptualization

The biomedical model of pain is problematic, considering that many patients continue to report pain in the absence of clinical findings, such as X-rays.19,25 Biopsychosocial models argue that pain is a multifaceted phenomenon mediated by the central nervous system and impacted by biological, psychological, social, and contextual factors.13 In fact, the Institute of Medicine (IOM) has emphasized the need to educate the public, rather than placing a singular focus on either physiological or psychological components of pain.

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Pain referral area is reduced by remote pain

Abstract

Background

Endogenous pain inhibitory mechanisms are known to reduce pain intensity, but whether they influence the size and distribution of pain referral is unclear. This study aimed to determine if referred pain is reduced by applying a remote, conditioning painful stimulus.

Methods

Twenty‐four healthy men participated in this randomized, crossover study with a control and conditioning session. Referred pain was induced from the infraspinatus muscle (dominant side) by a painful pressure for 60‐s. When applying pressure, the intensity was adjusted to a local pain intensity of 7/10 on a numerical rating scale. In the conditioning session, tonic painful pressure was simultaneously applied to the non‐dominant leg during induction of referred pain. The area of referred pain was drawn onto a digital body chart and size extracted for data analysis.

Results

For the total group and in a subgroup with distinct patterns of referred pain (n=15/24), the pain area perceived in the back and front+back, was smaller during the conditioning compared with the control (P<0.05). No significant difference was found between sessions in a subgroup only demonstrating local pain (n=9/24).

Conclusions

Engaging the descending noxious inhibitory control reduced the size of pain areas predominately when distinct pain referral was present. Assuming a conditioning effect due of descending inhibitory control acting on dorsal horn neurons, these findings may indicate that mechanisms underlying pain referral can be modulated by endogenous control. The findings may indicate that referred pain may be a useful proxy to evaluate sensitivity of central pain mechanisms as previously suggested.

Significance

The current results indicate a link between endogenous inhibition and pain referral. Descending inhibitory control effects on pain referral support a spinal mechanism involved in pain referral. Future studies should investigate whether the spatial characteristics of referred pain (e.g., size, frequency of affected body regions and distribution away from the primary nociceptive stimulus) can useful to evaluate the efficiency of endogenous pain modulation.

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Pain referral area is reduced by remote pain

Abstract

Background

Endogenous pain inhibitory mechanisms are known to reduce pain intensity, but whether they influence the size and distribution of pain referral is unclear. This study aimed to determine if referred pain is reduced by applying a remote, conditioning painful stimulus.

Methods

Twenty‐four healthy men participated in this randomized, crossover study with a control and conditioning session. Referred pain was induced from the infraspinatus muscle (dominant side) by a painful pressure for 60‐s. When applying pressure, the intensity was adjusted to a local pain intensity of 7/10 on a numerical rating scale. In the conditioning session, tonic painful pressure was simultaneously applied to the non‐dominant leg during induction of referred pain. The area of referred pain was drawn onto a digital body chart and size extracted for data analysis.

Results

For the total group and in a subgroup with distinct patterns of referred pain (n=15/24), the pain area perceived in the back and front+back, was smaller during the conditioning compared with the control (P<0.05). No significant difference was found between sessions in a subgroup only demonstrating local pain (n=9/24).

Conclusions

Engaging the descending noxious inhibitory control reduced the size of pain areas predominately when distinct pain referral was present. Assuming a conditioning effect due of descending inhibitory control acting on dorsal horn neurons, these findings may indicate that mechanisms underlying pain referral can be modulated by endogenous control. The findings may indicate that referred pain may be a useful proxy to evaluate sensitivity of central pain mechanisms as previously suggested.

Significance

The current results indicate a link between endogenous inhibition and pain referral. Descending inhibitory control effects on pain referral support a spinal mechanism involved in pain referral. Future studies should investigate whether the spatial characteristics of referred pain (e.g., size, frequency of affected body regions and distribution away from the primary nociceptive stimulus) can useful to evaluate the efficiency of endogenous pain modulation.

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Pharmacy professionals are part of the solution to reduce GPs’ workload

We are sure that many general practitioners share Salisbury’s pain about the current workload in general practice,1 but we are also confident that many general practices have discovered that having a...

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Dissecting pain processing in adolescents with Non‐Suicidal Self Injury: could suicide risk lurk among the electrodes?

Abstract

Background

Although non‐suicidal self‐injury (NSSI) disorder is highly prevalent in adolescents, its relationship with pain system function and suicidality is still controversial. The present study was designed to assess the function of the nociceptive afferent pathways and the endogenous pain modulation in adolescent patients with NSSI and to longitudinally register any suicide attempt, describe its frequency and find a possible association between suicide, neurophysiological measures, and psychological measures.

Methods

We enrolled 30 adolescents suffering from NSSI and 20 age‐ and gender‐matched healthy controls. Patients underwent a comprehensive psychological evaluation. Each participant underwent thermal‐pain thresholds of the quantitative sensory testing, laser evoked potential recording to study the ascending nociceptive pathway and the conditioned pain modulation testing to test the endogenous pain modulation.

Results

We found that patients with NSSI had a reduced amplitude of the N2 component of laser evoked potentials and an abnormal conditioned pain modulation. The amplitude of the N2 was associated with suicidal risk.

Conclusions

The deficit of the endogenous pain modulation likely depends on a saturation due to continuous pain solicitation. The strong association of a reduced amplitude of the N2 component with suicide suggests it may serve as a possible biomarker in self‐harming adolescents.

Significance

The present study, for the first time, identifies the N2 component of laser evoked potentials as a possible neurophysiological biomarker of suicidal risk in patients with non‐suicidal self‐injury, therefore raising the possibility for a non‐invasive test to identify subjects at higher risk of suicide among self‐harming patients.

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Long‐term opioid treatment and endocrine measures in chronic non‐cancer pain patients: A systematic review and meta‐analysis

Abstract

Background and Objective

Long‐term opioid treatment (L‐TOT) of chronic non‐cancer pain (CNCP) patients has been suspected to alter the endocrine system. This systematic review and meta‐analysis aimed at investigating the published evidence of L‐TOT effects on the endocrine system in adult CNCP patients.

Databases and Data Treatment

A systematic search of the literature in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the CINAHL was performed. Studies examining measures of endocrine function of the hypothalamic‐pituitary‐gonadal, ‐adrenal, ‐thyroid, ‐somatotropic and ‐prolactin axis in adult CNCP patients in L‐TOT (≥4 weeks of use) were included. Outcomes and the level of evidence were analyzed (The Cochrane Collaboration Tool, modified version of the Newcastle‐Ottawa Scale and Rating of Recommendations Assessment, Development and Evaluation working group).

Results

A total of 2660 studies were identified; 1981 excluded and finally thirteen studies (one randomized controlled trial (RCT), three longitudinal‐ and nine cross‐sectional studies) were analyzed. L‐TOT was associated with low insulin, suppression of the hypothalamic‐pituitary‐gonadal axis and alterations of the hypothalamic‐pituitary‐adrenal axis in both men and women with CNCP compared to different control groups (CNCP or healthy pain‐free). No other significant differences were reported. The studies had a high risk of bias and the overall quality of evidence was low.

Conclusion

There seems to be an impact of L‐TOT in CNCP patients on several components of the endocrine system, but the level of evidence is weak. Given the high prevalence of L‐TOT use systematic studies of larger patient populations are urgently needed.

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Seven‐year follow up of Persistent Postsurgical Pain in cardiac surgery patients: a prospective observational study of prevalence and risk factors

Abstract

Background

Our aim was to describe the long‐term prevalence, risk factors and impact on quality of life of Persistent Postsurgical Pain (PPP) following cardiac surgery.

Methods

All patients undergoing sternotomy in a single centre over a six‐month period were prospectively interviewed by telephone at six months and seven years following surgery.

Results

We analysed data from 174 patients at six months and 146 patients at seven years following surgery revealing a PPP prevalence of 39.7% (n = 69) and 9.6% (n = 14) respectively.

At six postoperative months, younger age, higher acute pain score, intraoperative remifentanil infusion and more prolonged surgery were associated with sternotomy‐site PPP. These variables, in combination, predict PPP in this study group with Area under the Receiver Operating Curve of 0.91 (95% CI 0.86‐0.94) at six months and 0.74 (95% CI 0.57‐0.86) at seven years. Quality of life scores were significantly lower with PPP (Median change in EQ‐5D score = ‐0.23 [‐0.57, ‐0.09] compared to 0.00 [0‐0.24] without PPP at seven years, p < 0.001). At seven years, younger age, prolonged surgery and intraoperative remifentanil infusion were associated with sternotomy‐site PPP.

Conclusion

To the best of our knowledge, this is the longest follow up of PPP across all surgical specialities and certainly within cardiac surgery. Prevalence of PPP and impact on QOL after cardiac surgery are high and associated with young age, high acute pain score, use of remifentanil and long operative time. We present a predictive score to highlight patients at risk of developing PPP.

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Amantadine Prevented Hypersensitivity and Decreased Oxidative Stress by NMDA Receptor Antagonism after Spinal Cord Injury in Rats.

ABSTRACT

Background

Neuropathic pain (NP) after spinal cord injury (SCI) is a disabling condition, without an effective treatment. Hyperexcitability of N‐methyl‐D‐aspartate (NMDA) receptors and oxidative stress have been reported to be associated with pain development. Amantadine, a NMDA receptor antagonist, has been proposed as a potential therapy for NP. However, its use has not been tested for NP after SCI.

Methods

In order to produce SCI, 120 female Wistar rats were used, a contusion injury to the T10 and T12 thoracic vertebrae was performed from heights of 6.25 mm and 12.5 mm. Nociceptive behavior, was evaluated with the use of von Frey filaments for 31 days. The final products of lipid peroxidation (LP) and concentration of reduced glutathione (GSH) in the injured tissue were quantified by fluorescence spectrophotometry. The antinociceptive effect of the acute (15 days after the injury) and chronic (once daily for three days immediately after the injury) with amantadine (6.25‐50 mg/Kg. I.p.) was determined. Finally, the LP and GSH were quantified in the injured tissue.

Results

Acute treatment with amantadine reduced nociceptive behavior. Concomitantly, LP was decreased by Amantadine treatment while GSH increased in the injured tissue. Similar effects were observed with chronic treatment with amantadine.

Conclusions

Data from this study suggested that the antinociceptive effects of amantadine treatment are modulated through oxidative stress and excitotoxicity reduction associated to N‐methyl‐D‐aspartate receptors activation.

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Wrist pain that should not be missed

A man in his 20s presented with generalised wrist pain one day after he tripped while playing football and landed on his outstretched and extended right hand. No deformity was found on examination,...

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Substituting Cannabidiol for Opioids and Pain Medications Among Individuals with Fibromyalgia: a Large Online Survey

Fibromyalgia (FM) is a common chronic pain condition that affects 2-4% of the population.15 People with FM typically experience widespread pain and co-occurring symptoms, including fatigue, sleep disturbances, and cognitive dysfunction.15 FM symptom management is difficult: non-pharmacological FM interventions (such as acupuncture, massage, and nutrition) are typically not covered by insurance and it can be difficult to find qualified practitioners for these non-pharmacological modalities.3, 7 Further, while there are three approved medications for FM (duloxetine, pregabalin, and milnacipran), these medications typically only result in modest pain relief carry a significant side effect burden.

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The moderating role of attention control in the relationship between pain catastrophizing and negatively-biased pain memories in youth with chronic pain

Contemporary pain theories have posited pain memories to be key in understanding deleterious pain outcomes and future pain experiences [47,55,77]. Indeed, youth with negatively-biased pain memories (i.e., recalling pain as more intense or fearful than initially reported) are at risk for experiencing more pain, anxiety and distress during subsequent pain experiences [9,45,47,51,53]. Furthermore, negative or distressing pain memories are predictive of fear and avoidance of medical care in adulthood [56] and have been posited to underlie the transition from acute to chronic pain [20,51,66].

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A Preliminary Study of Provider Burden in the Treatment of Chronic Pain: Perspectives of Physicians and People with Chronic Pain

People who live with chronic pain can face numerous challenges, and the challenges of managing severe pain, with its associated distress and disability, now are well-recognized.43 A report from the Institute of Medicine28 and the more recent National Pain Strategy29 both recognize multiple societal issues that add to the significant adversities faced by people living with chronic pain. Those include, among others, racial/ethnic and socioeconomic disparities in care, healthcare delivery systems that often disadvantage multidisciplinary treatment, and insufficient knowledge of chronic pain and its treatment at both professional and community levels.

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The effect of experimental and clinical musculoskeletal pain on spinal and supraspinal projections to motoneurons and motor unit properties in humans: a systematic review

ABSTRACT

Background and Objective

Numerous studies have examined the influence of pain on spinal reflex excitability, motor unit behaviour and corticospinal excitability. Nevertheless, there are inconsistencies in the conclusions made. This systematic review sought to understand the effect of pain on spinal and supraspinal projections to motoneurons and motor unit properties by examining the influence of clinical or experimental pain on the following three domains: H reflex, corticospinal excitability and motor unit properties.

Databases and Data Treatment

MeSH terms and preselected keywords relating to the H reflex, motor evoked potentials and motor unit decomposition in chronic and experimental pain were used to perform a systematic literature search using CINAHL, EMBASE, Web of Science, Medline, Google Scholar, and Scopus databases. Two independent reviewers screened papers for inclusion and assessed the methodological quality using a modified Downs and Black risk of bias tool; a narrative synthesis and three meta‐analyses were performed.

Results

Sixty‐one studies were included and 17 different outcome variables were assessed across the three domains. Both experimental and clinical pain has no major influence on measures of the H reflex whereas experimental and clinical pain appeared to have differing effects on corticospinal excitability. Experimental pain consistently reduced motor unit discharge rate, a finding which was not consistent with data obtained from patients. The results indicate that when in tonic pain, induced via experimental pain models, inhibitory effects on motoneuron behaviour were evident. However, in chronic clinical pain populations, more varied responses were evident likely reflecting individual adaptations to chronic symptoms.

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Human surrogate models of central sensitization: A critical review and practical guide

Abstract

Background

As in other fields of medicine, development of new medications for management of neuropathic pain has been difficult since preclinical rodent models do not necessarily translate to the clinics. Aside from ongoing pain with burning or shock‐like qualities, neuropathic pain is often characterized by pain hypersensitivity (hyperalgesia and allodynia), most often towards mechanical stimuli, reflecting sensitization of neural transmission.

Data treatment

We therefore performed a systematic literature review (PubMed‐Medline, Cochrane, WoS, ClinicalTrials) and semi‐quantitative meta‐analysis of human pain models that aim to induce central sensitization, and generate hyperalgesia surrounding a real or simulated injury.

Results

From an initial set of 1569 reports, we identified and analysed 269 studies using more than a dozen human models of sensitization. Five of these models (intradermal or topical capsaicin, low‐ or high‐frequency electrical stimulation, thermode‐induced heat‐injury) were found to reliably induce secondary hyperalgesia to pinprick and have been implemented in multiple laboratories. The ability of these models to induce dynamic mechanical allodynia was however substantially lower. The proportion of subjects who developed hypersensitivity was rarely provided, giving rise to significant reporting bias. In four of these models pharmacological profiles allowed to verify similarity to some clinical conditions, and therefore may inform basic research for new drug development.

Conclusions

While there is no single “optimal” model of central sensitization, the range of validated and easy‐to‐use procedures in humans should be able to inform preclinical researchers on helpful potential biomarkers, thereby narrowing the translation gap between basic and clinical data.

Significance

Being able to mimic aspects of pathological pain directly in humans has a huge potential to understand pathophysiology and provide animal research with translatable biomarkers for drug development. One group of human surrogate models has proven to have excellent predictive validity: they respond to clinically active medications and do not respond to clinically inactive medications, including some that worked in animals but failed in the clinics. They should therefore inform basic research for new drug development.

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The effect of experimental and clinical musculoskeletal pain on spinal and supraspinal projections to motoneurons and motor unit properties in humans: a systematic review

ABSTRACT

Background and Objective

Numerous studies have examined the influence of pain on spinal reflex excitability, motor unit behaviour and corticospinal excitability. Nevertheless, there are inconsistencies in the conclusions made. This systematic review sought to understand the effect of pain on spinal and supraspinal projections to motoneurons and motor unit properties by examining the influence of clinical or experimental pain on the following three domains: H reflex, corticospinal excitability and motor unit properties.

Databases and Data Treatment

MeSH terms and preselected keywords relating to the H reflex, motor evoked potentials and motor unit decomposition in chronic and experimental pain were used to perform a systematic literature search using CINAHL, EMBASE, Web of Science, Medline, Google Scholar, and Scopus databases. Two independent reviewers screened papers for inclusion and assessed the methodological quality using a modified Downs and Black risk of bias tool; a narrative synthesis and three meta‐analyses were performed.

Results

Sixty‐one studies were included and 17 different outcome variables were assessed across the three domains. Both experimental and clinical pain has no major influence on measures of the H reflex whereas experimental and clinical pain appeared to have differing effects on corticospinal excitability. Experimental pain consistently reduced motor unit discharge rate, a finding which was not consistent with data obtained from patients. The results indicate that when in tonic pain, induced via experimental pain models, inhibitory effects on motoneuron behaviour were evident. However, in chronic clinical pain populations, more varied responses were evident likely reflecting individual adaptations to chronic symptoms.

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Human surrogate models of central sensitization: A critical review and practical guide

Abstract

Background

As in other fields of medicine, development of new medications for management of neuropathic pain has been difficult since preclinical rodent models do not necessarily translate to the clinics. Aside from ongoing pain with burning or shock‐like qualities, neuropathic pain is often characterized by pain hypersensitivity (hyperalgesia and allodynia), most often towards mechanical stimuli, reflecting sensitization of neural transmission.

Data treatment

We therefore performed a systematic literature review (PubMed‐Medline, Cochrane, WoS, ClinicalTrials) and semi‐quantitative meta‐analysis of human pain models that aim to induce central sensitization, and generate hyperalgesia surrounding a real or simulated injury.

Results

From an initial set of 1569 reports, we identified and analysed 269 studies using more than a dozen human models of sensitization. Five of these models (intradermal or topical capsaicin, low‐ or high‐frequency electrical stimulation, thermode‐induced heat‐injury) were found to reliably induce secondary hyperalgesia to pinprick and have been implemented in multiple laboratories. The ability of these models to induce dynamic mechanical allodynia was however substantially lower. The proportion of subjects who developed hypersensitivity was rarely provided, giving rise to significant reporting bias. In four of these models pharmacological profiles allowed to verify similarity to some clinical conditions, and therefore may inform basic research for new drug development.

Conclusions

While there is no single “optimal” model of central sensitization, the range of validated and easy‐to‐use procedures in humans should be able to inform preclinical researchers on helpful potential biomarkers, thereby narrowing the translation gap between basic and clinical data.

Significance

Being able to mimic aspects of pathological pain directly in humans has a huge potential to understand pathophysiology and provide animal research with translatable biomarkers for drug development. One group of human surrogate models has proven to have excellent predictive validity: they respond to clinically active medications and do not respond to clinically inactive medications, including some that worked in animals but failed in the clinics. They should therefore inform basic research for new drug development.

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The effect of experimental and clinical musculoskeletal pain on spinal and supraspinal projections to motoneurons and motor unit properties in humans: a systematic review

ABSTRACT

Background and Objective

Numerous studies have examined the influence of pain on spinal reflex excitability, motor unit behaviour and corticospinal excitability. Nevertheless, there are inconsistencies in the conclusions made. This systematic review sought to understand the effect of pain on spinal and supraspinal projections to motoneurons and motor unit properties by examining the influence of clinical or experimental pain on the following three domains: H reflex, corticospinal excitability and motor unit properties.

Databases and Data Treatment

MeSH terms and preselected keywords relating to the H reflex, motor evoked potentials and motor unit decomposition in chronic and experimental pain were used to perform a systematic literature search using CINAHL, EMBASE, Web of Science, Medline, Google Scholar, and Scopus databases. Two independent reviewers screened papers for inclusion and assessed the methodological quality using a modified Downs and Black risk of bias tool; a narrative synthesis and three meta‐analyses were performed.

Results

Sixty‐one studies were included and 17 different outcome variables were assessed across the three domains. Both experimental and clinical pain has no major influence on measures of the H reflex whereas experimental and clinical pain appeared to have differing effects on corticospinal excitability. Experimental pain consistently reduced motor unit discharge rate, a finding which was not consistent with data obtained from patients. The results indicate that when in tonic pain, induced via experimental pain models, inhibitory effects on motoneuron behaviour were evident. However, in chronic clinical pain populations, more varied responses were evident likely reflecting individual adaptations to chronic symptoms.

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Human surrogate models of central sensitization: A critical review and practical guide

Abstract

Background

As in other fields of medicine, development of new medications for management of neuropathic pain has been difficult since preclinical rodent models do not necessarily translate to the clinics. Aside from ongoing pain with burning or shock‐like qualities, neuropathic pain is often characterized by pain hypersensitivity (hyperalgesia and allodynia), most often towards mechanical stimuli, reflecting sensitization of neural transmission.

Data treatment

We therefore performed a systematic literature review (PubMed‐Medline, Cochrane, WoS, ClinicalTrials) and semi‐quantitative meta‐analysis of human pain models that aim to induce central sensitization, and generate hyperalgesia surrounding a real or simulated injury.

Results

From an initial set of 1569 reports, we identified and analysed 269 studies using more than a dozen human models of sensitization. Five of these models (intradermal or topical capsaicin, low‐ or high‐frequency electrical stimulation, thermode‐induced heat‐injury) were found to reliably induce secondary hyperalgesia to pinprick and have been implemented in multiple laboratories. The ability of these models to induce dynamic mechanical allodynia was however substantially lower. The proportion of subjects who developed hypersensitivity was rarely provided, giving rise to significant reporting bias. In four of these models pharmacological profiles allowed to verify similarity to some clinical conditions, and therefore may inform basic research for new drug development.

Conclusions

While there is no single “optimal” model of central sensitization, the range of validated and easy‐to‐use procedures in humans should be able to inform preclinical researchers on helpful potential biomarkers, thereby narrowing the translation gap between basic and clinical data.

Significance

Being able to mimic aspects of pathological pain directly in humans has a huge potential to understand pathophysiology and provide animal research with translatable biomarkers for drug development. One group of human surrogate models has proven to have excellent predictive validity: they respond to clinically active medications and do not respond to clinically inactive medications, including some that worked in animals but failed in the clinics. They should therefore inform basic research for new drug development.

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Authors’ reply to the comment by Russo et al.

Abstract

We would like to thank Dr. Russo and colleagues (Russo et al., 2021) for their interest in our publication (Pushparaj et al., 2021) and for their insightful comments. Dr. Russo and his colleagues are correct in stating our meta‐analysis of 7 RCTs did not show analgesic benefit of pulsed radiofrequency [pRF] neuromodulation for chronic shoulder pain over conservative medical management [CMM]. As noted by Dr. Russo and colleagues, heterogeneity in “conventional medical management” in the included studies was considerable. Though a meta‐analysis that does not include the data from Eyigor study (Eyigor et al., 2010) may yield different results, we recommend focusing on the qualitative analysis of the results as summarized in the letter by Dr. Russo et al.

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Anti‐hypersensitivity effect of betanin (red beetroot extract) via modulation of microglial activation in a mouse model of neuropathic pain

Abstract

Background

Neuropathic pain (NeP) medications have several side effects that affect NeP patients’ quality of life. Betanin, the most common betacyanin pigment, has been shown to have potent antioxidant and anti‐inflammatory properties in vivo; thus, it has potential as a healthcare treatment. In this study, we focused on betanin (red beetroot extract) as a potential therapy for NeP.

Methods

Mice model of neuropathic pain were made by chronic constriction injury (CCI), and the development of mechanical hypersensitivity was confirmed using the von Frey test. Motor coordination and locomotor activity were assessed using open field tests and rotarod tests, respectively. The expression level of glial markers in the spinal cords was analyzed by immunostaining. The direct effects of betanin on microglial cells were investigated using primary cultured microglial cells.

Results

In CCI model mice, repeated betanin treatment, both intraperitoneally and orally, attenuated developing mechanical hypersensitivity in a dose‐dependent manner without impairing motor coordination. Betanin treatment also attenuated mechanical hypersensitivity that had developed and prevented the onset of mechanical hypersensitivity in CCI mice. Microglial activation in the spinal cord is known to play a key role in the development of NeP; betanin treatment reduced CCI‐induced microglial activation in the spinal cord of model mice. Moreover, in primary microglia cultured cells, the activation of microglia by lipopolysaccharide application was suppressed by betanin treatment.

Conclusion

Betanin treatment appears to ameliorate mechanical hypersensitivity related to CCI‐induced NeP in mice by inhibiting microglial activation.

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Is Europe also facing an opioid crisis? ‐ A survey of European Pain Federation chapters

Abstract

Background

There is considerable public interest in whether Europe is facing an opioid crisis comparable to the one in the U.S. and the contribution of opioid prescriptions for pain to a potential opioid crisis.

Methods

A task force of the European Pain Federation (EFIC) conducted a survey with its national chapter representatives on trends of opioid prescriptions and of drug‐related emergency departments and substance use disorder treatment admissions and of deaths as proxies of opioid‐related harms over the last twenty years.

Results

Data from 25 European countries were received. In most European countries opioid prescriptions increased from 2004 to 2016. The levels of opioid consumption and their increase differed between countries. Some Eastern European countries still have a low opioid consumption. Opioids are mainly prescribed for acute pain and chronic noncancer pain in some Western and Northern European countries. There was a parallel increase of opioid prescriptions and some proxies of opioid‐related harms in France, Finland and the Netherlands, but not in Germany, Spain and Norway. In U.K., opioid overdose deaths, but not opioid prescriptions increased between 2016 and 2018.There are no robust data available on whether prescribed opioids for pain patients contributed to opioid‐related harms.

Conclusions

There are marked differences between European countries in trends of opioid prescribing and of proxies for opioid‐related harms. Europe as a whole is not facing an opioid crisis. Discussions on the potential harms of opioids should not obstruct their prescription for cancer pain and palliative care.

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Authors’ reply to the comment by Russo et al.

Abstract

We would like to thank Dr. Russo and colleagues (Russo et al., 2021) for their interest in our publication (Pushparaj et al., 2021) and for their insightful comments. Dr. Russo and his colleagues are correct in stating our meta‐analysis of 7 RCTs did not show analgesic benefit of pulsed radiofrequency [pRF] neuromodulation for chronic shoulder pain over conservative medical management [CMM]. As noted by Dr. Russo and colleagues, heterogeneity in “conventional medical management” in the included studies was considerable. Though a meta‐analysis that does not include the data from Eyigor study (Eyigor et al., 2010) may yield different results, we recommend focusing on the qualitative analysis of the results as summarized in the letter by Dr. Russo et al.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/2SqEUja
via IFTTT

Anti‐hypersensitivity effect of betanin (red beetroot extract) via modulation of microglial activation in a mouse model of neuropathic pain

Abstract

Background

Neuropathic pain (NeP) medications have several side effects that affect NeP patients’ quality of life. Betanin, the most common betacyanin pigment, has been shown to have potent antioxidant and anti‐inflammatory properties in vivo; thus, it has potential as a healthcare treatment. In this study, we focused on betanin (red beetroot extract) as a potential therapy for NeP.

Methods

Mice model of neuropathic pain were made by chronic constriction injury (CCI), and the development of mechanical hypersensitivity was confirmed using the von Frey test. Motor coordination and locomotor activity were assessed using open field tests and rotarod tests, respectively. The expression level of glial markers in the spinal cords was analyzed by immunostaining. The direct effects of betanin on microglial cells were investigated using primary cultured microglial cells.

Results

In CCI model mice, repeated betanin treatment, both intraperitoneally and orally, attenuated developing mechanical hypersensitivity in a dose‐dependent manner without impairing motor coordination. Betanin treatment also attenuated mechanical hypersensitivity that had developed and prevented the onset of mechanical hypersensitivity in CCI mice. Microglial activation in the spinal cord is known to play a key role in the development of NeP; betanin treatment reduced CCI‐induced microglial activation in the spinal cord of model mice. Moreover, in primary microglia cultured cells, the activation of microglia by lipopolysaccharide application was suppressed by betanin treatment.

Conclusion

Betanin treatment appears to ameliorate mechanical hypersensitivity related to CCI‐induced NeP in mice by inhibiting microglial activation.

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Is Europe also facing an opioid crisis? ‐ A survey of European Pain Federation chapters

Abstract

Background

There is considerable public interest in whether Europe is facing an opioid crisis comparable to the one in the U.S. and the contribution of opioid prescriptions for pain to a potential opioid crisis.

Methods

A task force of the European Pain Federation (EFIC) conducted a survey with its national chapter representatives on trends of opioid prescriptions and of drug‐related emergency departments and substance use disorder treatment admissions and of deaths as proxies of opioid‐related harms over the last twenty years.

Results

Data from 25 European countries were received. In most European countries opioid prescriptions increased from 2004 to 2016. The levels of opioid consumption and their increase differed between countries. Some Eastern European countries still have a low opioid consumption. Opioids are mainly prescribed for acute pain and chronic noncancer pain in some Western and Northern European countries. There was a parallel increase of opioid prescriptions and some proxies of opioid‐related harms in France, Finland and the Netherlands, but not in Germany, Spain and Norway. In U.K., opioid overdose deaths, but not opioid prescriptions increased between 2016 and 2018.There are no robust data available on whether prescribed opioids for pain patients contributed to opioid‐related harms.

Conclusions

There are marked differences between European countries in trends of opioid prescribing and of proxies for opioid‐related harms. Europe as a whole is not facing an opioid crisis. Discussions on the potential harms of opioids should not obstruct their prescription for cancer pain and palliative care.

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[Clinical Picture] Adrenalitis and anasarca in idiopathic multicentric Castleman's disease

A 46-year-old man presented to our hospital with abdominal pain and fever. In his medical history he reported three previous episodes of varicella zoster. On examination, he had a temperature of 38·3°C, small cervical lymph nodes, and some right upper quadrant tenderness.

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Validation of the Bath CRPS Body Perception Disturbance Scale

Complex Regional Pain Syndrome (CRPS) is characterized by pain; and autonomic, sensory, and motor symptoms affecting one or more limb(s). An estimated 70-90% of people with CRPS report disturbances in their body perception.20 These disturbances can involve mismatches between the actual and perceived position, size, weight, pressure, or temperature of the affected limb.29 People with CRPS may also report that their affected limb feels detached from the rest of their body; or that they avoid looking at, experience negative emotions towards, or have a desire to amputate it.

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The efficacy of an educational movie to improve pain and dysfunctional behavior in school children: A randomized controlled trial

Abstract

Background

Chronic pain in children is a serious issue, therefore calling for effective prevention/intervention measures. This study aimed to evaluate the efficacy of an educational movie on pain knowledge in school children in general and on pain‐related behaviours and pain intensity in those who are affected by chronic pain. Regarding those affected, the association between pain knowledge and intensity, as well as the potential mediating effect of pain‐related behaviours, were investigated.

Methods

Recruited from four schools, N = 381 students (51.7% female; M _age = 11.4, SD = 0.95) participated, of which n = 108 reported chronic pain. Each school was randomly allocated to the intervention or control group (cluster‐randomization). At two time points spaced 4–5 weeks apart, students provided information on their pain knowledge, pain‐related behaviour (passive pain coping, pain‐related disability, missed school days, medication use) and pain intensity. After the first assessment, students in the intervention group watched an educational movie. Multilevel linear models for all outcomes were calculated as well as a mediation analysis.

Results

Pain knowledge increased significantly in the intervention group (β = 2.76 [95% CI 2.20, 3.31]). However, no significant time‐by‐group interactions were found for pain‐related behaviour or pain intensity. The mediation model identified that the indirect effect of pain knowledge on pain intensity was mediated by pain‐related behaviour (β = −0.18, p = 0.014 and β = 0.38, p < 0.001, respectively).

Conclusions

Educational movies may be an effective tool for educating students about pain management. However, the knowledge gained may not be sufficient to improve pain behaviour and intensity overall.

Significance

A 10‐min educational movie on chronic pain management was tested in school children (N = 381). Following the intervention, knowledge of chronic pain concepts was statistically greater in the intervention group compared to the control group not watching the movie. Furthermore, a mediation model theoretically determined whether an association between pain knowledge and pain intensity exists, and whether this is explained by level of dysfunctional pain‐related behaviorisms. Full mediation was confirmed.

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The efficacy of an educational movie to improve pain and dysfunctional behavior in school children: A randomized controlled trial

Abstract

Background

Chronic pain in children is a serious issue, therefore calling for effective prevention/intervention measures. This study aimed to evaluate the efficacy of an educational movie on pain knowledge in school children in general and on pain‐related behaviours and pain intensity in those who are affected by chronic pain. Regarding those affected, the association between pain knowledge and intensity, as well as the potential mediating effect of pain‐related behaviours, were investigated.

Methods

Recruited from four schools, N = 381 students (51.7% female; M _age = 11.4, SD = 0.95) participated, of which n = 108 reported chronic pain. Each school was randomly allocated to the intervention or control group (cluster‐randomization). At two time points spaced 4–5 weeks apart, students provided information on their pain knowledge, pain‐related behaviour (passive pain coping, pain‐related disability, missed school days, medication use) and pain intensity. After the first assessment, students in the intervention group watched an educational movie. Multilevel linear models for all outcomes were calculated as well as a mediation analysis.

Results

Pain knowledge increased significantly in the intervention group (β = 2.76 [95% CI 2.20, 3.31]). However, no significant time‐by‐group interactions were found for pain‐related behaviour or pain intensity. The mediation model identified that the indirect effect of pain knowledge on pain intensity was mediated by pain‐related behaviour (β = −0.18, p = 0.014 and β = 0.38, p < 0.001, respectively).

Conclusions

Educational movies may be an effective tool for educating students about pain management. However, the knowledge gained may not be sufficient to improve pain behaviour and intensity overall.

Significance

A 10‐min educational movie on chronic pain management was tested in school children (N = 381). Following the intervention, knowledge of chronic pain concepts was statistically greater in the intervention group compared to the control group not watching the movie. Furthermore, a mediation model theoretically determined whether an association between pain knowledge and pain intensity exists, and whether this is explained by level of dysfunctional pain‐related behaviorisms. Full mediation was confirmed.

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The efficacy of an educational movie to improve pain and dysfunctional behavior in school children: A randomized controlled trial

Abstract

Background

Chronic pain in children is a serious issue, therefore calling for effective prevention/intervention measures. This study aimed to evaluate the efficacy of an educational movie on pain knowledge in school children in general and on pain‐related behaviours and pain intensity in those who are affected by chronic pain. Regarding those affected, the association between pain knowledge and intensity, as well as the potential mediating effect of pain‐related behaviours, were investigated.

Methods

Recruited from four schools, N = 381 students (51.7% female; M _age = 11.4, SD = 0.95) participated, of which n = 108 reported chronic pain. Each school was randomly allocated to the intervention or control group (cluster‐randomization). At two time points spaced 4–5 weeks apart, students provided information on their pain knowledge, pain‐related behaviour (passive pain coping, pain‐related disability, missed school days, medication use) and pain intensity. After the first assessment, students in the intervention group watched an educational movie. Multilevel linear models for all outcomes were calculated as well as a mediation analysis.

Results

Pain knowledge increased significantly in the intervention group (β = 2.76 [95% CI 2.20, 3.31]). However, no significant time‐by‐group interactions were found for pain‐related behaviour or pain intensity. The mediation model identified that the indirect effect of pain knowledge on pain intensity was mediated by pain‐related behaviour (β = −0.18, p = 0.014 and β = 0.38, p < 0.001, respectively).

Conclusions

Educational movies may be an effective tool for educating students about pain management. However, the knowledge gained may not be sufficient to improve pain behaviour and intensity overall.

Significance

A 10‐min educational movie on chronic pain management was tested in school children (N = 381). Following the intervention, knowledge of chronic pain concepts was statistically greater in the intervention group compared to the control group not watching the movie. Furthermore, a mediation model theoretically determined whether an association between pain knowledge and pain intensity exists, and whether this is explained by level of dysfunctional pain‐related behaviorisms. Full mediation was confirmed.

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Sex Differences, Sleep Disturbance and Risk of Persistent Pain Associated With Groin Hernia Surgery: A Nationwide Register-Based Cohort Study

Surgical trauma exposes patients to a substantial risk for life-altering persistent pain. In particular major surgery, e.g., amputation, thoracotomy and mastectomy, carries a high risk for development of chronic postsurgical pain (CPSP), but groin hernia repair also entails high incidences of debilitating pain.35 As the global surgical volume increases rapidly, the problem of CPSP is immense.70 Groin hernia repair is one of the most common surgical procedures worldwide, with more than 20 million operations performed each year.

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Sensory innervation of human bone: an immunohistochemical study to further understand bone pain

Musculoskeletal diseases are highly prevalent in the general population and are a leading cause of disability among patients and medical costs every year.5,21,32,34,44,58 Diseases affecting bone and their (surgical) treatment can lead to considerable pain.18 Bone pain negatively affects mobility, inhibits rehabilitation, and can lead to long-term disabilities.12,13,42,50,53,62,63 The complex underlying mechanisms and multiple possible etiologies of bone pain, make this pain difficult to attenuate.

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Non‐invasive Management of Soft Tissue Disorders of the Shoulder: A Clinical Practice Guideline from the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration

ABSTRACT

Objectives

To develop an evidence‐based guideline for the non‐invasive management of soft tissue disorders of the shoulder (shoulder pain), excluding major pathology.

Methods

This guideline is based on high‐quality evidence from seven systematic reviews. Multidisciplinary experts considered the evidence of effectiveness, safety, cost‐effectiveness, societal and ethical values, and patient experiences when formulating recommendations. Target audience is clinicians; target population is adults with shoulder pain.

Results

When managing patients with shoulder pain, clinicians should 1) rule out major structural or other pathologies as the cause of shoulder pain and reassure patients about the benign and self‐limited nature of most soft tissue shoulder pain; 2) develop a care plan in partnership with the patient; 3) For shoulder pain of any duration, consider low‐level laser therapy; multimodal care (heat/cold, joint mobilization, and range of motion exercise); cervicothoracic spine manipulation and mobilization for shoulder pain when associated pain or restricted movement of the cervicothoracic spine; or thoracic spine manipulation; 4) For shoulder pain > 3 months duration, consider stretching and/or strengthening exercises; laser acupuncture; or general physician care (information, advice, and pharmacological pain management if necessary); 5) For shoulder pain with calcific tendinitis on imaging, consider shock‐wave therapy; 6) For shoulder pain of any duration, do not offer ultrasound; taping; interferential current therapy; diacutaneous fibrolysis; soft tissue massage; or cervicothoracic spine manipulation and mobilization as an adjunct to exercise (i.e., range of motion, strengthening and stretching exercise) for pain between the neck and the elbow at rest or during movement of the arm; 7) For shoulder pain >3 months duration, do not offer shock‐wave therapy; and 8) should reassess the patient’s status at each visit for worsening of symptoms or new physical, mental, or psychological symptoms, or satisfactory recovery.

Conclusions

Our evidence‐based guideline provides recommendations for non‐invasive management of shoulder pain. The impact of the guideline in clinical practice requires further evaluation.

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