The Journal of Pain

BackgroundPersistent Spinal Pain Syndrome (PSPS) type II represents a challenging clinical entity with limited therapeutic options. Various spinal cord stimulation (SCS) modalities have emerged as potential treatments, but their comparative effectiveness remains unclear. ObjectiveOur goal in this paper is to systematically evaluate and compare the efficacy of different SCS modalities in patients with PSPS type II through meta-analysis of available randomized controlled trials. Evidence ReviewWe conducted a systematic review following PRISMA guidelines, searching major databases for randomized controlled trials evaluating SCS modalities in PSPS type II patients until the end of May 2025(search updated on October 3rd). Primary outcomes included pain intensity (VAS) and functional disability (ODI) at 6 and 12 months. Subgroup analyses compared tonic versus burst stimulation and high-frequency versus low-frequency SCS. FindingsNine randomized controlled trials were included, encompassing 565 patients across different SCS modalities. For the primary outcome of clinically meaningful pain relief ([&ge;]50% reduction), pooled analysis demonstrated that 45% (95% CI: 18-75%, I{superscript 2} = 92.2%) of patients achieved this threshold for back pain and 55% (95% CI: 45-65%, I{superscript 2} = 0%) for leg pain. Subgroup analysis revealed significant differences in back pain responder rates by stimulation modality: High-frequency SCS demonstrated responder rates of 92% (95% CI: 79-98%) versus 28% (95% CI: 13-49%) for conventional frequencies (p < 0.001). For leg pain, no significant difference was observed between tonic (51%, 95% CI: 37-65%) and burst stimulation (60%, 95% CI: 45-74%, p = 0.36) and mean VAS scores demonstrated significantly lower pain with high-frequency SCS (13.30, 95% CI: 8.82-17.78) compared to conventional frequency (28.42, 95% CI: 24.02-32.88, p<0.0001). For back pain, mean VAS scores decreased from a baseline of 73.03 to 41.67 (95% CI: 36.12-47.22, I{superscript 2}=22.8%) at 6 months and remained stable at 35.66 (95% CI: 25.39-45.93, I{superscript 2}=75.0%) at 12 months. Leg pain showed more pronounced improvement, with VAS scores declining from a baseline of 61.81 to 23.75 (95% CI: 17.69-29.81, I{superscript 2}=78.8%) at 6 months and 29.16 (95% CI: 24.81-33.52, I{superscript 2}=0%) at 12 months). Meta-regression identified longer pain duration and older age as positive predictors of response, while higher baseline leg pain predicted lower responder rates. Serious adverse events occurred in 10%, with a 16% revision surgery rate. Only two studies demonstrated a low risk of bias across all domains. ConclusionsCurrent evidence demonstrates that various SCS modalities provide clinically meaningful pain relief in PSPS type II patients, with approximately half achieving [&ge;]50% pain reduction. High-frequency SCS shows significantly superior responder rates for back pain compared to conventional tonic stimulation, while burst stimulation yields significantly superior reductions in continuous pain intensity metrics. However, the limited number of studies, substantial heterogeneity, and lack of head-to-head comparisons prevent definitive recommendations regarding optimal stimulation parameters. Future large-scale randomized trials with standardized protocols and responder-based outcomes are needed to establish evidence-based treatment algorithms for PSPS type II patients.

Chronic pain (CP) can profoundly strain family systems, yet few population studies have explored CP with high impact on families. We used 2023 National Health Interview Survey Data (n=29,522) to characterize CP with high impact on families of U.S. adults. Findings are: (1) the prevalence of CP with high impact on families (HICP-Family) is 4.4% in U.S. adults and 18.1% in U.S. adults with CP; (2) HICP-Family is almost exclusively reported by those who have high impact chronic pain (HICP) that limits their individual functioning in life and work; (3) yet, among those with HICP, not all (46.3%) report HICP-Family; (4) HICP-Family can feasibly be modeled as a latter transition stage in a tiered cascade of advancing CP-associated impacts; (5) there is a strong association between clinically significant mental health symptoms and HICP-Family; HICP-Family is six times more prevalent among those who screen positive for moderate-to-severe anxiety or depression symptoms. Families highly impacted by CP may not be adequately resourced for adaptive functional resilience. HICP-Family may form an underappreciated barrier to achieving optimal pain and mental health outcomes for people with HICP. Further, without intervention, members of families highly impacted by CP may face heightened susceptibility to onset of suboptimal pain and mental health trajectories of their own. The need to develop effective supports and promote adaptive resilience in families highly impacted by CP is clear. Clinical tools to support person-centered assessment of family and relational functioning, effective family-level interventions, and innovative models of care are needed. IN BRIEFEstablishes prevalence of chronic pain with high impact on families (HICP-Family); situates HICP-Family within emerging pain research frameworks.

Dysfunctioning of stress systems, i.e., the autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis, has been implicated in chronic pain. However, the exact interplay between (re)activity and recovery of stress and pain systems in chronic pain remains unclear. A systematic review and meta-analysis was pre-registered on PROSPERO (CRD42024495934). Six databases were searched to identify relevant literature. Risk of bias (RoB) was evaluated with the Newcastle-Ottawa Scale, and certainty of evidence (CoE) with GRADE. Clusters of interactions between physiological markers of stress and experimental outcomes of pain were formed based on the timing of the stress measurements. Fifty-two studies (5 cross-sectional, 47 case-control; n = 2,657) were included and scored on average 9/12 (range: 2-11) on RoB. Overall CoE was very low to moderate. Qualitative analyses showed significant correlations between lower mean arterial pressure and higher pain sensitivity at baseline in individuals with chronic primary pain, which was supported by a meta-analysis. Furthermore, meta-analyses showed that higher pain sensitivity was associated with higher cortisol levels at baseline, lower high-frequency heart rate variability during recovery, and higher heart rate at multiple timepoints of the stress system response. Other associations did not yield significance. Taken together, these findings suggest that dysfunction of the ANS and HPA axis is linked to heightened pain sensitivity in chronic primary pain populations. However, the level of evidence remains low due to methodological heterogeneity, highlighting the need for studies combining stress markers and pain measures to provide insights into underlying stress-pain mechanisms. HIGHLIGHTS- Sympathetic cardiovascular dominance appears to be associated with enhanced pain sensitivity in chronic primary pain - A dysregulation in baroreflex activity might be present in chronic primary pain - HPA axis dysfunctioning seems to be related to enhanced pain sensitivity in chronic primary pain - Need for more standardized and comprehensive mapping of stress-pain interactions to unravel underlying mechanisms

BackgroundFor individuals with neck pain (NP) the type of health care provider (HCP) initially contacted and subsequent services used are less well understood than for low back pain (LBP). The purpose of this retrospective observational study of administrative data was to examine the association between type of HCP initially contacted by individuals with NP, service utilization, and total episode cost. MethodsA US national sample of NP episodes completed in 2017-2019 was analyzed. Separate analyses of a combined surgical and non-surgical (pooled) sample and a non-surgical sample were performed. Seventeen types of HCP initially contacted by an individual with NP was the primary independent variable. Dependent measures included rate and timing of use of fourteen types of health care services and total episode cost. A mixed effects model applied to pooled and non-surgical samples was used to test the association between initial contact HCP, total episode cost and rate of prescription opioid and NSAID use for NP. ResultsThe study included 323,348 continuously insured individuals aged 18 years and older with 390,992 complete episodes of NP involving 321,538 HCPs and incurring $472,399,064 in expenditures. 53.0% of episodes had initial contact with a primary care or specialist HCP, with these episodes associated with higher rates of imaging, pharmaceutical, and interventional services. 40.4% of episodes had initial contact with a non-prescribing HCP, with these episodes associated with higher rates of non-pharmaceutical services. Chiropractors (DC) were the most common type of HCP initially contacted (38.5% of episodes) and were associated with the lowest adjusted total episode cost. Results were consistent for individuals experiencing single or multiple episodes during the study period. ConclusionsThis study of a large US cohort of commercially insured individuals with NP helps fill a knowledge gap regarding NP care pathway attributes. Like LBP, the treatment of NP is highly variable with the initial HCP selected by an individual with NP associated with differences in services received and episode cost. Initial contact with a non-prescribing HCP was associated with lower rates of imaging, pharmacology, and interventional services.

BackgroundChronic pain is an ill-defined disease with complex biopsychosocial aspects, posing treatment challenges. We hypothesize that treatment failure results, at least partly, from limited understanding of diverse patient subgroups. We aim to identify subgroups through psychometric data, allowing for more tailored interventions. MethodsFor this retrospective cohort study, we extracted patient-reported data from two Dutch tertiary multidisciplinary outpatient pain clinics (2018-2023) for unsupervised hierarchical clustering. Clusters were defined by anxiety, depression, pain catastrophizing, and kinesiophobia. Sociodemographics, pain characteristics, diagnosis, lifestyle, health-related quality of life (HRQoL) and treatment efficacy were compared among clusters. A prediction model was built utilizing a minimum set of questions to reliably assess cluster allocation. ResultsAmong 5,454 patients with chronic pain, three clusters emerged. Cluster 1 (n=750) was characterized by high psychological burden, low HRQoL, lower educational levels and employment rates, and more smoking. Cluster 2 (n=1,795) showed low psychological burden, intermediate HRQoL, higher educational levels and employment rates, and more alcohol consumption. Cluster 3 (n=2,909) showed intermediate features. Pain reduction following treatment was least in cluster 1 (28.6% after capsaicin patch, 18.2% after multidisciplinary treatment), compared to >50% in clusters 2 and 3. A model incorporating 15 psychometric questions reliably predicted cluster allocation. In conclusion, our study identifies distinct chronic pain patient clusters through 15 psychometric questions, revealing one cluster with notably poorer response to conventional treatment. Our prediction model may help clinicians improve treatment by allowing patient-subgroup targeted therapy according to cluster allocation. In briefHierarchical clustering of chronic pain patients revealed three clusters based on pain experience and psychological welfare, with diverse sociodemographics and treatment effects suggesting potential for tailored interventions.

BackgroundFor individuals with low back pain (LBP), in the absence of serious pathology clinical practice guidelines (CPG) recommend a stepped approach to management with first-line emphasis on natural history, self-care, and non-pharmaceutical therapies. For individuals with non-surgical LBP initially contacting a chiropractor (DC), physical therapist (PT), or licensed acupuncturist (LAc), the purpose of this retrospective cohort study was to examine the dose response association between the number of visits of chiropractic manipulative therapy (CMT), active care (AC), manual therapy (MT), or acupuncture, exposure to second- and third-line services, and total episode cost. MethodsA national sample of individuals with a single episode of non-surgical LBP occurring in 2017-2019 was analyzed using episode of care as the unit of analysis. The primary independent variables were initial contact with either a DC, PT, or LAc, and the number of visits of CMT, AC, MT, or acupuncture. Dependent measures included rate and timing of use of 13 types of health care services and total episode cost. Results132,199 continuously insured individuals aged 18 years and older initially contacted 21,336 different DCs, 2,734 PTs and 1,339 LAcs for a single episode of non-surgical LBP. These individuals were associated with $62,185,930 in expenditures. The most common number of visits was 1 to 3 - CMT (48.2% of episodes), AC (29.7%), MT (32.1%), and acupuncture (27.0%). For each service, 1 to 3 visits was associated with the lowest rate of exposure to second- and third-line services although rate differences between visit dose categories were generally not significant or clinically. Episode total cost and duration increased significantly with increasing number of visits. CMT was associated with lowest median total episode cost at each level of visit utilization. ConclusionsFor non-surgical LBP episodes initially contacting a DC, PT or LAc, 1 to 3 visits of CMT, AC, MT, or acupuncture was the most common level of utilization, associated with the lowest exposure to second- and third-line services and lowest total episode cost. Among, CMT, AC, MT, and acupuncture, CMT was associated with the lowest total episode cost at each level of utilization. A higher number of visits of CMT, AC, MT or acupuncture was associated with significantly higher total cost, without meaningful impact on exposure to second- or third-line services. Unmeasured clinical benefits may be associated with higher visit counts and warrants further study.

We performed the first systematic review and meta-analysis of the prevalence of pain with neuropathic characteristics using Bayesian methods to correct prevalence estimates for the use of screening tools with imperfect sensitivity and specificity (CRD42023416845). We searched major databases for national or regional epidemiological studies that reported the prevalence of pain with neuropathic characteristics, as identified by the PainDETECT, S-LANSS, or DN4-interview. Of the 1,251 unique records retrieved, 8 were finally extracted. The uncorrected (apparent) prevalence data were pooled using a random-effects meta-analysis for proportions. The corrected (true) prevalence was estimated using Bayesian models incorporating sensitivity and specificity distributions under non-informative [beta(1,1)] and informative priors [beta(4.389, 29.522); based on apparent prevalence]. Using the mean values from Bayesian credible intervals, a pooled estimate of true prevalence was generated using a random-effects model. The pooled estimate for the apparent prevalence was 10.6% (95% CI: 8.5; 12.9). The pooled estimate for true prevalence was 4.9% (95% CI: 3.8; 6.1) using informative priors, and 2.3% (95% CI: 1.5; 3.2) using non-informative priors. The use of imperfect screening tools may have overestimated the prevalence of neuropathic pain. PerspectiveThe prevalence of neuropathic pain may be lower than previously estimated. A lower prevalence should not be equated with reduced societal or clinical significance, but it may have implications for healthcare resource allocation and research funding policies for neuropathic pain.

The concept nociplastic pain has been developed for patients in whom clinical and psychophysical findings suggest a predominant central sensitization type of pain that is not fully explained as nociceptive or neuropathic. Here we tested, how well the recently published grading system differentiates between chronic primary pain or chronic secondary pain conditions. We recruited patients with Fibromyalgia (FMS, 41), Complex Regional Pain Syndrome (CRPS, 11), Osteoarthritis (OA, 21) or Peripheral Nerve Injury (PNI, 8). We used clinical history, pain drawings, Quantitative Sensory Testing (QST) and questionnaires to classify patients pains as possibly or probably nociplastic in nature. All FMS and CRPS patients exhibited widespread or regional pain that was not explainable by nociceptive nor neuropathic mechanisms. Widespread pain in 12 OA patients was fully explained as nociceptive and regional pain in 4 PNI patients as neuropathic in all but one in each group. QST provided evidence for hypersensitivity in 9/11 CRPS patients but only 27/41 FMS patients (possible nociplastic pain). 82% of the CRPS patients but only 54% of FMS patients reported a history of hypersensitivity and mental comorbidities (probable nociplastic pain). We suggest that clinical examination of hypersensitivity should be done in more than one region and that adding a high tender point count as evidence for hypersensitivity phenomena may be useful. Further we suggest to switch the sequence of steps so that self-reported hypersensitivity and comorbidities come before clinical examination of hypersensitivity; Since the nociplastic pain concept calls for brainstem and cortical plasticity we discuss in detail potential measurement strategies.

QuestionIs a heatwrap combined with exercise more effective in improving symptoms and functional outcomes on short- mid- and long-term than either a heatwrap alone or a sham heatwrap in acute low back pain? DesignA multi-arm randomised controlled trial. ParticipantsAdults aged 18 to 65 years with a new episode of low back pain (defined as pain for six weeks or less with no low back pain in the three months preceding the current episode). InterventionParticipants were randomly assigned to one of three groups: heatwrap plus exercise (n=34), heatwrap alone (n=33) or sham heatwrap (n=32). All participants were asked to wear the heatwrap eight hours per day for seven days. The exercise group had to perform exercises 30 minutes per day for five days. All participants received evidence-based advice for the management of their pain. Outcome measuresOur primary outcome was pain-related disability at one week measured with the Oswestry Disability Index. Our secondary outcomes were pain intensity, pain-related fear of movement, self-efficacy, pain catastrophizing and perception of change. Outcomes were measured at baseline and at 1, 4, 12, 26 and 52 weeks. Data analysisWe used linear mixed models (LMMs) to compare intervention efficacy on all outcomes at all time-points with intention-to-treat analyses, testing the Group x Time interaction. ResultsThe analysis included 99 participants. The results for pain-related disability showed no Group x Time interaction (F=0.467; p=0.910), but a statistically significant time effect was observed (F=39.843; p<0.001) as scores decreased for all groups at one week, with an estimated mean difference of -7.8 (95% CI -9.7 to -5.9). All outcomes showed a time effect at all time-points. ConclusionA combination of heatwrap and exercise did not provide a superior effect on symptoms and functional outcomes on short-, mid and long-term when compared to a heatwrap alone and a sham heatwrap in adults with acute low back pain. Future guidelines should consider these results to formulate recommendations for acute LBP. Trial registration: ClinicalTrials.gov Identifier: NCT03986047

BackgroundLow back pain (LBP) is prevalent, management benefits from high-quality clinical practice guidelines, and yet LBP is a common source of low value care. The purpose of this retrospective cohort study was to examine the association between the type of initial contact health care provider (HCP), service utilization, and total episode cost for the management of LBP. MethodsEpisode of care was used to analyze a US national sample of LBP episodes completed in 2017-2019. A combined surgical and non-surgical (pooled) sample and a non-surgical sample were separately analyzed. The primary independent variable was the type of the initial contact HCP. Dependent measures included rate and timing of use of 14 types of health care services and total episode cost. The association between initial contact HCP, total episode cost and rate of prescription opioid and NSAID use was tested using a mixed effects model. ResultsThe study included 616,766 continuously insured individuals aged 18 years and older with 756,631 episodes of LBP involving 386,795 HCPs and incurring $1,010,495,291 in expenditures. A primary care or specialist HCP was initially contacted in 62.0% of episodes, with these episodes associated with early use of low-value services such as imaging, pharmacologic, and interventional services. A non-prescribing HCP was initially contacted in 32.5% of episodes with these episodes associated with early use of guideline recommended first line services. Each type of HCP emphasized different initial services with little indication of a stepped approach to managing LBP. Following adjustment for covariates chiropractors were associated with the lowest total episode cost. As an observational study of associations, numerous confounders may have impacted results. ConclusionsAn individual with LBP has different experiences based on the type of HCP initially contacted. Initial contact with primary care or specialist HCPs is associated with second- and third-line services provided before first line services, with little indication of a guideline recommended stepped approach to managing LBP. Increasing the likelihood of guideline- concordant, high-value care for LBP may require systemic changes to the health care delivery system. In the absence of red flags these changes may include increasing the proportion of individuals receiving early non-pharmacological treatment, either through improving direct access to non-prescribing HCPs or increasing timely referrals from primary care and specialist health care providers.

Sex related differences, without taking gender into account, in chronic pain have been widely researched over the past few decades in predominantly cisgender and heterosexual populations. Historically, chronic pain conditions have a higher incidence and prevalence in cisgender women, including but not limited to fibromyalgia, irritable bowel syndrome, and migraine. The goal of the present study was to identify and characterize the presence and characteristics of chronic pain in SM and GM persons using data from The PRIDE Study, which is the first large-scale, long-term national cohort health study of people who identify as lesbian, gay, bisexual, transgender, queer, or as another sexual or gender minority person. A total of 6189 adult participants completed The PRIDE Study 2022 Annual Questionnaire at the time of data analysis. A total of 2462 participants reported no chronic pain, leaving 2935 participants who reported experiencing chronic pain. The findings from this study highlight that chronic pain is present to a significant degree in sexual and gender minority adults who participated in The PRIDE Study with chronic spine pain being the most common location/region of pain. Notably, more than one-third of non-binary persons, transgender men, and people who selected another gender experienced chronic widespread pain, defined by having 3 or more total regions of chronic pain. The lowest prevalence of chronic widespread pain was among transgender women and cisgender men. When considering sexual orientation, the highest prevalence of widespread pain was in participants who selected another sexual orientation, followed by queer and asexual, demisexual, gray ace, with the lowest prevalence of chronic widespread pain being in those who identify as straight or heterosexual, bisexual, pansexual, gay, and lesbian. Future studies are planned to elucidate how a variety of biopsychosocial mechanisms may influence chronic pain in sexual and gender minority persons.

Background and objectivesObesity is one of the most prevalent comorbidities associated with chronic pain, the experience of which can severely interfere with activities of daily living and increase the utilization of clinical resources. Obesity is also a risk factor for increased pain severity (pain intensity) and pain interference (pain related disability). We hypothesize that a higher level of obesity, as measured by body mass index (BMI), would be associated with increased levels of pain severity and interference in a population of chronic pain clinic patients. MethodsParticipant data was pulled from a multi-site chronic pain outpatient database from 7/8/2011 to 10/17/2016. The Brief Pain Inventory (BPI), opioid prescriptions, and basic demographic information were queried and we categorized participants into three different ordinal categories based on recorded BMI levels (underweight, normal and overweight, obese). Bivariate analyses were performed to compare pain outcomes by BMI and by other demographic/clinical patient characteristics. Multivariable linear regressions were constructed to model each of four pain severity scores in addition to total pain interference score. All models examined BMI as the primary predictor, controlling for age, receipt of a pain procedure within 45 days prior to the pain clinic encounter, opioid prescription within 45 days prior to the encounter, and diagnosis. The total pain interference model additionally included pain severity (as measured by worst pain in the past 24 hours) as a covariate. Results2509 patients were included in the study. The median BMI was 27 and the median age was 59 years. 77% of patients were diagnosed with musculoskeletal pain conditions. Bivariate tests revealed significant differences between BMI groups for all pain severity scores and for total pain interference score. On multivariable modelling controlling for age, pain procedure within 45 days prior to pain clinic encounter, opioid prescription with 45 days prior, and diagnosis, obese patients had significantly higher pain severity (as measured by worst, least, average, and current pain in the past 24 hours) as well as higher pain interference (as measured by the overall pain interference score) than normal weight and overweight patients. ConclusionIn our study of pain clinic patients, obesity was found to be associated with increased pain severity and pain interference. We believe that this relationship is multifactorial and bidirectional. Pain phyisicans should consider the impact of obesity when addressing pain management for patients.

BackgroundThe associations between the type of health care provider (HCP) initially contacted by an individual with low back pain (LBP), guideline concordance, and cost of care are well understood. Less is known about types of HCP that become involved after the initial HCP, particularly the last HCP seen. The purpose of this retrospective cohort study was to examine sequence patterns in the types of HCP involved in an episode of LBP, exposure to 13 types of services, and total cost. MethodsA US national sample of commercially insured individuals with a single episode of non-surgical LBP occurring in 2017-2019 was analyzed using episode of care unit of analysis. The primary independent variable was the type of initial contact HCP. Dependent measures included types of subsequent HCPs involved in an episode of LBP, rate of use of 13 types of health care services, and total cost. Results503,958 individuals aged 18 years and older initially contacted 196,522 different HCPs for an episode of non-surgical LBP. 30.2% of individuals saw a second HCP, 11.8% a third, 5.2% a fourth and 2.5% a fifth. Compared to primary care providers (PCP) (71.0% of episodes), when chiropractors (DC) were the initial contact HCP they were the most likely to be the only and last HCP seen (84.0% of episodes) (risk ratio 1.18, 95% confidence interval 1.18-1.19). DCs were also the most likely to be the last HCP seen when the second HCP in an episode (72.7%) (1.10, 1.09-1.12), the third HCP (67.7%) (1.10, 1.08-1.13), or the fourth HCP (61.6%) (1.13, 1.08-1.17). Physical therapists (PT), while less likely than PCPs to be the only and last HCP seen (60.0%) (0.84, 0.83-0.86), were more likely than PCPs to be the last HCP when the second (70.9%) (1.08, 1.06-1.09), third (63.2%) (1.03, 1.00-1.06), or fourth HCP (60.7%) (1.11, 1.06-1.16) seen during an episode. PTs were the only type of HCP involved in more episodes as the second HCP (7,344) than as the initial HCP (5,114). ConclusionsDCs are the most likely to be the last HCP seen for an episode of non-surgical LBP. PTs are as likely as DCs to be the last HCP seen except when initially contacted by an individual with LBP. There are numerous potential confounders and limitations to consider when interpreting this novel finding.

Objectivesthis review aimed to investigate the presence of signs of central sensitization in patients with musculoskeletal disorders and associated chronic comorbidities. Methodswe conducted a systematic review (prespecified protocol CRD42021228970). Two authors independently searched for primary studies published between 2000 and 2021 in Web of Science and PubMed databases. We searched for studies that investigate the presence of signs of central sensitization in patients with musculoskeletal disorder or migraine and a chronic comorbidity. Two authors independently evaluated the methodological quality of the included studies using the "The Joanna Briggs Institute Critical Appraisal tools". When studies were judged homogenous enough, we performed a random effect meta-analysis. Resultswe included 14 observational studies. Overall, patients with musculoskeletal disorders or migraine with an associated comorbidity showed more signs of central sensitization compared with healthy subjects. The quantitative analysis showed that patients with temporomandibular disorders and chronic comorbidities, compared to patients with temporomandibular disorders without comorbidites, have a decreased pressure pain thresholds measured in the masseter area [SMD: -0.52; CI 95%: - 1.02 to -0.03; I2: 67%] and in the trapezius area [SMD: -0.55; CI 95%: -0.96 to -0.14; I2: 0%]. Patients with migraine, chronic low back pain or rheumatoid arthritis and associated fibromyalgia present more signs of central sensitization, measured in different modalities, than subjects without comorbidity. Conclusionswe demonstrated that, in general, patients with musculoskeletal disorders and an associated comorbidity showed an increased incidence of signs of central sensitization compared to healthy subjects and patients with musculoskeletal disorders without comorbities.

IntroductionChronic pain is often unrecognized and/or undertreated, and as a result has significant impact on functional abilities, quality of life, societal participation and health care utilization. Medications remain a mainstay of treatment, but selection for any given patient remains a challenge when trying to predict efficacy and/or side effects. There is interest to see whether genetic analysis of how a given drug is processed for a patient can help with rational drug choices. This appears to have some early support in cardiac, psychiatric and acute pain studies. We studied whether genetic analysis of drug processing using the Pillcheck program could have helped in choosing the appropriate medications in a cohort of patients suffering from chronic pain. To our knowledge this type of study has not been completed in this environment and/or patient population. MethodsWe retrospectively studied a 31 patient cohort seen in the Canadian Forces Health Services Unit (Ottawa) Physiatry clinic. All patients suffered from a diagnosed chronic pain condition, completed the Pillcheck genetic drug processing analysis and filled-in questionnaires looking at efficacy and side effects of the drugs. We analyzed the correlation between the Pillcheck predictions and participants self-reported treatment efficacy and tolerability. The goal was to explore the clinical utility of Pillcheck results in guiding prescriptions for chronic pain patients. Results31 patients returned completed questionnaires and had samples taken. Forty eight percent of the participants were actively treated with one of the study pain medications, and 84% had been taking at least one of these medications and discontinued. Pillcheck scores did not correlate with self-reported efficacy of any of the medications, nor did it correlate with self-reported side effects. Furthermore, active medications were more likely to receive a score indicating caution should be exerted, than were medications which had been discontinued. DiscussionIn a small cohort of pain patients with comorbid psychiatric disorders, genetic profiling using Pillcheck did not seem to correlate with reported benefit or side effect profile of commonly prescribed pain medications. Furthermore, discontinued medications were no more likely to be marked as warranting caution than did actively used medications. ConclusionRetrospectively using pharmacogenetics to guide medication selection in Canadian Forces members with chronic pain did not correlate with response or side effects. A larger prospective controlled study, measuring numerous clinical and non- clinical outcomes would be worthwhile in the future before widespread adoption for patients living with chronic pain.

Countries across the world imposed lockdown restrictions during the COVID-19 pandemic. It has been proposed that lockdown conditions disproportionately impact those living with chronic pain, requiring adaptation to treatment and care strategies. We investigated how lockdown restrictions in the United Kingdom impacted individuals with chronic pain (N = 431) relative to a healthy control group (N = 88) using an online survey. In accordance with the fear-avoidance model, we hypothesised increases in perceived pain and psychological distress that would be mediated by pain catastrophizing. Survey questions answered during the lockdown period, probing patients self-perceived changes retrospectively, revealed that people with chronic pain perceived increases in their pain severity compared to before lockdown. They were also more adversely affected by lockdown compared to pain-free individuals, demonstrating greater increases in anxiety and depressed mood, increased loneliness and reduced levels of physical exercise. Pain catastrophizing was found to be an important factor in predicting the extent of self-perceived increases in pain, and accounted for the relationship between decreased mood and pain. Perceived decreases in levels of physical exercise also independently predicted perceptions of increased pain. Interestingly, actual changes in pain symptoms (measured at two time points at pre- and post-lockdown in a subgroup, N = 85) did not change significantly on average, but those reporting increases also demonstrated greater baseline levels of pain catastrophizing. Overall, the findings suggest that remote pain management provision to target reduction of catastrophizing and increases to physical activity could be beneficial for chronic pain patients in overcoming the adverse effects of lockdown.

BackgroundDespite known deleterious consequences associated with long-term opioid use, many individuals with chronic pain assert opioid benefits and advocate for continued opioid use. However, relative to non-opioid using chronic pain patients, opioid-using patients typically report greater pain severity and depression. Moreover, there appears to be no significant association between pain severity or interference and perceived opioid benefit among chronic pain patients. Thus, pain reduction itself might not directly relate to patients perceptions of opioid benefit. Given extensive prior research revealing significant overlaps between pain and affect, it is prudent to examine contributions of affective disturbances--alongside pain-related factors--to perceived opioid benefits. In the present study, we examined the hierarchical contributions of pain interference and positive affect in predicting self-reported opioid benefit. We hypothesized that positive affect combined with pain interference would best predict opioid benefit. MethodsWe examined multisite, cross-sectional data collected from females with fibromyalgia who were using opioids long-term (n = 40) and who were not regularly using opioids but had used them acutely (< 30 days) at least once previously (n = 25). Patients completed a set of questionnaires, including the Positive and Negative Affect Schedule, the Brief Pain Inventory, and a novel measure querying perceived opioid benefit on a 0-10 Likert scale (0 = not at all, 10 = completely). We examined relationships between pain interference, positive affect, and patient-reported opioid benefit using logistic regression. ResultsAmong opioid-using patients, pain interference combined with positive affect was a better model for opioid benefit (AIC = 52.15) compared to pain interference alone (AIC = 57.80). However, among non-opioid using patients, pain interference alone was a better model for opioid benefit (AIC = 28.00) than pain interference combined with positive affect (AIC = 28.12). ConclusionsAmong patients using opioids long-term, affective factors may be primary drivers of perceived opioid benefit. Positive affect combined with pain interference modeled opioid benefit better than pain interference alone among opioid-using chronic pain patients, but not among non-opioid-using chronic pain patients. Importantly, post-hoc analyses examining the contributions of negative affect further validated the main findings; positive affect out-performed negative affect in all models. Thus, perceived opioid benefit may be a function of cumulative opioid-induced enhancements in positive affect. Based on these results, examination of factors besides pain reduction may be critical to understanding perceived opioid benefit among chronic pain patients; this understanding is essential for development of effective, opioid-sparing treatments. Key Points SummaryO_ST_ABSQuestionC_ST_ABSDoes the combination of pain and affect predict patient-reported (i.e., perceived) opioid benefit better than pain alone, and do these relationships differ between groups of opioid-using and non-opioid using individuals with chronic pain? FindingsCompared to pain interference alone, pain interference combined with positive affect was a better model of perceived opioid benefit among opioid-using chronic pain patients, but not among non-opioid using chronic pain patients, who had used opioids acutely at least once previously. MeaningAmong patients with chronic pain using opioid medications long-term, perceived opioid benefit appears to be a consequence of opioid-related enhancements in positive affect rather than pain reduction per se.

Complex Regional Pain Syndrome (CRPS) exhibits persistent disproportionate limb pain and hyperalgesia associated with neuroinflammatory and autonomic changes, typically after inciting limb injury. However, little is known about the progression of somatosensory changes over time. We reviewed cross-sectional studies employing standardised Quantitative Sensory Testing (QST) in accordance with the DFNS comprehensive somatosensory test protocol, stratified for CRPS duration. This study was registered with PROSPERO ID CRD42020216485. Reporting follows PRISMA guidelines. Databases searched were PubMed, Cochrane Library, Google Scholar, EMBASE, Web of Science and Scopus. Studies of adult patients with CRPS and QST according to the DFNS protocol were included. 1415 articles were screened and 23 studies meeting the inclusion criteria were included in quantitative analysis and narrative synthesis. Analysis was stratified by CRPS duration into an early ([&le;] 6 months), intermediate (6-12 months) and late (> 12 months) time window. Across all studies encompassing 2059 CRPS patients all somatosensory parameters deviated significantly from healthy subject profiles (all P < 0.001). All non-nociceptive detection parameters displayed a significant loss of sensitivity, while all nociceptive parameters as well as thermal and mechanical dysesthesias, i.e., paradoxical heat sensation and allodynia displayed a significant gain of sensitivity. Pressure pain threshold (PPT) showed the most drastic sensory gain with a large effect size (> 2 SD; Hedges g = 0.9) equivalent to more than half of CRPS patients exhibiting abnormal pressure hyperalgesia. Moreover, PPT significantly increased progressively with increasing CRPS duration (from 1.7 to 2.2 and 2.8 SD above normal). In late CRPS (> 12 months), additionally contralateral, mirror image test site sensory loss (P < 0.001) and pressure hyperalgesia (P < 0.001) became evident. Stratification for magnitude of pain did only modestly predict relevant differences in somatosensory profiles. Quantitative analysis of 23 cross-sectional QST studies in CRPS demonstrates pressure hyperalgesia as the signature CRPS sensory abnormality, distinguishing CRPS from neuropathic pain conditions. Further, pressure hyperalgesia exhibits a peculiar dramatic step progression between 4-12 months, without equivalent in other parameters. In late CRPS, somatosensory profiles become significantly abnormal at contralateral areas indicating loss of regionality. These findings have important implications for the classification of CRPS as a chronic primary pain condition, for understanding challenges to rehabilitative interventions, and for condition-subtyping.

Our response to threats, including pain, are believed to be learnt during our early interpersonal relationships, and can be measured through attachment style. Preliminary epidemiological evidence suggests that insecure attachment styles are more prevalent in those with chronic pain. Our aim was to determine the association between adult attachment style and chronic pain prevalence and burden in a South African population. A nationwide online survey determined adult attachment style (using The Experience in Close Relationships - Relationship Structures (ECR-RS) Questionnaire), prevalence of chronic pain and typically-associated psychological factors. In those with chronic pain, the association with attachment style and pain burden (pain sites, severity and interference, using the Brief Pain Inventory) was further determined. Results of the 2371 individuals were analyzed using multivariate generalized linear models. In our young (median age 23 years; IQR 20-28), well-educated and primarily female (74%) cohort with predominantly a middle-to-high socioeconomic status, we found a high prevalence of chronic pain (27%). All three insecure attachment styles were associated with increased chronic pain prevalence when compared to the secure attachment style (Dismissing: 31%, Odds ratio [95%CI] = 1.38 [1.02-1.85], p=0.037; Preoccupied: 42%, Odds ratio [95%CI] = 2.26 [1.62-3.13], p<0.001; Fearful: 49%, Odds ratio [95%CI] = 2.95 [2.03-4.29], p<0.001). Adult attachment style was not directly associated with the burden of chronic pain, because pain catastrophizing mediated this relationship. Adult attachment style was, however, directly associated with chronic pain prevalence, with more than double the chronic pain prevalence in the fearfully, compared to securely, attached individuals.

BackgroundNew-onset chronic musculoskeletal (MSK) pain (> 3 months duration) is one of the commonest persistent symptoms of Post-COVID syndrome (PCS). There is emerging evidence that the chronic MSK pain and associated symptoms in PCS have similarities to Fibromyalgia Syndrome (FMS). This study aimed to characterise PCS related new-onset chronic MSK pain and its overlap with Fibromyalgia Syndrome (FMS). MethodsPatients with new-onset chronic MSK pain following COVID-19 infection were enrolled and the nature of pain and associated symptoms captured using the C19-YRS (Yorkshire Rehabilitation Scale). FMS assessment was conducted as part of standard clinical examination using the American College of Rheumatology (ACR) 2010 criteria. Diagnosis of FMS was made when they meet the standard criteria of (1) Widespread Pain Index (WPI) [&ge;] 7 and Symptoms Severity (SS) score [&ge;] 5, or WPI is 3-6 and SS score [&ge;] 9, (2) symptoms have been present at a similar level for at least 3 months, and (3) the patient does not have a disorder that would otherwise explain the symptoms. ResultsEighteen patients, twelve of whom were female, with an average age of 49.6 (SD 11.8) years and a Body Mass Index of 31.7 (SD 8.6) were enrolled. The average duration of symptoms from COVID-19 infection to assessment was 27.9 (SD 6.97) months. The new-onset chronic pain was widespread, primarily manifesting as muscle pain. Thirteen (72.2%) patients met the diagnostic criteria for FMS, with an average WPI score of 8.8 and an average SS score of 8.2, indicating a high level of pain and significant adverse impact on their quality of life. ConclusionThe study found that 72.2% of the patients with new-onset chronic MSK pain following COVID-19 infection met the criteria for FMS. These findings support the hypothesis that FMS may develop as a long-term sequela of a viral infection, underscoring the need for further research into post-viral long-term conditions.