Volume 22, Issue 1

Objectives Anger is a negative emotion characterized by antagonism toward someone or something, is rooted in an appraisal or attribution of wrongdoing, and is accompanied by an action tendency to undo the wrongdoing. Anger is prevalent in individuals with chronic pain, especially those with chronic primary pain. The associations between anger and pain-related outcomes (e.g., pain intensity, disability) have been examined in previous studies. However, to our knowledge, no systematic review or meta-analysis has summarized the findings of anger-pain associations through a focus on chronic primary pain. Hence, we sought to summarize the findings on the associations of anger-related variables with pain and disability in individuals with chronic primary pain. Methods All studies reporting at least one association between anger-related variables and the two pain-related outcomes in individuals with chronic primary pain were eligible. We searched electronic databases using keywords relevant to anger and chronic primary pain. Multiple reviewers independently screened for study eligibility, data extraction, and methodological quality assessment. Results Thirty-eight studies were included in this systematic review, of which 20 provided data for meta-analyses (2,682 participants with chronic primary pain). Of the included studies, 68.4% had a medium methodological quality. Evidence showed mixed results in the qualitative synthesis. Most anger-related variables had significant positive pooled correlations with small to moderate effect sizes for pain and disability. Conclusions Through a comprehensive search, we identified several key anger-related variables associated with pain-related outcomes. In particular, associations with perceived injustice were substantial.

Objectives Offset analgesia (OA) induces a brief pain inhibition and studies suggest OA impairment in patients with chronic pain when compared to healthy subjects. Conditioned pain modulation remains the most studied descending pain inhibitory control mechanism and is modulated by centrally-acting analgesics. Since OA may be mediated by similar neural substrates as conditioned pain modulation, understanding if OA is a peripheral or central proxy of pain modulation is important. The modulatory effect of centrally-acting drugs on OA in healthy and chronic pain populations has not yet been systematically reviewed and meta-analyzed, and this systematic review and meta-analysis aimed to identify studies employing interventions for modulating OA magnitude. Methods A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library yielded 146 records of which 11 (172 healthy pain-free subjects, 106 chronic pain patients) were eligible for qualitative synthesis, and 10 for meta-analysis on overall modulatory effect of interventions on OA, and subgroup analysis of patients and healthy pain-free subjects. Results Risk of bias was evident for study participation and study confounding in the included studies. Several different methods for assessing and calculating OA magnitude were identified, which may affect interpretability of findings and warrants standardization. The meta-analysis showed no modulatory effects on OA overall (standardized mean difference (SMD) [95%CI]: 0.04 [−0.22, 0.30], Z =0.29, p=0.77), or in the subgroup analysis for patients (SMD [95%CI]: −0.04 [−0.63, 0.71], Z =0.13, p=0.90) or healthy pain-free subjects (SMD [95%CI]: 0.01 [−0.21, 0.24], Z =0.11, p=0.91). Moderate to substantial heterogeneity was found for the overall analysis (I 2 =47%, p=0.03) and patient subgroup analysis (I 2 =75%, p=0.003). Conclusions The current systematic review and meta-analysis conclude that centrally-acting drugs and exercise do not influence OA. Evidence on the peripheral contribution to OA response requires further investigations. Preclinical models of OA should be established to identify the neurophysiology and -biology behind OA.

Objectives We aim to determine the effectiveness of meditation for adults with non-specific low back pain. Methods We searched PubMed, EMBASE, PEDro, Scopus, Web of Science, Cochrane Library, and PsycINFO databases for randomized controlled trials that investigated the effectiveness of meditation in adults with non-specific low back pain. Two reviewers rated risk of bias using the PEDro scale and the certainty of the evidence using the GRADE approach. Primary outcomes were pain intensity and disability. Results We included eight trials with a total of 1,234 participants. Moderate-certainty evidence shows that meditation is better than usual care for disability at short-term (SMD = −0.22; 95% CI = −0.42 to −0.02). We also found that meditation is better than usual care for pain intensity at long-term (SMD = −0.28; 95% CI = −0.54 to −0.02). There is no significant difference for pain intensity between meditation and minimal intervention or usual care at short and intermediate-term. We did not find differences between meditation and minimal intervention for disability at intermediate-term or usual care in any follow-up period. Conclusions We found small effect sizes and moderate-certainty evidence that meditation is slightly better than minimal intervention in the short-term for disability. Low-certainty of evidence suggests that meditation is slightly better than usual care for pain in the long-term. Meditation appears to be safe with most trials reporting no serious adverse events.

Objectives Application of spatially interlaced innocuous warm and cool stimuli to the skin elicits illusory pain, known as the thermal grill illusion (TGI). This study aimed to discriminate the underlying mechanisms of central and peripheral neuropathic pain focusing on pain quality, which is considered to indicate the underlying mechanism(s) of pain. We compared pain qualities in central and peripheral neuropathic pain with reference to pain qualities of TGI-induced pain. Methods Experiment 1:137 healthy participants placed their hand on eight custom-built copper bars for 60 s and their pain quality was assessed by the McGill Pain Questionnaire. Experiment 2: Pain quality was evaluated in patients suffering from central and peripheral neuropathic pain (42 patients with spinal cord injury, 31 patients with stroke, 83 patients with trigeminal neuralgia and 131 patients with postherpetic neuralgia). Results Experiment 1: Two components of TGI-induced pain were found using principal component analysis: component 1 included aching , throbbing , heavy and burning pain , component 2 included itching , electrical-shock , numbness , and cold-freezing . Experiment 2: Multiple correspondence analysis (MCA) and cross tabulation analysis revealed specific pain qualities including aching , hot-burning , heavy , cold-freezing , numbness , and electrical-shock pain were associated with central neuropathic pain rather than peripheral neuropathic pain. Conclusions We found similar qualities between TGI-induced pain in healthy participants and central neuropathic pain rather than peripheral neuropathic pain. The mechanism of TGI is more similar to the mechanism of central neuropathic pain than that of neuropathic pain.

Objectives The study aimed to investigate if patients with lumbar radicular pain only and those with combined lumbar radicular pain + radiculopathy differ in their somatosensory profiles and pain experiences. Methods Quantitative sensory testing (QST) was performed in 26 patients (mean age 47 ± 10 years, 10 females) with unilateral leg pain in the L5 or S1 distribution in their main pain area (MPA) and contralateral mirror side, in the relevant foot dermatome on the symptomatic side and in the hand dorsum. Pain experience was captured on the painDETECT. Results Eight patients presented with lumbar radicular pain only and 18 patients with combined radicular pain + radiculopathy. Patients with radicular pain only demonstrated widespread loss of function (mechanical detection) bilaterally in the MPA (p<0.003) and hand (p=0.002), increased heat sensitivity in both legs (p<0.019) and cold/heat sensitivity in the hand (p<0.024). QST measurements in the dermatome did not differ compared to HCs and patients with radiculopathy. Patients with lumbar radiculopathy were characterised by a localised loss of function in the symptomatic leg in the MPA (warm, mechanical, vibration detection, mechanical pain threshold, mechanical pain sensitivity p<0.031) and dermatome (mechanical, vibration detection p<0.001), consistent with a nerve root lesion. Pain descriptors did not differ between the two groups with the exception of numbness (p<0.001). Patients with radicular pain did not report symptoms of numbness, while 78% of patients with radiculopathy did. Conclusions Distinct differences in somatosensory profiles and pain experiences were demonstrated for each patient group, suggesting differing underlying pain mechanisms.

Objectives The Fibromyalgia Survey Diagnostic Criteria-2016 (FSD-2016 criteria) were recently recommended for both clinical and research purposes. The present study aims to examine whether there is concordance between clinician-based and FSD-2016 criteria-based diagnoses of FM, and secondly, to examine how the illness severity and physical function relate to the criteria-based diagnosis among patients referred to a rheumatism hospital. Methods Participants with a clinician-based diagnosis of FM were included consecutively when referred to a patient education programme for patients with FM. Illness severity was assessed with the Fibromyalgia Survey Questionnaire (FSQ). Based on the FSQ, the fulfilment of the FSD-2016 criteria was evaluated. Physical function was assessed using the Fibromyalgia Impact Questionnaire (FIQ) function scale and self-reported employment status. Results The sample included 130 patients (84% women) from 20 to 66 years of age. Eighty-nine per cent met the FSD-2016 criteria, and 44% of the patients were fully or partially employed. Great variability in illness severity was seen irrespective of employment status. There was an association between illness severity and physical function (r=0.4, p<0.001). For 95% of the patients, the FSQ illness severity scores classify as severe or very severe, and even for those not fulfilling the diagnostic criteria the scores were moderate and severe. Conclusions There was relatively high agreement between clinician- and criteria-based diagnoses. The illness severity overlapped irrespective of different employment status and fulfilment of FSD-2016 criteria.

Objectives With the International Classification of Diseases 11th revision (classifying fibromyalgia as a primary pain disorder) soon to be implemented, the importance of pain physicians being able to identify patients with fibromyalgia is emphasized. The diagnostic criteria proposed in 2016 are based on self-reported pain distribution and symptom severity. The study aimed to evaluate the diagnostic accuracy of the 2016 diagnostic criteria for fibromyalgia applied in a population of patients with high impact chronic pain referred for pain rehabilitation. Methods The study was performed as a diagnostic accuracy study at two Danish interdisciplinary pain rehabilitation centers, including 215 participants. All participants were evaluated clinically to identify patients with fibromyalgia. The diagnosis was based on expert opinion, but the minimum requirements were: (1) pain in all four body quadrants and axially for at least three months and (2) minimum 8 of 18 positive tender points. Participants filled in the fibromyalgia survey questionnaire, the patient version of the 2016 diagnostic criteria. Sensitivity, specificity, likelihood ratios, and positive and negative post-test probabilities were calculated using a clinical diagnosis of fibromyalgia as the reference standard. Results Based on clinical diagnosis 45% of the participants were diagnosed with fibromyalgia; of these, only 19% had been diagnosed previously. The 2016 diagnostic criteria demonstrated a sensitivity of 88.5%, a specificity of 81.5%, a positive likelihood ratio of 4.79, a negative likelihood ratio of 0.14, a positive post-test probability of 79.4%, and a negative post-test probability of 10.2%. Conclusions Fibromyalgia was severely under-diagnosed among patients with high impact chronic pain referred to tertiary care in two pain rehabilitation centers in Denmark. The 2016 diagnostic criteria showed sufficient discriminatory properties suggesting that the fibromyalgia survey questionnaire can be used as a screening tool assisting the identification of fibromyalgia in this patient population.

Objectives Perceived injustice is a theoretical construct comprising elements of loss, attribution of blame, and sense of unfairness. Patients with chronic pain often report high levels of perceived injustice, which can have negative impact on physiological and psychosocial aspects and treatment outcome. The Injustice Experience Questionnaire (IEQ) is a self-report 12-item questionnaire that shows good reliability and validity in patients with chronic pain. This study aimed to translate, validate, and expand the use of the Norwegian Injustice Experience Questionnaire (IEQ-N) to a chronic pain population. Methods A mixed-method approach was used to translate and validate the IEQ-N. It was forward-back translated, linguistically validated, and culturally adapted. Individual cognitive debriefing interviews (n=7) and a focus group interview (n=9) was used to explore the patients’ experience with- and understanding of the questionnaire. Statistical descriptive, correlational, factor- and regression analyses were used to investigate the IEQ-N validity, reliability, and factorial structure in a large registry sample (n=3,068) of patients with chronic pain. Results Patients with chronic pain found the IEQ-N relevant. Registry analyses supported that the IEQ-N had a one-factor structure. The internal consistency was high (Chronbach’s alpha=0.92). The construct validity was good, with moderate to strong significant univariate correlation (r=0.29–0.71) (p<0.05) between perceived injustice and related constructs of pain catastrophizing, pain severity, disability, psychological distress, and quality of life. Perceived injustice contributed with significant but small unique variance to pain-related factors (i.e., pain intensity, pain-related disability, psychological distress), but the additional contribution beyond pain catastrophizing was small (0.2–6.7%) (p<0.05). Conclusions Patients in the study found the questionnaire relevant for their situation, and easy to understand. This study provides a reliable and valid Norwegian tool to assess perceived injustice in patients with chronic pain. Ethical committee number REK sør-øst, 2016/1942.

Objectives Low-grade inflammation is a possible contributing factor in the development and persistence of chronic primary pain syndromes. Related to inflammatory activity is sickness behavior, a set of behavioral responses including increased pain sensitivity, fatigue, malaise, fever, loss of appetite, as well as depressive behavior and anhedonia. To capture these behavioral responses and their relation to longstanding pain, psychometrically sound self-report questionnaires are needed. The Sickness Questionnaire (SicknessQ) was developed to assess self-reported sickness behavior based on studies on acute immune activation while maintaining relevance for persistent conditions. The aim of the current study was to evaluate aspects of the validity and reliability of the SicknessQ in a Swedish sample of persons with longstanding pain. Methods Aspects of construct validity were evaluated by means of performing a confirmatory factor analysis (CFA) (testing structural validity) and by relevant hypothesis testing i.e., that ratings of sickness behavior in combination with other related factors (e.g., depression and anxiety) would be significantly related to ratings of avoidance. Reliability was evaluated by means of analyzing the internal consistency of items. Results Following the CFA, a non-significant Chi-Square test (χ 2 [32, N =190] = 42.95, p=0.094) indicated perfect model fit. Also, the relative fit indices supported adequate model fit (CFI = 0.978; TLI = 0.969; RMSEA = 0.0430). Sickness behavior (p<0.0001), depression (p<0.05) and pain duration (p<0.05) significantly contributed to the regression model, explaining 45% of the total variance in avoidance. Internal consistency was adequate, as indicated by a Cronbach’s α value of 0.82 for the entire questionnaire. Conclusions Results indicate that the SicknessQ has adequate structural validity as well as adequate internal consistency, and is significantly associated with avoidance. The SicknessQ appears to have utility as a self-report questionnaire to assess symptoms of sickness behavior for adults with longstanding pain.

Objectives Ketamine is used to treat chronic refractory pain. However, there are no scientific guidelines for ketamine use in the Netherlands. The aim of this survey was to provide an overview of the use of ketamine for chronic pain in the Netherlands. Methods All pain clinics in the Netherlands were contacted. A digital survey, available from June 2019 to January 2020, was sent to 68 pain clinics. The survey was completed by one pain physician as a representative of the entire pain department. The survey included questions about ketamine treatment indications, administration, dose, duration, treatment repetition and the inpatient or outpatient setting. Results The survey was completed by 51 pain clinics (75.0%). Thirty-one clinics used ketamine for chronic pain treatment. The most common indication was Complex Regional Pain Syndrome (83.9%). Pain clinics administered ketamine via intravenous infusions (96.8%), iontophoresis (61.3%), subcutaneous (3.2%) or oral administration (3.2%). Intravenous ketamine treatment was offered in an inpatient setting in 14 pain clinics, in both an inpatient and outpatient setting in 11 pain clinics and in six pain clinics in an outpatient setting. In the outpatient setting, the median starting dose was 5 mg/h (IQR=17.5–5). The median maximum dose was 27.5 mg/h (IQR=100–11.9). The median infusion duration was 6 h (IQR=8–4). In the inpatient setting, the median starting dose was 5 mg/h (IQR=5–1.5) and the median maximum dose was 25 mg/h (IQR=25–14). Patients were admitted to hospital for a median of 4 days (IQR=5–1). Conclusions The results of this Dutch nationwide survey study show that there are heterogeneous treatment protocols with different indications, treatment setting and dosing regimen for the treatment of chronic pain with ketamine. This study encourages the formulation of a broader consensus and the development of evidence based guidelines for ketamine treatment.

Objectives Sleep disturbances are increasingly recognized as a major part of chronic pain pathology. Obstructive sleep apnea (OSA) is a common occurrence in patients with chronic pain attending specialized pain clinics, yet its prevalence remains unclear. Using screening tools such as the Berlin and STOP-BANG questionnaires may aid in early identification of OSA and improve clinical care. This study i) examined the frequency of OSA based on objective sleep monitoring in patients with high-impact chronic pain, ii) explored potential differences in self-reported pain and sleep characteristics between patients with and without OSA, and iii) tested the agreement between OSA classification based on objective assessment and two OSA screening questionnaires. Methods A consecutive cohort of 90 patients (71 women and 19 men; mean age: 47.1 ± 11.0 years) referred for interdisciplinary pain treatment, underwent one night of sleep monitoring using portable respiratory polygraphy (RP), and suspected OSA was confirmed with polysomnography (PSG). Self-reported data on clinical pain (severity, pain drawings and health-related quality of life), sleep characteristics (sleep quality insomnia, sleepiness), and risk of OSA (Berlin and STOP-BANG questionnaires) were collected the day before RP assessment. Results Forty-six (51.1%) patients were classified with OSA according to RP and verified with PSG. Twenty-eight patients (31.1%) had moderate or severe OSA (apnea-hypopnea index [AHI] >15). Patients with OSA reported lower sleep quality compared with patients without OSA. Scores on pain severity, disability, quality of life, insomnia and sleepiness were comparable between patients with and without OSA. Sensitivity and specificity were 78.6 and 45.2% respectively for the Berlin questionnaire, and 71.4 and 58.1% respectively for the STOP-BANG questionnaire. The agreement for both questionnaires with objective assessment was poor-to-fair. Both questionnaires had acceptable negative predictive values but low positive predictive values reducing the clinical utility to identify patients with low OSA-risk in this sample. Conclusions The current study demonstrates a high prevalence of OSA in patients with high-impact chronic pain referred to specialized pain treatment, however the clinical pain profiles were similar in patients with and without OSA. The Berlin and STOP-BANG questionnaires have poor specificity and low-to-fair agreement with RP/PSG questioning their clinical utility in identifying OSA in this sample.

Objectives Previous findings suggest that abusive supervision, i.e., subordinates’ perceptions of their supervisor’s behaviours as hostile (excluding physical aggression), may increase the risk of health complaints. In addition, recent data suggest that the FKBP5 genotype rs9470080 important in the regulation of cortisol release, influences the same outcome. Adding to this complexity, different health complaints often co-occur. The present study aimed to (1) uncover patterns of pain complaints and insomnia symptoms by using latent class analysis, (2) determine whether abusive supervision or FKBP5 rs9470080 was associated with these patterns, and (3) examine the interaction between abusive supervision and FKBP5 genotype regarding pain and insomnia symptoms. Methods The data was collected through a national probability survey of 5,000 employees drawn from the National Central Employee Register by Statistics Norway. Abusive supervision was measured by a 5-item version of the Tepper’s 2000 scale. Pain and insomnia symptoms were measured by 5 items reflecting pain and 3 items reflecting insomnia. The FKBP5 rs9470080 genotyping was carried out using TaqMan assay. Results A total of 1,226 participants returned the questionnaire and the saliva kit sample. Based on these the latent class analyses revealed four classes based on response patterns of pain and insomnia symptoms. In the regression analysis, abusive supervision was a significant predictor for the response patterns. However, neither the FKBP5 nor the interaction between abusive supervision and FKBP5 showed significant contributions. Conclusions In conclusion, awareness of the association between abusive supervision and the revealed four pain- and insomnia subgroups, and what separates them, may be important for prognosis and an optimal follow-up for those affected.

Objectives The population of Americans with limb loss is on the rise, with a different profile than in previous generations (e.g., greater incidence of amputation due to diabetes). This study aimed to identify the key characteristics of phantom limb sensation (PLS) and pain (PLP) in a current sample of Americans with limb loss. Methods This cross-sectional study is the first large-scale (n=649) study on PLP in the current population of Americans with limb loss. A convenience sample of military and civilian persons missing one or more major limbs was surveyed regarding their health history and experience with phantom limb phenomena. Results Of the participants surveyed, 87% experienced PLS and 82% experienced PLP. PLS and PLP typically first occurred immediately after amputation (47% of cases), but for a small percentage (3–4%) onset did not occur until over a year after amputation. Recent PLP severity decreased over time (β=0.028, 95% CI: −0.05–0.11), but most participants reported PLP even 10 years after amputation. Higher levels of recent PLP were associated with telescoping (β=0.123, 95% CI: 0.04–0.21) and higher levels of pre-amputation pain (β=0.104, 95% CI: 0.03–0.18). Those with congenitally missing limbs experienced lower levels of recent PLP (t (37.93)=3.93, p<0.01) but there were no consistent differences in PLP between other amputation etiologies. Conclusions Phantom limb phenomena are common and enduring. Telescoping and pre-amputation pain are associated with higher PLP. Persons with congenitally missing limbs experience lower levels of PLP than those with amputation(s), yet PLP is common even in this subpopulation.

Objectives Healthcare expenditures of older United States (US) adults with different pain severity levels are important to investigate given the increasing prevalence of pain in this population. This study assessed the correlation of healthcare expenditures among older US adults with different pain severities, hypothesizing that expenditures would increase as pain severity increased. Methods This retrospective cross-sectional database study used 2018 Medical Expenditure Panel Survey (MEPS) data and included US adults aged ≥50 with self-reported pain in the past four weeks and positive healthcare costs. Adjusted linear regression models with logarithmically transformed expenditure data compared differences in: total; office-based; outpatient; emergency room; inpatient; other; and prescription medication expenditures, between those with little, moderate, quite a bit, and extreme pain. Analyses were weighted to account for the complex MEPS design and to obtain nationally representative estimates. The a priori alpha level was 0.05. Results The eligible sample of 5,123 individuals produced a weighted study population of 57,134,711 US adults aged ≥50 with pain (little = 53.1%, moderate = 21.6%, quite-a-bit = 18.5%, extreme = 6.8%). In adjusted linear regression models, compared to little pain, extreme pain had the greatest level of costs, followed by quite a bit pain and moderate pain, for total, office-based, and prescription medication costs. For instance, compared to little pain, total healthcare costs were 78% greater for those with extreme pain, 51% greater for quite a bit pain, and 37% greater for moderate pain. However, this pattern was not observed for outpatient, emergency room, inpatient, and other costs, where ≥1 comparison for each cost category was not statistically significant. Conclusions This study found total healthcare costs increased as pain severity increased, yet this was not always the case when analyzing subcategories of healthcare costs. Further research is needed to investigate why some types of healthcare costs are greater with increasing pain severity, yet others are not.

Objectives We investigated the associations between health-related quality of life (HRQoL) and health, pain and lifestyle factors, as well as motivation for lifestyle changes, in adults living with chronic pain referred to a Danish pain centre. Methods A total of 144 outpatients completed a questionnaire on HRQoL (EQ-5D-5L), health, pain, lifestyle factors (Body Mass Index [BMI], physical activity, smoking, alcohol, physical fitness, eating, sleep and stress) and motivation for lifestyle changes. We used multiple linear regression analyses to assess associations between HRQoL and the independent variables. Results The participants (age mean 50 years, 81% females) had ≥2 body pain sites (93%), BMI≥25 (64%), sedentary lifestyle (43%) and multiple (n≥2) elevated metabolic risk factors (58%). Most considered lifestyle important for HRQoL (72%) and expressed moderate to very high motivation for changing lifestyle (92%). Poorer HRQoL in the study population was significantly associated with higher pain intensity in the most painful body site (β=−0.316, p=0.001) and very poor sleep quality (β=−0.410, p=0.024). Serious-to-extreme problems in usual activities were associated with significantly poorer health (β=−0.328, p=0.030). Conclusions Adults living with chronic pain participating in this survey had significantly lower self-evaluated HRQoL than the general population. Lower HRQoL was significantly associated with greater pain intensity and poor sleep quality. Serious-to-extreme problems in usual activities, such as work, study, housework, family and leisure, were associated with poorer self-evaluated health. We observed high frequencies of overweight, obesity, sedentary lifestyle, pain in multiple body sites and multiple lifestyle-related risk factors in the study population. Most participants felt motivated for changing lifestyle. Further interventions addressing pain alleviation, sleep quality, prevention of problems in usual activities and promotion of healthy lifestyle, e.g. physical activity and healthy eating, are needed to estimate the effect of a lifestyle-oriented approach on health and quality of life in people living with chronic pain. The results of this study will inform the research project reg. SJ-703, the Danish the Research Ethics Committee for Region Zealand, Denmark.

Objectives Clinical decisions rely on a patient’s ability to recall and report their pain experience. Monitoring pain in real-time (momentary pain) may reduce recall errors and optimize the clinical decision-making process. Tracking momentary pain can provide insights into detailed changes in pain intensity and distribution (area and location) over time. The primary aims of this study were (i) to measure the temporal changes of pain intensity, area, and location in a dose-response fashion and (ii) to assess recall accuracy of the peak pain intensity and distribution seven days later, using a digital pain mapping application. The secondary aims were to (i) evaluate the influence of repeated momentary pain drawings on pain recall accuracy and (ii) explore the associations among momentary and recall pain with psychological variables (pain catastrophizing and perceived stress). Methods Healthy participants ( N =57) received a low (0.5 ml) or a high (1.0 ml) dose of hypertonic saline (5.8%) injection into the right gluteus medius muscle and, subsequently, were randomized into a non-drawing or a drawing group. The non-drawing groups reported momentary pain intensity every 30-s. Whereas the drawing groups reported momentary pain intensity and distribution on a digital body chart every 30-s. The pain intensity, area (pixels), and distribution metrics (compound area, location, radiating extent) were compared at peak pain and over time to explore dose-response differences and spatiotemporal patterns. All participants recalled the peak pain intensity and the peak (most extensive) distribution seven days later. The peak pain intensity and area recall error was calculated. Pain distribution similarity was determined using a Jaccard index which compares pain drawings representing peak distribution at baseline and recall. The relationships were explored among peak intensity and area at baseline and recall, catastrophizing, and perceived stress. Results The pain intensity, area, distribution metrics, and the duration of pain were lower for the 0.5 mL than the 1.0 mL dose over time (p<0.05). However, the pain intensity and area were similar between doses at peak pain (p>0.05). The pain area and distribution between momentary and recall pain drawings were similar (p>0.05), as reflected in the Jaccard index. Additionally, peak pain intensity did not correlate with the peak pain area. Further, peak pain intensity, but not area, was correlated with catastrophizing (p<0.01). Conclusions This study showed differences in spatiotemporal patterns of pain intensity and distribution in a dose-response fashion to experimental acute low back pain. Unlike pain intensity, pain distribution and area may be less susceptible in an experimental setting. Higher intensities of momentary pain do not appear to influence the ability to recall the pain intensity or distribution in healthy participants. Implications The recall of pain distribution in experimental settings does not appear to be influenced by the intensity despite differences in the pain experience. Pain distribution may add additional value to mechanism-based studies as the distribution reports do not vary with pain catastrophizing. REC # N-20150052

Objectives Scientific evidence suggests that virtual reality (VR) could potentially help patients tolerate painful medical procedures and conditions. The aim of this study was to evaluate the efficacy of virtual reality on pain tolerance and threshold. Methods A within-subjects experimental study design was conducted on 53 female students at Qassim University in Saudi Arabia. Each participant completed three rounds of assessment: one baseline (no VR) and two VR immersion (passive and interactive) in random order sequence. During each round, participants submerged their non-dominant hand into an ice bath; pain threshold and tolerance were measured as outcomes and analyzed using repeated measures ANOVA. Results Participants had both higher pain threshold and tolerance during interactive and passive VR rounds in comparison to the non-VR baseline assessment (p<0.05). Participants had greater pain tolerance during the interactive VR condition compared to the passive VR condition (p<0.001). Conclusions VR experiences increase pain threshold and tolerance with minimal side effects, and the larger effects were demonstrated using interactive games. Interactive VR gaming should be considered and tested as a treatment for pain.

Objectives Cognitive inhibition, which denotes the ability to suppress predominant or automatic responses, has been associated with lower pain sensitivity and larger conditioned pain modulation in humans. Studies exploring the association between cognitive inhibition and other pain inhibitory phenomena, like exercise-induced hypoalgesia (EIH), are scarce. The primary aim was to explore the association between cognitive inhibition and EIH at exercising (local) and non-exercising (remote) muscles after isometric exercise. The secondary aim was to explore the association between cognitive inhibition and pressure pain sensitivity. Methods Sixty-six pain-free participants (28.3 ± 8.9 years old, 34 women) completed two cognitive inhibition tasks (stop-signal task and Stroop Colour-Word task), a 3-min isometric wall squat exercise, and a quiet rest control condition with pre- and post-assessments of manual pressure pain thresholds at a local (thigh) and a remote site (shoulder). In addition, cuff pressure pain thresholds, pain tolerance and temporal summation of pain were assessed at baseline. Results No association was found between remote EIH and cognitive inhibition (Stroop interference score: r=0.12, [−0.15; 0.37], p=0.405, BF01=6.70; stop-signal reaction time: r=−0.08, [−0.32; 0.17], p=0.524, BF01=8.32). Unexpectedly, individuals with worse performance on the Stroop task, as indicated by a higher Stroop interference score, showed higher local EIH (r=0.33; [0.10; 0.53], p=0.007, BF01=0.29). No associations were observed between pain sensitivity and any of the cognitive inhibition performance parameters. Conclusions The present findings do not support previous evidence on positive associations between exercise-induced hypoalgesia and cognitive inhibition, as well as baseline pain sensitivity and cognitive inhibition.

Objectives To alleviate different pain intensities, morphine administration has been extensively used. However, prolonged administration of morphine leads to a progressive decline of its analgesic effect which limits their overall utility. Morphine tolerance is considered as a challenging issue for the treatment of both acute and chronic pain. We conducted this study in rats to investigate the effect of paroxetine on morphine tolerance when used preemptively or after morphine tolerance had developed. Methods Male Wistar rats (weight 250–300 g, n=10) were used to evaluate the effects of paroxetine on tolerance to morphine. In order to induce tolerance, daily intraperitoneal injection of morphine (7 mg/kg) was done. After tolerance induction, a group of animals received intraperitoneal injection of 10 mg/kg paroxetine 30 min prior to each morphine dose. In another trial, to investigate the potential of paroxetine to prevent tolerance to morphine, animals were pretreated with 10 mg/kg paroxetine 30 min before morphine administration. In the control groups, 10 mL/kg of saline was injected. The behavioral test (tail-flick test) was done for all groups. Results Our data showed that paroxetine significantly reversed tolerance to morphine when used after tolerance induction (p<0.001). However, administration of paroxetine before occurrence of tolerance had no effect. Conclusions We conclude that paroxetine could decrease tolerance to morphine when used after the occurrence of morphine tolerance, while it was not able to prevent morphine tolerance when administered preemptively. Ethical committee number IRIB.SBMU.MSP.REC.1394.098.

Objectives The most notable adverse side effects of chronic morphine administration include tolerance and hyperalgesia. This study investigated the involvement of dorsal root ganglion (DRG) protein kinase Cɛ (PKCɛ) expression during chronic morphine administration and also considered the relationship between DRG PKCɛ expression and the substance P- neurokinin1 receptor ( SP- NK1R) activity. Methods Thirty-six animals were divided into six groups (n=6) in this study. In the morphine and sham groups, rats received 10 µg intrathecal (i.t.) morphine or saline for eight consecutive days, respectively. Behavioral tests were performed on days 1 and 8 before and after the first injections and then 48 h after the last injection (day 10). In the treatment groups, rats received NK1R antagonist (L-732,138, 25 µg) daily, either alone or 10 min before a morphine injection, Sham groups received DMSO alone or 10 min before a morphine injection. Animals were sacrificed on days 8 and 10, and DRG PKCɛ and SP expression were analyzed by western blot and immunohistochemistry techniques, respectively. Results Behavioral tests indicated that tolerance developed following eight days of chronic morphine injection. Hyperalgesia was induced 48 h after the last morphine injection. Expression of SP and PKCɛ in DRG significantly increased in rats that developed morphine tolerance on day 8 and hyperalgesia on day 10, respectively. NK1R antagonist (L-732,138) not only blocked the development of hyperalgesia and the increase of PKCɛ expression but also alleviated morphine tolerance. Conclusions Our results provide evidence that DRG PKCɛ and SP-NK1R most likely participated in the generation of morphine tolerance and hyperalgesia. Pharmacological inhibition of SP-NK1R activity in the spinal cord suggests a role for NK1R and in restricting some side effects of chronic morphine. All experiments were performed by the National Institute of Health (NIH) Guidelines for the Care and Use of Laboratory Animals (NIH Publication No. 80-23, revised1996) and were approved by the Animal Ethics Committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran (IR.SBMU.MSP.REC.1396.130).

Objectives Hemicrania continua (HC) is one of the trigeminal autonomic cephalalgias (TAC), where sympathetic dysfunction and autonomic dysfunction resulting in parasympathetic over activation with some evidence of sympathetic inhibition have been suggested as probable causes. However, cases of hemicrania continua secondary to sympathetic dysfunction due to neurogenic paravertebral tumor impinging on the sympathetic chain has not been previously reported. In this case, the probability of the sympathetic dysfunction was more likely based on the clinical features and management. Case presentation A 23-year-old female presented with a chief complaint of right unilateral pain in the retro-bulbar, head and facial region for the past three years. An initial MRI of the brain was negative, whereas an MRI of the spine was advised to rule out a cervicogenic origin of the pain. The MRI revealed a well-defined mass lesion within right paravertebral region at T3 indicative of a neurogenic tumor. The patient was diagnosed with probable hemicrania continua secondary to neurogenic tumor impinging on adjacent sympathetic chain. A trial of indomethacin 75 mg/day was advised, which provided complete relief of the headache. The patient was referred to a neurologist for management of the neurogenic tumor. Conclusions Headache disorders may be secondary to pathologies and comprehensive evaluation and accurate diagnosis are essential. Knowledge of neuroanatomy is paramount to understand and explain underlying pathophysiological mechanisms. Multidisciplinary management is essential in complex orofacial cases.