Volume 19, Issue 1

Background and aims Multidomain strategies (i.e. two or more strategies) for managing chronic pain are recommended to avoid excessive use of opioids while producing the best outcomes possible. The aims of this systematic review were to: 1) determine if patient-reported pain management is consistent with the use of multidomain strategies; and 2) identify the role of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) in patient-reported pain management. Methods Bibliographic databases, websites, and reference lists of included studies were searched to identify published articles reporting community-based surveys of pain self-management from January 1989 to June 2017 using controlled vocabulary (and synonyms): pain; self-care; self-management; self-treatment; and adult. Two independent reviewers screened studies and extracted data on subject demographics, pain characteristics, pain self-management strategies, and pain outcomes. Pain self-management strategies were organized according to our conceptual model. Included studies were assessed for risk of bias. Differences between the researchers were resolved by consensus. Results From the 3,235 unique records identified, 18 studies published between 2002 and 2017 from 10 countries were included. Twenty-two types of pharmacological strategies were identified (16 prescription, six non-prescription). NSAIDs (15 studies, range of use 10–72%) and opioids (12 studies, range of use 5–72%) were the most commonly reported prescription pharmacological strategies. Other prescription pharmacological strategies included analgesics, acetaminophen, anticonvulsants, antidepressants, anxiolytics, salicylates, β-blockers and calcium channel blockers, disease-modifying anti-rheumatic drugs and steroids, muscle relaxants, topical products, triptans, and others. Twenty-two types of non-pharmacological strategies were identified: four medical strategies (10 studies), 10 physical strategies (15 studies), four psychological strategies (12 studies), and four self-initiated strategies (15 studies). Medical strategies included consulting a medical practitioner, chiropractic, and surgery. Physical strategies included exercise, massage, hot and cold modalities, acupuncture, physical therapy, transcutaneous electrical nerve stimulation, activity modification or restriction, assistive devices, and altering body position/posture. Psychological strategies included relaxation, prayer or meditation, therapy, and rest/sleep. Self-initiated strategies included dietary or herbal supplements, dietary modifications, and complementary and alternative medicine. Overall, the number of strategies reported among the studies ranged from five to 28 (out of 44 identified strategies). Limited data on pain outcomes was reported in 15 studies, and included satisfaction with pain management strategies, pain interference on daily activities, adverse events, lost work or restricted activity days, emergency department visits, and disabilities. Conclusions A wide variety and large number of pharmacological and non-pharmacological strategies to manage chronic pain were reported, consistent with the use of multidomain strategies. High levels of use of both NSAIDs and opioids also were reported. Implications Comprehensive review and consultation with patients about their pain management strategies is likely needed for optimal outcomes. Additional research is needed to determine: how many, when, and why multidomain strategies are used; the relationship between opioid use, multidomain management strategies, and level of pain; how multidomain strategies relate to outcomes; and if adding strategies to a pain management plan increases the risk of adverse events or interactions, and increases an individuals pain management burden.

Background and aims The choice of testing site for quantitative sensory testing (QST) of pain sensitivity is important and previous studies have demonstrated patterns in pain sensitivity within discrete areas in different body regions. Some areas are characterized by a relatively high degree of spatial pain discrimination and recognizable patterns of pain referral, whilst others are not. The lumbar region is likely to have relatively low pain acuity and overlapping of pain referral. The current study was conducted to determine whether patterns of pain sensitivity (detection thresholds) could be identified in the lower back, whether differences in such patterns exist between different groups and whether such patterns could help identify a clinical source of pain and localized increased pain sensitivity. Methods Twenty-one patients with non-specific chronic low back pain and 21 healthy controls were tested for pressure and heat pain thresholds on 30 pre-defined locations over the mid and lower back. Topographical maps of mean pain thresholds and variability were produced, inspected visually and analyzed statistically. Between group differences in pain threshold were analyzed statistically as an indicator of widespread increased pain sensitivity. Evidence of segmental increased pain sensitivity was examined by group statistical comparison of mid-line lower range. Results A clear pattern of higher pain thresholds in the mid-line was evident in both groups and for both pain modalities. No discernible patterns were evident for variability within groups, but marked differences were seen between groups: variability for pressure pain thresholds appeared similar between groups, however for heat pain threshold, variability was uniformly low in the control group and uniformly high in the patient group. A highly significant ( p <0.0001) difference in pain thresholds for pressure and heat was found with patients exhibiting lower thresholds than controls. No between group difference was found for mid-line lower range for either modality ( p >0.05). Conclusions The current study supports previous findings of widespread, increased pain sensitivity in chronic non-specific low-back pain patients. It also indicates that there are discernible and similar topographical patterns of pain sensitivity in the dorsal area in both groups, but that this pattern is related to the lateral position of the test site and not the segmental level. Specific segments with increased pain sensitivity could not be identified in the patient group, which casts doubt on the utility of pressure and heat pain thresholds as indicators of the clinical source of spinal pain – at least in a population of chronic non-specific low-back pain. Implications In a cohort of chronic non-specific low-back pain patients and with the chosen methodology, topographical QST mapping in the lumbar region does not appear useful for identifying the spinal segment responsible for clinical pain, but it does demonstrate widespread group differences in pain sensitivity.

Background and aims As indicated by experimental studies, reports of pain intensity may depend on the examiner’s gender. Until now, it is unclear whether this is relevant in clinical routine. This study investigated prospectively whether the gender of assessor plays a role in patients’ pain reports and whether this role differs in male and female patients. Methods 165 patients (66.4 years±0.63; 118 males) scheduled for heart surgery were allocated consecutively to one examiner out of four students of both genders: two females and two males (aged 24.3 years±1.7). Therefore, the following study groups were defined: Group 1: female assessors-female patients, 2: female-male; 3: male-female, 4: male-male. Using a standardized analgesic scheme, patients were asked to rank their pain intensity on a numeric rating scale (NRS: 0–10), postoperatively. Statistics: Kruskal-Wallis, Mann-Whitney; p <0.05. Additionally, a qualitative literature review of the databases Medline and CENTRAL was performed focusing on experimental and clinical studies on experimenter gender bias. Due to the review, this prospective clinical study was designed to investigate whether patients after surgery report lower pain intensities when assessed by a female compared to a male assessor. Results Summarizing all patients, pain intensity on POD_1 was rated 4.0±2.4 on NRS and decreased on POD_2 to 3.0±2.1 [H(3)=37.941, p =0.000]. On average, pain intensity did not differ between males and females (NRS: 3.5 vs. 3.6). Only on the second postoperative day, more intense pain was reported in front of female assessors and less intense pain in front of male assessors (NRS: 3.4 vs. 2.4; p =0.000). A main effect for the four groups was seen ( p =0.003): male patients reported higher pain scores to female assessors (NRS: 3.5 vs. 2.3; p =0.000). Conclusions Together, contrary to the expectations, patients after cardiac surgery reported a higher pain intensity in front of a female and a lower pain intensity in front of a male assessor. In particular, female caregivers may heighten the reported pain intensity up to 1.2 NRS-points; this bias seems to be more relevant for male patients. Implications Therefore, despite some methodological weakness, our data suggest that attention should be paid to a rather small, but somehow significant and consistent examiner gender bias after cardiac surgery especially in male patients. Further clinical studies are needed to show the true extent of clinical relevance and exact mechanisms underlying these gender reporting bias.

Background and aims For some women, lumbopelvic pain (LPP) developed during pregnancy becomes a continuing post-partum problem. Increased understanding of potential prognostic factors is required. This study investigated whether active straight leg raise (ASLR), sleep dysfunction and pressure pain sensitivity during pregnancy are correlated with LPP intensity and quality, disability, and physical health-related quality of life (HRQoL) post-partum. Methods An exploratory, prospective cohort study design was used. Baseline factors of interest were: (1) ASLR, (2) Pittsburgh Sleep Quality Index, and (3) pressure pain thresholds (PPTs) collected from pregnant women from sites local and distal to the lumbopelvic area. Follow-up data collected 11–18 months post-partum ( n =29) were: (1) pain intensity score (numerical rating scale), (2) pain quality (McGill Pain Questionnaire), (3) disability (Pelvic Girdle Questionnaire), and (4) HRQoL (36-item Short Form Health Survey). Correlation analysis was performed. Results Greater difficulty with an ASLR during pregnancy correlated with lower post-partum physical HRQoL scores (r=−0.563, p =0.002). Likewise, reduced PPTs at the sacrum during pregnancy was correlated with a higher post-partum pain quality score (r=−0.384, p =0.040). Conclusions In this cohort, findings indicate that poor ASLR performance and localised pressure pain hypersensitivity at the pelvis during pregnancy are correlated with post-partum physical HRQoL and pain quality, respectively. Implications Pain sensitivity may contribute to the prognosis of women with LPP during pregnancy. These explorative findings may be important for designing larger prognostic studies and may assist in directing potential pain management in post-partum LPP.

Background and aims Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is challenging to live with, often accompanied by pervasive fatigue and pain, accompanied by decreased quality of life (QoL) as well as anxiety and/or depression. Associations between higher pain, lower QoL and higher anxiety and depression have been shown in patients with various chronic pain disorders. Few studies have however examined such associations in a sample of patients with ME/CFS. The aims of the current study were to examine the impact of pain levels and compare levels of pain, health related QoL, anxiety and depression between patients with ME/CFS and healthy controls. In addition, the study aimed and to examine these relationships within the patient group only. Methods This is a cross-sectional questionnaire based study comparing 87 well-diagnosed patients with ME/CFS with 94 healthy controls. The De Paul Symptom Questionnaire (DSQ), the Medical Outcomes Study Short-Form Surveys (SF-36) and the Hospital Anxiety and Depression Scale (HADS) were used to examine and compare pain, physical function, QoL, anxiety and depression in patients and healthy controls. Further the pain variables were divided into pain total, pain intensity and a pain frequency score for analyses of the above mentioned variables within the patient group only. Results Significantly higher levels of pain, anxiety and depression, and lower levels of QoL were found in the patient group compared with healthy controls. For the patient group alone, pain was significantly associated with lower QoL in terms of physical functioning, bodily pain, general health functioning, vitality and social functioning capacity. In this patient sample, only frequency of joint pain showed significant difference in psychological variables such as depression and anxiety – depression combined. Conclusions ME/CFS patients differ significantly from healthy controls in pain, health related QoL, anxiety and depression. Pain is significantly associated with reduced QoL and overall a lower level of functioning. The relation between pain and anxiety and depression appears less clear. Implications Pain is for many ME/CFS patients associated with reduced physical functioning and reduced QoL. A thorough pain assessment can therefore be essential for clinicians, and subsequent medical pain treatment combined with good pain coping skills may increase functioning level and QoL for these patients. The link between joint pain and psychological factors should also be focused in clinical practice in terms of mapping and counseling. Pain should be further examined to understand the importance it may have for functioning level as reduced function is a main criteria when diagnosing the patients.

Background and aims Among chronic pain patients who are referred to participation in a multimodal rehabilitation program (MMRP), pain catastrophizing and dysfunctional pain coping is common. In many cases it may have driven the patient to a range of unsuccessful searches for biomedical explanations and pain relief. Often these efforts have left patients feeling disappointed, hopeless and misunderstood. The MMRP process can be preceded by a multimodal investigation (MMI) where an important effort is to validate the patient to create a good alliance and begin a process of change towards acceptance of the pain. However, whether the MMI has such therapeutic effect is unclear. Using a repeated single case experimental design, the purpose of this study was to investigate the therapeutic effect of MMI by studying changes in patients’ experience of validation, alliance, acceptance of pain, coping, catastrophizing, and depression before and during the MMI process. Methods Participants were six chronic pain patients with high levels of pain catastrophizing (>25 on the Pain Catastrophizing Scale) and risk for long term disability (>105 on the Örebro Musculoskeletal Pain Screening Questionnaire) who were subjected to MMI before planned MMRP. For each patient, weekly self-report measures of validation, alliance and acceptance of pain were obtained during a 5–10-weeks baseline, before the MMI started. Subsequently, these measures were also obtained during a 6–8 weeks MMI process in order to enable comparative analyses. Additionally, pain coping, depression and pain catastrophizing were measured using standardized questionnaires before and after the MMI. Results Irrespective of experiences of validation and alliance before MMI, all six patients felt validated and experienced a good alliance during MMI. Acceptance of pain improved only in one patient during MMI. None of the patients showed clinically relevant improvement in pain coping, depression or catastrophizing after the MMI. Conclusions The patients did not change their acceptance and pain coping strategies despite of good alliance and experience of validation during the MMI process. Even if the design of this study precludes generalization to chronic pain patients in general, the results suggest that MMI may not have a therapeutic effect.

Background and aims The Fear-Avoidance Beliefs Questionnaire (FABQ) is the most widely used self-reported measure of fear-avoidance beliefs about work and physical activity in low back pain (LBP). However, there is no Hausa version for use in patients with LBP. This study aimed to translate, cross-culturally adapt, and test the psychometric properties of the Hausa version of the FABQ in patients with LBP. Methods The Hausa form of FABQ was developed using a forward-backward translation procedure according to recommended guidelines. The pre-final version of the questionnaire was pre-tested on 10 patients with acute LBP and 10 patients with chronic LBP. Psychometric testing was performed in 70 patients with acute LBP and 130 patients with chronic LBP. Reliability was assessed using internal consistency (Cronbach α) and test-retest reliability through intraclass correlation coefficient (ICC). Construct validity was assessed by exploratory factor analysis and divergent validity (Spearman rank correlation coefficient). Responsiveness was also investigated on 40 patients with chronic LBP. Results The Hausa version of the FABQ was successfully translated and proved to be well-understood. The internal consistency was adequate for the questionnaire (0.773) and its physical activity (0.816) and work (0.606) subscales. Test-retest reliability was excellent with an ICC value of 0.928 for the questionnaire and values of 0.901 and 0.863 for the physical activity and work subscales, respectively. Exploratory factor analysis yielded a three-factor structure in both acute and chronic LBP samples explaining 66.4% and 58.6% of the total variance, respectively. The first factor represents fear-avoidance beliefs due to work, the second factor represents fear-avoidance beliefs due to physical activity whereas the third factor represents the fear that pain aggravates due to work. Divergent validity showed moderate to weak correlation between the questionnaire and pain intensity (r=0.502), disability (r=0.415), lumbopelvic motion (r=0.00). The physical activity and work subscales weakly correlated (r=0.280). The effect size and standardized response mean were moderate to small with the work subscale having the lowest effect size (0.34) and standardized response mean (0.34) values. The MDC of the questionnaire was 5.4 points. The questionnaire had no ceiling or floor effects. Conclusions The FABQ was successfully translated into Hausa and cross-culturally adapted with acceptable psychometric properties similar to those of existing versions. The results suggest that the Hausa FABQ can be used to evaluate fear-avoidance beliefs about LBP in Hausa-speaking population for both clinical and research purposes.

Background and aims Almost 20% of the adult population suffers from chronic pain. Chronic pain may be linked to an elevated mortality; however, results from previous studies are inconsistent. Some studies find similar mortality levels in chronic pain patients and pain-free controls while other studies show elevated mortality levels among chronic pain patients, primarily with respect to cancer, diseases of the circulatory and respiratory systems, and suicide. These conflicting results are potentially due to different population samples and different operational definitions of chronic pain. Further research on overall and cause-specific mortality in patients with severe chronic pain is needed to inform clinical practice. The objective of this register-linkage study was to investigate whether patients with severe chronic pain referred to multidisciplinary pain treatment have higher cause-specific mortality rates than the general population. Methods In this register-linkage cohort study, data from 6,142 chronic pain patients (female: n =3,941, male: n =2,201, mean age: 48.2±14.2; range: 16–97 years) attending an interdisciplinary Pain Center in Odense, Denmark from 2005 to 2014 were linked to the Danish Register of Causes of Death. Age and gender standardized mortality ratios (SMRs) with their 95% confidence intervals (CI) were calculated and compared with those of the general population. Data from the general population was extracted from the Danish Register of Causes of Death, and Causes of death were classified according to national Classification of Disease (ICD-10). Results In all, 276 deaths (women: n =152, men: n =124) were observed among the chronic pain patients, and a six-fold higher overall mortality rate was found [SMR: 6.2 (95% CI: 5.5–7.0)] compared with the general population. Elevated cause-specific mortality rates were noted for chronic patients with respect to cancer and neoplasms [4.7 (95% CI: 3.7–5.9)], diseases of the circulatory system [5.7 (95% CI: 4.3–7.3)], diseases of the respiratory system [8.7 (95% CI: 6.2–11.9)], and suicide [7.3 (95% CI: 2.7–15.9)]. Conclusions The overall mortality rate of patients with severe chronic pain in this study was six-fold higher than the rate of the general population in this region. This was reflected in select specific causes of death (cancer and neoplasms, diseases of the circulatory system, diseases of the respiratory system, and suicide). The results are in agreement with previous studies and emphasize the need to understand which factors causally affect this increased mortality allowing for targeted interventions in similar chronic pain populations. Implications Potential reasons for the excess mortality should be adequately addressed by future studies in order to better target this in the management of these patients. The chronic pain population included in this study may have several comorbidities contributing to the increased mortality. To better address these aspects, complete medical profiles are needed in future studies. In addition, implementation of management strategies towards potential risk factors such as poor diet, low levels of physical activity, smoking, and high BMI as well as sleep deprivation and morphine use previously shown associated with having pain may reduce the excess mortality ratio.

Background and aims Pain is a common condition. However, only a minority of people experiencing pain develop a chronic pain problem. Factors such as somatization, pain self-efficacy and lack of psychological well-being affect the risk of pain chronicity and pain-related disability. However, research on protective pain-related psychological factors in populations without chronic pain is scarce. We aim to examine if pain self-efficacy attenuates the associations between pain and both anxiety and somatization in a community sample. Methods In a cross-sectional study, 211 participants from a community sample responded to measures of average pain over the last 3 months, anxiety, somatization, and pain self-efficacy. The possibility of moderation effects were tested with a series of regression analyses. Results The association between pain and anxiety was not moderated by pain self-efficacy. In contrast, pain self-efficacy moderated the relation of pain and somatization. The interaction explained 3% of the variance in somatization, in addition to the independent effects of pain and self-efficacy (F(1,207)=5.65, p <0.025). Among those in the bottom quartile of pain self-efficacy, the association between pain and somatization was moderate or strong (r=0.62, p <0.01), whereas for those in the top quartile the association was modest (r=0.11, p >0.05). Conclusions The results are partly consistent with the hypothesis that pain self-efficacy attenuates the associations between pain and pain chronification risk factors in a relatively healthy community sample. Should further preferably longitudinal studies replicate the findings, the role pain self-efficacy as a protective factor needs to be explicated in theoretical models of pain chronification. Implications The findings are consistent with the notion that clinicians should promote patient’s pain self-efficacy in acute and sub-acute pain conditions especially when the individual is prone to somatization. However, more prominent clinical implications require studies with longitudinal designs.

Background and aims Caring for children with chronic pain incurs burdens of cost and time for families. We aimed to describe variation in caregiver burden among parents of adolescents with chronic pain who responded to a nationally-representative survey. Our secondary aim was to identify child and parent characteristics associated with increased caregiver burden. Methods We used de-identified, publicly-available data from the 2016 National Survey of Children’s Health (NSCH), designed to be representative of non-institutionalized children in the United States. We analyzed data for households where an adolescent age 12–17 years old was reported by a parent to have chronic pain. Outcomes included the parent’s time spent on the child’s health needs, reduced labor force participation, and out-of-pocket medical costs. Results Data on 1,711 adolescents were analyzed. For adolescents with chronic pain, 15% of parents reported spending at least 1 h/week on their child’s health care, 14% reported cutting back on paid work, and 36% reported spending ≥$500 on their child’s health care in the past 12 months. Adolescents’ general health status and extent of specialized health care needs predicted increased caregiver burden across the three measures. Conversely, no consistent differences in caregiver burden were noted according to demographic or socioeconomic characteristics. Conclusions Among adolescents with chronic pain identified on a nationally-representative survey, parents frequently reported reducing work participation and incurring out-of-pocket expenses in providing health care for their child. Caregiver burdens increased with indicators of greater medical complexity (e.g. presence of comorbidities, need for specialized health care) and poorer overall adolescent health status. Implications We add a national-level perspective to studies previously performed in clinical samples addressing caregiver burden in pediatric chronic pain. Initiatives to reduce the burden of caring for children with chronic pain, described in prior work, may be especially beneficial for families with adolescents whose chronic pain is accompanied by other health problems or requires coordination of care among multiple providers.

Background and aims This paper forms part of a study evaluating the effect of patient-controlled oral analgesia for patients admitted to hospital with acute abdominal pain. Pain is a subjective experience, and a multifaceted evaluation tool concerning patient-reported outcome measures is needed to monitor, evaluate, and guide health care professionals in the quality of pain management. The Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) is a validated multifaceted evaluation tool for measuring patient-reported pain experiences to evaluate different pain management interventions. The aim of this study was to evaluate the psychometric properties of a modified Danish version of the Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R-D) used during and after hospitalization for patients with acute abdominal pain. Methods The APS-POQ-R was translated into Danish and two slightly different questionnaires were formed. Questionnaire one had 39 items and the six subscales pain severity (pain), perception of care (satisfaction), pain interference with function (activity) and emotions (emotion), side effects of treatment (safety), and patient-related barriers to pain management. The questionnaire focused on time during hospital stay and was to be completed at discharge. Questionnaire two included 25 items and the five subscales pain, satisfaction, activity, emotion, and safety and focused on time at home and was to be completed daily 1 week after discharge. The questionnaires were tested on 156 patients with acute abdominal pain. Internal consistency reliability and construct validity was examined. Results In both questionnaires, the results of correlations and tests for internal consistency reliability showed a Cronbach’s alpha of >0.7 for the pain, activity, and emotion subscales, but the value was ≥0.69 for the satisfaction subscale. In questionnaire one, Cronbach’s alpha was ≤0.64 for the safety subscale, but this was 0.73 when the item “itching” was deleted. In questionnaire two, Cronbach’s alpha was ≤0.51 for the safety subscale. For the patient-barrier subscale in questionnaire one, Cronbach’s alpha was ≤0.62 for any combination of the items in the subscale. The results of the construct validity and factor analysis showed a five-factor structure in questionnaire one and a three-factor structure in questionnaire two. In questionnaire one, items from the pain, activity, emotion, and safety subscales, except for the items “least pain” and “itching,” loaded on factor one. In questionnaire two, all items from the pain, activity, and emotion subscales loaded on factor one. Conclusions The modified APS-POQ-R-D demonstrated adequate psychometric properties for the five subscales pain severity (pain), perception of care (satisfaction), pain interference with function (activity) and emotions (emotion), side effects of treatment (safety), but not for the patient-barrier subscale for patients hospitalized with acute abdominal pain. Consequently, the APS-POQ-R-D may be used without the patient-barrier subscale. Implications The clinical implications of this study may help clinicians with investigating how acute patients manage pain during and after hospital admission.

Background and aims Musculoskeletal pain may negatively affect work ability, especially when work demands are high and/or physical capacity of the worker is low. This study investigated the association between intensity of musculoskeletal pain in multiple body regions and work ability among young and old workers with sedentary and physical demanding jobs. Methods Currently employed wage earners ( n =10,427) replied to questions about pain intensity, work ability, and physical work demands. The odds ratio (OR) for having a lower level of work ability in relation to the physical demands at work were modeled using logistic regression controlled for various confounders. Results The OR for lower work ability increased with higher pain intensity in all regions among workers with sedentary and physical work. The same pattern was observed among workers <50 years and ≥50 years in both work types. The association was quite consistent across age and work activity groups, although it tended to be more pronounced among those with physically demanding work in some of pain regions. Conclusions This study shows that increasing pain intensity in multiple sites of the body is associated with lower work ability. This was seen for both younger and older workers as well as those with sedentary and physical work. Implications Physical workers with multiple-site pain may especially be at increased risk of the consequences of reduced work ability. Therefore, extra attention is needed and this group may benefit from better targeted preventive measures.

Background and aims Achilles tendinopathy is common among runners, but the etiology remains unclear. High mechanical pain sensitivity may be a predictor of increased risk of developing Achilles tendinopathy in this group. The purpose of this study was to investigate whether local pain sensitivity could predict the development of Achilles tendinopathy in recreational male runners. The overall hypothesis was that high pain sensitivity would be related to a higher risk of developing Achilles tendinopathy among recreational male runners. Methods Ninety-nine recreational male runners were recruited and followed prospectively for 1 year. At baseline and after 500 km of running the pressure pain threshold (PPT) was assessed at the infraspinatus and at the Achilles tendon (AT-PPT). Based on the AT-PPT at baseline, a median split was used to divide the runners into two groups. The high pain sensitivity groups was defined as runners displaying a pain pressure threshold below 441 kPa on the Achilles tendon, while the low pain sensitivity group was defined as runners displaying a pain pressure threshold above 441 kPa on the Achilles tendon, respectively. Subsequently, the cumulative risk difference between the two groups was assessed by using the pseudo-observation method. Results High pain sensitivity runners sustained 5%-point (95% CI: −0.18 to 0.08) more Achilles tendinopathy episodes during the first 1,500 km. No significant group differences in risk were found at 100, 250, 500, 1,000 and 1,500 km of running. Conclusions No significant association was found between mechanical pain sensitivity in the Achilles tendon and the risk of developing Achilles tendinopathy. However, the risk difference indicated a association between a high mechanical pain sensitivity and an increased risk of developing Achilles tendinopathy. It is plausible that changes in pain sensitivity were masked by unmeasured covariates, such as the differences in progression/regression of training volume and running speed between the two groups. This study was limited in size, which limited the possibility to account for covariates, such as differences in progression/regression of running speed between runners. With the limitations in mind, future studies should control the training volume, speed and running shoes in the design or account for it in the analysis. Implications Pain sensitivity of the Achilles tendon seems not to be related to an increased risk of developing Achilles pain in relation to running.

Background and aims Body image as an increasing research field has been integrated into pain research within the last years. However, research on cognitive-affective dimensions of body image dependent on different pain groups like acute/subacute and chronic pain patients, and healthy controls is still lacking. Therefore, this study aims to explore three dimensions of body image, namely self-acceptance, physical efficacy, and health in patients with low back pain and healthy controls. The present study is the first to distinguish between patients with low back pain in different stages of pain with regard to the concept of body image. In a second step we investigated the differences in exercise frequency between the three groups. Methods Seventy seven patients (53.2% female) suffering from low back pain and 57 healthy controls (42.1% female) filled in a battery of questionnaires in terms of body image, pain parameters and exercise frequency. Results Main results indicate first that patients suffering from chronic low back pain revealed a more negative body image in all three body image-dimensions than healthy controls. Second, patients suffering from subacute pain revealed a more negative body image of physical efficacy compared to the healthy controls. Conclusions Our results suggest that body image is relevant for the treatment of low back pain, because patients suffering from low back pain revealed a more negative body image than healthy controls. Implications To investigate the cognitive-affective dimensions of body image in different patient groups suffering from low back pain seems to be an important aspect for future research to improve therapy options and prevention of low back pain. Future research should also focus on improvements or on positive aspects of body image in patients with low back pain.

Background and aims The objective was to conduct the first investigation to identify the frequency and intensity of pain experiences for individuals with CHARGE syndrome and to review the use of two established non-vocal pain assessments with children with CHARGE, the NCCPC-R (Non-Communicating Children’s Pain Checklist-Revised) and the PPP (Pediatrics Pain Profile). Methods Parents of children with CHARGE were enrolled. Participants completed a pain questionnaire and the NCCPC-R and PPP twice, once for a baseline measure and second during a painful experience for their child. Results A moderate negative correlation between the mean intensity of pain and the mean duration of pain among individuals with CHARGE was found, ρ=−0.34. There was a tendency for intensity of pain to increase for sources of pain that were of shorter duration. The NCCPC-R and PPP were found to identify pain when compared to baseline performance (no pain) with a large effect, d =1.3. For the NCCPC-R, the difference between these ratings was significant beyond the 0.05 level, t (40)=8.15, p =0.000, 95% CI [16.93, 28.10]. Similarly, for the PPP, the mean pain ratings were significantly greater than the mean ratings for no pain, with significance beyond the 0.05 level, t (51)=9.59, p =0.000, CI 95% [11.74, 17.96]. Conclusions Evidence exists that children with CHARGE experience pain. While the NCCPC-R and PPP were found to identify pain; future research should consider the development of a pain assessment individualized to pain behaviors present in CHARGE syndrome, given this population’s unique expression of pain.

Background and aims Fibromyalgia is a complex condition characterised by widespread pain, sleep disturbance, fatigue and cognitive impairment, with a global mean prevalence estimated at 2.7%. There are inconsistencies in guidelines on the treatment of fibromyalgia leading to dissatisfaction from patients and healthcare professionals. This study investigated patient-reported outcomes of pharmacological and non-pharmacological treatment usage and effectiveness with an assessment of acceptability. Methods Nine hundred and forty-one participants completed a self-administered anonymous questionnaire giving quantitative data of demographics, treatment usage and treatment outcomes. Participant-reported effectiveness and side effects were compared in the following treatment classes: analgesics, antidepressants, gabapentinoids, gastrointestinal treatments, activity interventions, dietary-based treatments, and psychological, physical and alternative therapies. Participants also reported whether they knew about or had tried different treatments. Results The results from the online survey indicated that the range of mean effectiveness ratings were similar for pharmacological and non-pharmacological treatments, whereas non-pharmacological treatments had lower side effects ratings and higher acceptability relative to pharmacological treatments. Participants were not aware of some treatment options. Conclusions The results show lower side effects ratings and higher acceptability for non-pharmacological treatments compared to pharmacological treatments despite similar effectiveness ratings. Implications This article presents results from a large online survey on fibromyalgia patient perspectives of pharmacological and non-pharmacological treatments. Results will inform healthcare professionals and patients about optimal treatments based on ratings of effectiveness, side effects and acceptability that are tailored to patient symptom profiles. Some participants were unaware of treatment options highlighting the importance of patient education allowing collaboration between patients and healthcare professionals to find optimal treatments.

Background and aims The interaction between the immune system and pain has been thoroughly explored in the recent decades. The release of inflammatory mediators from immune cells has the capability of activating neurons and glial cells, in turn sensitizing the nervous system. Both immune system alterations and pain modulation dysfunctions have been shown in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) following exercise. However, no studies tried to explore whether these two phenomena are linked and can explain exercise-induced symptoms worsening in people with ME/CFS. We hypothesized that exercise-induced changes in descending pain modulation is associated to changes in immune system functions. We used complement system product C4a and elastase activity as indicators of immune system activity. Methods The study design was a secondary analysis of controlled experimental studies. Twenty-two patients with ME/CFS and 22 healthy sedentary controls were enrolled. In experiment 1, subjects performed an aerobic submaximal exercise test; in experiment 2 they underwent a self-paced exercise test. One week of rest period were set between the two exercise tests. Before and after each experiment, subjects underwent clinical assessment, pain thresholds (PPTs) measurement, and blood sampling. Immune system function was assessed measuring complement system C4a products and elastase activity. Results Changes in elastase activity were not associated to changes in PPTs. Associations were observed in the ME/CFS group between changes in PPTs and C4a products, following both types of exercise. After submaximal exercise, the change in C4a products was associated with the change in PPT at the thumb in patients (r=0.669, p =0.001). Similarly, after self-paced exercise the change in C4a products was associated witht the change in PPT at the calf in patients (r=0.429, p =0.047). No such correlations were found in healthy controls. Regression analysis showed that C4a changes after the submaximal exercise significantly predicted the change in PPTs (R2=0.236; p =0.02). Conclusions Moderate associations between exercise-induced changes in PPTs and immune system activity were found only in ME/CFS. The change in the complement system following submaximal exercise might be able to explain part of the change in patient’s pain thresholds, providing evidence for a potential link between immune system alteration and dysfunctional endogenous pain modulation. These results have to be taken with caution, as only one out of three measures of PPTs was found associated with C4a changes. We cannot reject the hypothesis that C4a might therefore be a confounding factor, and changes during exercise might be mediated by other mechanism. Implications Immune system changes following exercise might contribute to exercise-induced symptoms worsening in patients with ME/CFS. However, the role of the complement system is questionable.

Background and aims We systematically characterized the potency and side effect profile of a series of small opioid peptides with high affinity for the mu opioid receptor. Methods Male Sprague Dawley rats were prepared with intrathecal (IT) catheters, assessed with hind paw thermal escape and evaluated for side effects including Straub tail, truncal rigidity, and pinnae and corneal reflexes. In these studies, DMT-DALDA (dDAL) (H-Dmt-D-Arg-Phe-Lys-NH 2 MW=981), dDALc (H-Dmt-Cit-Phe-Lys-NH 2 MW=868), dDALcn (H-Dmt-D-Cit-Phe-Nle-NH 2 MW=739), TAPP (H-Tyr-D-Ala-Phe-Phe-NH 2 MW=659), dDAL-TICP ([Dmt1]DALDA-(CH 2 ) 2 -NH-TICP[psi]; MW=1519), and dDAL-TIPP (H-Dmt-D-Arg-Phe-Lys(N ε -TIPP)-NH 2 were examined. In separate studies, the effects of approximately equiactive doses of IT DMT DALDA (10 pmol), morphine (30 nmol) and fentanyl (1 nmol) were examined on formalin-induced flinching at different pretreatment intervals (15 min – 24 h). Results (1) All agents resulted in a dose-dependent reversible effect upon motor function (Straub Tail>Truncal rigidity). (2) The ordering of analgesic activity (%MPE) at the highest dose lacking reliable motor signs after bolus delivery was: DMT-DALDA (80%±6/3 pmol); dDALc (75%±8/1 pmol); dDALcn (84%±10/300 pmol); TAPP (56%±12/10 nmol); dDAL-TICP (52%±27/300 pmol). (3) All analgesic effects were reversed by systemic (IP) naloxone (1 mg/kg). Naltrindole (3 mg/kg, IP) had no significant effect upon the maximum usable peptide dose. (4) Tolerance and cross-tolerance development after 5 daily boluses of DMT-DALDA (3 pmol) and morphine (30 nmol) revealed that both agents displayed a progressive decline over 5 days. (5) Cross-tolerance assessed at day 5 revealed a reduction in response to morphine in DMT-DALDA treated animal but not DMT-DALDA in the morphine treated animal, indicating an asymmetric cross-tolerance. (6) IT DMT-DALDA, morphine and fentanyl resulted in significant reductions in phase 1 and phase 2 flinching. With a 15 min pretreatment all drugs resulted in comparable reductions in flinching. However, at 6 h, the reduction in flinching after DMT-DALDA and morphine were comparably reduced while fentanyl was not different from vehicle. All effects on flinching were lost by 24 h. Conclusions These results emphasize the potent mu agonist properties of the DALDA peptidic structure series, their persistence similar to morphine and their propensity to produce tolerance. The asymmetric cross-tolerance between equiactive doses may reflect the relative intrinsic activity of morphine and DMT-DALDA. Implications These results suggest that the DALDA peptides with their potency and duration of action after intrathecal delivery suggest their potential utility for their further development as a spinal therapeutic to manage pain.

Background and aims The present study was designed to evaluate the relative efficacy of two video game display modalities – virtual reality (VR) assisted video game distraction, in which the game is presented via a VR head-mounted display (HMD) helmet, versus standard video game distraction, in which the game is projected on a television – and to determine whether environmental context (quiet versus noisy) moderates the relative efficacy of the two display modalities in reducing cold pressor pain in healthy college students. Methods Undergraduate students ( n =164) were stratified by sex and self-reported video game skill and were randomly assigned to a quiet or a noisy environment. Participants then underwent three cold pressor trials consisting of one baseline followed by two distraction trials differing in display modality (i.e. VR-assisted or standard distraction) in counter-balanced order. Results Participants experienced improvement in pain tolerance from baseline to distraction in both display modality conditions ( p <0.001, partial η 2 =0.41), and there was a trend toward greater improvement in pain tolerance from baseline to distraction when using the VR HMD helmet than during standard video game distraction ( p =0.057, partial η 2 =0.02). Participants rated pain as more intense when experienced with concurrent experimental background noise ( p =0.047, partial η 2 =0.02). Pain tolerance was not influenced by the presence or absence of background noise, and there was not a significant interaction between display modality and noise condition. Though exploratory sex analyses demonstrated a significant three-way interaction between noise condition, sex, and display modality on pain intensity ( p =0.040, partial η 2 =0.040), follow-up post-hoc analyses conducted for males and females separately did not reveal significant differences in pain intensity based on the interaction between noise condition and display modality. Conclusions As expected, video game distraction both with and without an HMD helmet increased pain tolerance; however, the two display modalities only marginally differed in efficacy within the population under study. The effect of auditory background noise on pain was mixed; while pain tolerance did not vary as a function of the presence or absence of background noise, the addition of noise increased pain intensity ratings. The interaction between participant sex, noise condition, and distraction modality on pain intensity trended toward significance but would require replication in future research. Implications Results suggest that video game distraction via HMD helmet may be superior to standard video game distraction for increasing pain tolerance, though further research is required to replicate the trending findings observed in this study. Though it does not appear that background noise significantly impacted the relative efficacy of the two different video game display modalities, the presence of noise does appear to alter the pain response through amplified pain intensity ratings. Further research utilizing more sophisticated VR technology and clinically relevant background auditory stimuli is necessary in order to better understand the impact of these findings in real-world settings and to test the clinical utility of VR technology for pain management relative to standard video game distraction.