Background: The study of pain at rest (PAR) and movement-evoked pain (MEP) in persons with musculoskeletal pain has received substantial attention. Despite strong interest, relatively little attention has been directed to the psychometric development of these constructs. Our purpose was to explore the relationship between PAR and MEP and to examine the prognostic utility of these measures in persons with knee arthroplasty.
Methods: We used prospectively collected data from persons scheduled for knee arthroplasty who had moderate to high levels of pain catastrophizing. Preoperative latent variables for PAR and MEP were developed and used to determine if they were associated with a binary latent variable of good versus poor pain and function outcome trajectories. Factor correlations were used to determine the extent to which the variance for PAR and MEP was overlapping.
Results: PAR and MEP are significant predictors of good versus poor pain and function classes. Odds ratios ranged from 1.21 to 1.64 (p < 0.001) indicating a significant increase in the likelihood of poor outcome. Correlation between PAR and MEP latent variables was high (r = 0.89; 95% CI: 0.86-0.92) indicating substantially overlapping variance.
Conclusions: PAR and MEP, as defined in our study, can be used to make prognostic judgements regarding risk of poor postoperative outcome trajectory following knee arthroplasty. However, PAR and MEP showed substantially overlapping variance indicating that measurements of both are not necessary when making prognostic assessments.
Significance statement: Preoperative PAR and MEP latent variables, as defined in our study, had prognostic significance for 1 year pain and function outcome trajectories. PAR and MEP latent variables had substantially overlapping variance which suggested that only one is needed to make prognostic judgements. The prognostic significance of PAR and MEP as well as their substantially overlapping variance is new to the field prognostic research in knee arthroplasty.
Background: Adolescent chronic pain is a substantial public health problem, and pain symptoms often persist into adulthood. Young adults with chronic pain are at elevated risk for more frequent tobacco, alcohol and cannabis use, and cross-sectional research highlights the importance of psychosocial vulnerability factors. Limited research has examined how adolescent predictors, including mental health symptoms, pain, sleep and family functioning, impact later, young adult substance use.
Methods: A prospective cohort of 229 young adults (77.3% female; Mage = 21.0, SD = 1.6) with childhood-onset chronic pain completed measurements in adolescence and a follow-up assessment in young adulthood of past 3-month substance use frequency.
Results: Adolescent sleep quality and male sex were associated with more frequent tobacco use; adolescent depression was associated with more frequent alcohol use, and adolescent pain severity was associated with less frequent, and male sex was associated with more frequent cannabis use.
Conclusions: Adolescent predictors of young adult substance use among youth with childhood-onset chronic pain represent important factors that may inform assessment, prevention and treatment of substance use in this population. Identifying and testing psychological interventions that target these vulnerability factors may reduce overall substance use risk in young adulthood.
Significance: This prospective observational study of young adults with childhood-onset chronic pain identified adolescent depression and sleep quality as vulnerability factors associated with substance use. Given the increasing risk for substance use during adolescence and young adulthood, these findings highlight the potential importance of early intervention to reduce substance use among young adults with childhood-onset chronic pain.
Background: Sensory profiling in neuropathic pain using quantitative sensory testing (QST) has not been extended to central neuropathic pain due to spinal cord injury (SCI). This study aims to fill this gap by evaluating sensory profiles in patients with neuropathic SCI pain.
Method: We retrospectively analysed consecutive QST data from 62 patients with neuropathic spinal cord injury pain (SCIP), following the German Research Network on Neuropathic Pain protocol. The study included at-level and below-level SCIP due to a spinal cord lesion, and at-level SCIP following a cauda equina lesion. QST parameters were compared between diagnostic groups. QST profiles of below-level SCIP (central neuropathic pain) were manually assigned to sensory phenotypes based on literature and expert opinion.
Results: No statistical difference in QST parameters between pain diagnoses was found. For central neuropathic pain (below-level SCIP), three phenotypes were descriptively observed: loss of function (59%), thermal and mechanical hyperalgesia combination (16%), and mechanical hyperalgesia (19%). The remaining 5% of patients did not fit a common pattern. There was no statistical difference in clinical and psychological variables between phenotypes. In a subgroup analysis, the loss of function phenotype weakly correlated with older age, longer time since injury, and longer pain duration.
Conclusions: Here, we capture sensory phenotypes of central neuropathic pain following SCI. The limited sample size, high rate of missing values, and the retrospective nature of the study mean that results should be seen as strictly exploratory. Further research should replicate these findings and explore the significance of phenotypes.
Significance statement: The evaluation of sensory phenotypes by quantitative sensory testing in central neuropathic pain due to SCI adds a new perspective on sensory phenotypes in comparison to peripheral neuropathic pain. The described thermal and mechanical hyperalgesia combination might represent involvement of the spinothalamic tract. In addition, there was a trend towards older age and longer time since injury in patients with loss of function.
Background: The lead symptom of small fibre neuropathy (SFN) is neuropathic pain. Recent functional magnetic resonance imaging (fMRI) studies have indicated central changes in SFN patients of different etiologies. However, less is known about brain functional connectivity during acute pain processing in idiopathic SFN.
Methods: We conducted fMRI with thermal heat pain application (left volar forearm) in 32 idiopathic SFN patients and 31 healthy controls. We performed functional connectivity analyses with right supplementary motor area (SMA), left insula, and left caudate nucleus (CN) as seed regions, respectively. Since pathogenic gain-of-function variants in voltage gated sodium channels (Nav) have been linked to SFN pathophysiology, explorative connectivity analyses were performed in a homogenous subsample of patients carrying rare heterozygous missense variants.
Results: For right SMA, we found significantly higher connectivity with the right thalamus in SFN patients compared to controls. This connectivity correlated significantly with intraepidermal nerve fibre density, suggesting a link between peripheral and central pain processing. We found significantly reduced connections between right SMA and right middle frontal gyrus in patients with Nav variants. Likewise, connectivity between left CN and right frontal pole was decreased.
Conclusions: Aberrant functional connectivity in SFN is in line with previous research on other chronic pain syndromes. Functional connectivity changes may be linked to SFN, highlighting the need to determine if they result from peripheral changes causing abnormal somatosensory processing. This understanding may be crucial for assessing their impact on painful symptoms and therapy response.
Significance statement: We found increased functional connectivity between SMA and thalamus during painful stimulation in patients with idiopathic SFN. Connectivity correlated significantly with intraepidermal nerve fibre density, suggesting a link between peripheral and central pain processing. Our findings emphasize the importance of investigating functional connectivity changes as a potential feature of SFN.
Background: Painful neuropathy is a pathological condition caused by numerous factors including diabetes, chemotherapy or cancer. ART26.12 is a novel fatty acid-binding protein 5 inhibitor, which our group showed could prevent and treat persistent pain in a preclinical model of oxaliplatin-induced peripheral neuropathy.
Methods: In the current study, the efficacy of orally dosed ART26.12 was tested in multiple neuropathy models of different aetiology. Paw withdrawal threshold to von Frey monofilaments and latency to escape a cold plate were used as measurements of mechanical and cold sensitivity.
Results: ART26.12 (25 and 50 mg/kg BID), dosed prior to the induction of paclitaxel-induced peripheral neuropathy (PIPN), reversed mechanical allodynia induced by paclitaxel in both male and female rats, and ART26.12 (50 mg/kg BID) prevented the induction of PIPN in female rats. ART26.12 (50 mg/kg BID) also had a protective effect on body weight in the PIPN model. ART26.12 (25 and 100 mg/kg BID) reversed mechanical allodynia when treating established streptozotocin-induced diabetic neuropathy in male rats. In a model of breast cancer-induced bone pain in female rats, ART26.12 (100 mg/kg BID) reversed mechanical allodynia within 1 h of dosing. In the same model, ART26.12 (25 mg/kg BID) reversed mechanical allodynia from day 4 of treatment.
Conclusion: Overall, these preclinical data suggest that ART26.12 is a safe and efficacious therapeutic drug for continued development towards the prevention and treatment of peripheral neuropathy.
Significance statement: This work now shows that ART26.12, a novel and selective inhibitor of FABP5, can prevent and treat multiple preclinical models of peripheral neuropathy. Given its excellent safety profile, further work is warranted to develop ART26.12 as a potential therapeutic tool for pain management.
Background: Trunk co-contraction during lifting may reflect a guarded motor response to a threatening task. This work estimated the impact of pain catastrophizing on trunk co-contraction during lifting, in people with and without low back pain.
Methods: Adults with high pain catastrophizing (back pain: n = 29, healthy: n = 7) and low pain catastrophizing (back pain: n = 20, healthy: n = 11), performed 10 repetitions of a lifting task. Electromyography data of rectus abdominis, erector spinae and external oblique muscles were collected, bilaterally. Co-contraction indices were determined for rectus abdominis/erector spinae and external oblique/erector spinae pairings, bilaterally. Pain catastrophizing was measured using the pain catastrophizing scale and task-specific fear using the Photograph series of daily activities scale. Three-way mixed ANOVAs tested the effects of group (back pain vs. healthy), pain catastrophizing (high vs. low), lifting phase (lifting vs. replacing) and their interactions.
Results: There were no main effects of pain catastrophizing, lifting phase, nor any interactions (p > 0.05). Group effects revealed greater co-contraction for bilateral erector spinae/rectus abdominis pairings (but not erector spinae-external oblique pairings) in people with back pain, compared to healthy participants, independent of pain catastrophizing and lifting phase (p < 0.05). Spearman correlations associated greater task-specific fear and greater erector spinae-left external oblique co-contraction, only in people with back pain (p < 0.05).
Conclusions: Greater co-contraction in the back pain group occurred independent of pain catastrophizing, as measured with a general questionnaire. A task-specific measure of threat may be more sensitive to detecting relationships between threat and co-contraction.
Significance statement: This work contributes evidence that people with back pain commonly exhibit trunk co-contraction when lifting. The lack of a relationship between pain catastrophizing and trunk co-contraction, however, challenges evidence linking psychological factors and guarded motor behaviour in this group. Together, this suggests that other factors may be stronger determinants of co-contraction in people with LBP or that a general construct like pain catastrophizing may not accurately represent this relationship.
Introduction: This study examines the effects of a Mindfulness-Based Stress Reduction (MBSR) program on psychological measures and attentional patterns to pain stimuli, using eye-tracking methods, in individuals with chronic pain.
Method: Thirty-two participants with chronic pain and no prior mindfulness experience were randomly assigned to an experimental group or a waiting list group. Both groups completed self-report measures of symptoms, well-being, and an attentional disengagement task using emotional faces as stimuli. Assessments were conducted at two points: before and after the intervention for the experimental group, with the waiting list group serving as a control.
Results: Before the MBSR program, chronic pain participants exhibited significant attentional biases towards pain-related stimuli during early attentional stages. Following the program, significant improvements were observed in depression, anxiety, stress, pain acceptance, overall well-being, and life satisfaction. However, it had a limited impact on attentional patterns, with only a significant increase in gaze duration across all stimuli.
Discussion: Despite the MBSR program's success in reducing symptoms associated with chronic pain, the lack of broader attentional improvements raises questions about the mechanisms responsible for psychological improvements.
Significance statement: This study pioneers the use of eye-tracking to examine how MBSR influences attention in chronic back pain. While the program improved psychological well-being, it did not generally alter attentional patterns, except for an increased ability to maintain attention across stimuli. We discuss whether this attentional change could be associated with the increased acceptance observed in the MBSR program.
Background and objective: In the presence of pain, whether clinical or experimentally induced, individuals commonly show impairments in the control of muscle force (commonly known as force steadiness). In this systematic review and meta-analysis, we synthesized the available evidence on the influence of clinical and experimental pain on force steadiness.
Databases and data treatment: MEDLINE, EMBASE, PubMed, CINAHL Plus and Web of Science databases were searched from their inception to 19 December 2023, using MeSH terms and pre-selected keywords related to pain and force steadiness. Two independent reviewers screened studies for inclusion and assessed their methodological quality using a modified Newcastle-Ottawa risk of bias tool.
Results: In total, 32 studies (19 clinical pain and 13 experimental pain) were included. Meta-analyses revealed reduced force steadiness in the presence of clinical pain as measured by the coefficient of variation (CoV) and standard deviation (SD) of force (standardized mean difference; SMD = 0.80, 95% CI = 0.31-1.28 and SMD = 0.61, 95% CI = 0.11-1.11). These findings were supported by moderate and low strength of evidence respectively. In the presence of experimental pain, meta-analyses revealed reductions in force steadiness when measured by the CoV of force but not by the SD of force (SMD = 0.50, 95% CI = 0.01-0.99; and SMD = 0.44, 95% CI = -0.04 to 0.92), each supported by very low strength of evidence.
Conclusions: This work demonstrates that pain, particularly clinical pain, impairs force steadiness. Such impairments likely have clinical relevance and could become targets for treatment when managing people experiencing musculoskeletal pain.
Significance statement: This systematic review and meta-analyses enhances our understanding of motor impairments observed in people experiencing musculoskeletal pain. It underscores the significance of incorporating force steadiness assessment when managing individuals experiencing musculoskeletal pain. Additionally, it suggests that future research should explore the potential benefits of force steadiness training in alleviating patients' symptoms and enhancing their functional performance. This could potentially lead to the development of innovative therapeutic approaches for individuals suffering from musculoskeletal pain.