Volume 23, Issue 2

Objectives Patients suffering from chronic pain experience significant disability and disease burden. Resilience has been understood to be a protective factor in face of adversity, eventually contributing to positive outcomes. As such, the current review sought to summarize the existing literature focusing on the roles of resilience in relation to pain phenomenology, pain outcomes (including function and mental health), amongst relevant clinical correlates in a bid to promote holistic management of debilitating chronic pain conditions from a resilience-oriented psychotherapeutic approach as an adjunct to pharmacological treatment. Methods A scoping review was conducted on empirical studies surrounding the theme of resilience in adult chronic pain populations published before 9th May 2021. The following main inclusion criteria was applied; (a) adults diagnosed with chronic pain disorders, (b) use of quantifiable pain measures, (c) use of quantifiable resilience measures. A total of 32 studies were then selected for the review. Results First, higher levels of resilience were associated with a reduced likelihood of experiencing any chronic pain, fewer pain sites, better psychological response towards nociception and reduced need for analgesia. Second, higher levels of resilience correlated with better daily and physical function, quality of life, psychosocial functioning and lower likelihood of co-morbid mental health disorders. Third, resilience was an intermediary variable in the pathways from pain phenomenology leading to pain interference, depression and post-traumatic growth. Conclusions The findings were contextualized using pain-disability and resilience frameworks (The Pain and Disability Drivers Model, O’Leary’s Resilience models) with suggestions to enhance resilience and contextual factors in the holistic management of adult chronic pain conditions. Future research should examine the differences in resilience between pain types as well as evaluate the efficacy of streamlined resilience-oriented interventions.

A growing worldwide focus on opioid-free anaesthesia entails multimodal analgesic strategies involving non-opioids such as magnesium sulphate (MgSO 4 ). Several systematic reviews have concluded there is beneficial analgesic effect of MgSO 4 administration but do not take considerable heterogeneity among the studies into consideration. Medical literature published until June 2021 was searched in PubMed/Medline, Embase, Central and Web of Science: The final search yielded a total of 5,672 articles. We included only randomised controlled trials assessing the effect of intravenous MgSO 4 on opioid consumption and acute postoperative pain when compared to either placebo or standardized analgesic treatment. The primary aim was to compare the homogeneity of essential variables and confounders. A post-hoc meta-analysis demonstrated a reduction in both postoperative morphine consumption (−6.12 mg) and pain score (−12.32 VAS points) in favour of the MgSO 4 -groups. Data for meta-analysis was missing from 19 studies (45%) on morphine consumption and 29 studies (69%) for pain score, the majority of which reports no effect for either morphine consumption or pain score. The calculated heterogeneity among the included studies was considerable for both outcomes; I 2 =91% for morphine consumption and I 2 =96% for pain score. Although we found a per se reduction in opioid consumption and pain score, methodological heterogeneity and clinical shortcomings of pre-, intra-, and post anaesthetic data precludes conclusions on clinical importance of intraoperative intravenous MgSO 4 . In addition, the reduction is likely less than what can be gained from using standardized analgesic treatment.

Objectives To give an overview of central aspects of pain medicine-specific clinical reasoning when assessing a pain patient. Clinical reasoning is the thinking and decision-making processes associated with clinical practice. Methods Three core pain assessment areas that are crucial for clinical reasoning in the field of pain medicine are discussed, each of them consisting of three points. Results First, it is important to distinguish acute, chronic non-cancer, and cancer-related pain conditions. This classical and very simple trichotomy still has important implications treatment-wise, e.g., concerning the use of opioids. Second, the pain mechanism needs to be assessed. Is the pain nociceptive, neuropathic, or nociplastic? Simply put, nociceptive pain has to do with injury of non-neural tissue, neuropathic pain is caused by a disease or lesion of the somatosensory nervous system, and nociplastic pain is believed to be related to a sensitized nervous system (c.f. the concept of “central sensitization”). This also has implications concerning treatment. Some chronic pain conditions are nowadays viewed more as diseases rather than the pain being merely a symptom. In the new ICD-11 pain classification, this is conceptualized by the characterization of some chronic pains as “primary”. Third, in addition to a conventional biomedical evaluation, psychosocial and behavioral aspects must also be assessed, the pain patient being viewed as an active agent and not merely as the passive recipient of an intervention. Hence, the importance of a dynamic bio-psycho-social perspective. The dynamic interplay of biological, psychological, and social aspects must be taken into account, putative behavioral “vicious circles” thereby being identified. Some core psycho-social concepts in pain medicine are mentioned. Conclusions The clinical applicability and clinical reasoning power of the 3 × 3 framework is illustrated by three short (albeit fictional) case descriptions.

Objectives Despite the number of people affected by chronic back pain, and the many available treatment options, even the best modalities provide limited pain reduction on a group level, often without simultaneous improvements in functioning or health-related quality of life. The objective was to provide an overview of the treatment of chronic back pain in clinical practice at a multidisciplinary pain centre, and to study patient and pain characteristics in different treatment groups. Methods 104 chronic back pain patients (primary ICD-10-SE-diagnosis M53.0–M54.9 excluding M54.1 and M54.3), referred to the Pain and Rehabilitation Centre, University Hospital, Linköping in 2015, were studied using data from the Swedish Quality Registry for Pain Rehabilitation, self-reported medication data, and a retrospective medical record review. Results The following treatment groups were identified: rehabilitation (n=21), analgesics (n=33), invasive intervention (n=14), and no treatment (n=35). Significant differences between groups were found with regards to age, sick leave, education level, persisting pain duration, punishing responses by significant other, previous invasive intervention, receiving sub-clinic, physician speciality and referring care level. Conclusions Overall, patient demographics were associated with treatment strategy to a higher degree than patient-reported outcome measures. Moreover, physician speciality and organisational factors seemed to play a role in treatment choice.

Objectives Comorbid with chronic pain are negative emotions, anger being particularly salient. To evaluate specific relationships between pain and anger, the present study deconstructed anger into five parameters and dichotomized pain into sensory vs. affective components. Hypotheses were (i) anger parameters would be significantly and positively correlated with affective pain more so than with sensory pain, and (ii) individual parameters would be differentially related to pain components. Methods The Anger Parameters Scale (APS) was used to rate five parameters of anger: frequency, duration, intensity, latency, and threshold. Also rated was the physical sensation of pain and the degree of distress from pain. The volunteer sample comprised n=51 chronic pain patients, varying in ethnicity/race and educational level. Results Descriptive statistics revealed: APS total M=71.52, SD=16.68, Sensory pain M=6.27, SD=2.15, Affective pain M=5.76, SD=2.28. Sensory and affective pain were highly correlated, r=0.70. APS total was significantly associated with affective pain (r=+0.28) but hardly with sensory pain (r=0.12). Two anger parameters significantly correlated with affective pain: anger frequency (r=+0.30, p<0.05) and anger threshold (r=+0.33, p<0.05). Secondarily, certain educational levels (but not gender and ethnicity/race) were associated with significantly higher APS total scores. Conclusions Scores for all variables were in the mid-range. As hypothesized, anger was more strongly correlated with distress/suffering of pain than with physical sensation of pain, though both pain components were closely coupled. Specific findings regarding frequency and threshold imply that being angry often and being oversensitive to provocation are associated with greater distress in this context. In deconstructing anger and dichotomizing pain, the present study extends previous research by elaborating on what aspects of anger are most related to which components of pain. Moreover, certain educational levels with higher levels of anger may need special attention. Further research could examine if treatment of anger might lead to corresponding changes in chronic pain.

Objectives Patients with somatoform disorders often experience loneliness. They feel misunderstood and socially rejected. Whereas loneliness is related to several medical conditions, social support can minimize loneliness. In the current study, differences in loneliness and the evaluation of social support between patients with Somatic Symptom Disorder (SSD) and healthy controls were investigated using standardized questionnaires. In addition, the relation between loneliness and somatic symptoms was investigated. Methods In a cross-sectional study design, a group of patients with SSD (n=75) was compared to a healthy control group (n=112). It was hypothesized that [1] patients with SSD experience more loneliness and evaluate their social support more negatively than healthy controls and [2] loneliness will correlate positively with experienced somatic symptoms. Results In comparison to healthy controls, patients with SSD experienced more loneliness and their evaluation of social support was more negative. In addition, loneliness correlated positively with the degree of experienced somatic symptoms. Conclusions Patients with SSD experienced lower social support, more loneliness, and across the two groups loneliness was positively associated with somatic symptoms. Effect sizes were all large. Therefore, these results may have implications for the treatment of SSD.

Objectives The Fear-Avoidance Components Scale (FACS) is a recently developed patient-reported instrument assessing different constructs related to the fear-avoidance model of pain. The aim was to translate the original English FACS into Dutch (FACS-D) and assess its measurement properties in persons with chronic musculoskeletal pain. Methods The original English FACS (20 item-scale, range: 0–100) was translated in Dutch through standard forward-backward translation methodology. The FACS-D’s measurement properties were evaluated in 224 persons with chronic musculoskeletal pain. Internal consistency, test-retest reliability and measurement error were assessed with the Cronbach’s alpha coefficient (α), intraclass correlation coefficient (ICC), and standard error of measurement (SEM). Construct validity was assessed through inter-item correlation analyses, exploratory factor analysis, association with other fear-avoidance-related constructs, and hypothesis testing. Results Internal consistency, test-retest reliability and hypotheses testing were good (α=0.92; ICC=0.92, CI 0.80–0.96; 7/8 hypotheses confirmed). Similar to the original FACS and other translated versions, a two-factor model best fit the data. However, the item distribution differed from other versions. One factor represented “pain-related cognitions and emotions” and a second factor represented “avoidance behaviour.” In contrast to the original FACS, low inter-item correlations for item 12 were found. The FACS-D was more strongly associated with fear-avoidance-related constructs of pain severity, perceived disability, feelings of injustice, and depressive/anxiety symptoms than the other fear-avoidance-related scales studied here. Conclusions The FACS-D demonstrated good reliability and construct validity, suggesting that it may be a useful measure for Dutch-speaking healthcare providers. Two clinically relevant factors, with a different item distribution than the original FACS, were identified: one covering items on pain-related cognitions and emotions, and one covering items on avoidance behaviour. The stronger association between FACS-D and fear-avoidance related constructs suggests that the FACS-D may be more effective in evaluating the cognitive, emotional and behavioural constructs of pain-related fear-avoidance than other similar measures.

Objectives Although neurobiological research has shown that interoception plays a role in the perception of pain and its chronification, the relationship between interoceptive sensitivity and pain has not been definitively confirmed by clinical studies. The aim of this study was therefore to better understand the relationship between interoceptive sensitivity, somatization, and clinical pain, and to identify any differences in the interoceptive sensitivity of patients with recurrent vs. chronic pain. Methods Scores from 43 Chronic pain subjects, assessed using ICD-11 Criteria; 42 healthy subjects (without pain or psychiatric disorders); and 38 recurrent pain subjects on the Multidimensional Assessment of Interoceptive Awareness (MAIA), Body Perception Questionnaire (BPQ-SF), Somatosensory amplification scale (SSAS), Patient Health Questionnaire (PHQ-15), Symptom Checklist-Revised (SCL-90-R), and Italian Pain Questionnaire (IPQ) were compared. Results Negative attention to the body was indicated by higher scores of psychosomatic dimensions as SSAS, SCL90R somatization, and PHQ-15 in recurrent, but especially chronic pain (p<0.000 for all). An increase in psychosomatic dimension scores (i.e., somatization, somatosensory amplification) was associated with an increase in both autonomic nervous system reactivity (ANSR) dimension scores and the negative influence of the Not-worrying, attention regulation and trusting of the MAIA. In contrast, the presence of pain and scores for its dimensions with associated with lower supra-diaphragmatic activity as per the BPQ. Conclusions Pain chronification might depend on both the impairment of interoceptive sensitivity and an increase on psychosomatic dimensions via modification of ANSR hyperactivity and a reduction of the MAIA Not-worrying dimension.

Objectives Several studies have demonstrated posttraumatic stress disorder (PTSD) and chronic pain comorbidity. However, there is a lack of research on the psychological variables that might explain their co-occurrence. We investigated the mediating role of distress intolerance and pain catastrophizing in this relationship. Methods A moderated mediation model was tested. The sample comprised 114 individuals with chronic noncancer pain (90 women and 24 men; mean age, of 60.04 years [SD=9.76]). Results Catastrophizing had a significant effect on PTSD. Distress intolerance mediated catastrophizing and PTSD, and pain intensity moderated this relationship. Conclusions New insights are provided into the psychological variables that may explain PTSD and chronic noncancer pain comorbidity.

Objectives Earlier findings suggest that social stress such as abusive supervision may promote pain. In the present study we examine the possible moderating role of genetic variability in the NRCAM gene in this process. Methods The data were collected through a national survey drawn from the National Central Employee Register by Statistics Norway. A total of 1,205 individuals returned both the questionnaire and the saliva kit. Abusive supervision was scored by a 5-item version of the Tepper’s 2,000 scale. Headache was measured on a four-category scale; ‘not bothered,’ ‘a little bothered,’ ‘considerably bothered’, ‘seriously bothered’. Genotyping with regards to NRCAM rs2300043 was carried out using Taqman assay. Ordinal logistic regression was used to analyse the data. Results For males exposed to abusive supervision, those carrying the rs2300043 CC genotype reported the highest levels of headache. Women showed a trend towards the opposite pattern. Women with the rs2300043 CC genotype seem to have a weaker effect of abusive supervision regarding reported headache than their male counterparts with the CC genotype when exposed to abusive supervision. Conclusions The present results indicated that the association between abusive supervision and headache in men with the NRCAM rs2300043 C allele was stronger than in other men. This suggests that the NRCAM genotype in men is important for the tolerance of social stress e.g., repeated negative acts from a superior. In contrast, a trend, though non-significant, towards the opposite pattern was observed in women. Our result suggests that the NRCAM genotype in men manifestly affects stress-induced pain such as headache.

Objectives This study explored the relationship between sleep quality and next-day pain intensity for people with low back pain and investigated whether there was any evidence that this relationship was causal. Methods We conducted a secondary analysis of an observational study that investigated sleep quality in people with low back pain. People with low back pain were recruited from primary care and the community. Sleep quality was measured with subjective (self-report) and objective (polysomnography (PSG)) measures. PSG analysis classifies sleep into stages, of which slow-wave sleep (SWS) is thought to have a key role in maintaining or increasing pain intensity. We drew directed acyclic graphs to identify possible confounders of the relationship between both measures of sleep quality, and pain intensity. We constructed two linear regression models to explore the effect of subjective and objective sleep quality on next-day pain intensity before and after confounder adjustment. Results Thirty-nine participants were included in the study. For participants with low back pain, self-reported better quality sleep β=−0.38 (95% CI −0.63 to −0.13), or spending a greater proportion of time in SWS β=−0.12 (95% CI −0.22 to −0.02) was associated with lower next day pain intensity. After confounder adjustment, the effect reduced and was no longer significant for either self-reported β=−0.18 (95% CI −0.46 to 0.10), or SWS β=−0.08 (95% CI −0.18 to 0.03). Conclusions Sleep quality, whether measured by self-report or proportion of time in SWS, was associated with next day pain intensity for people with low back pain. However, this relationship is likely to be confounded and therefore not likely to be causal.

Objectives The aim of this study was to examine how the “wait-and-see” recommendation affects adolescents’ understanding of their illness and symptoms and their care-seeking behavior. Methods This study included brief qualitative, semi-structured online interviews. Adolescents (age 10–19 years) with long-term knee pain, who had been recommended “wait-and-see” by their general practitioner (GP), were recruited via previous studies and social media. Two researchers conducted brief semi-structured interviews through Microsoft Teams. An interview guide with open questions was created prior to the interviews and updated as new questions emerged. The extracted data was transcribed and analyzed via a reflexive thematic approach in NVivo. Results Eight adolescents (mean age 17.8) with longstanding or recurrent knee pain (mean duration 3.5 years) were included. The analysis identified four main themes: (1) The perception of wait and see over time, (2) The GP’s acknowledgement and consideration, (3) experienced limitation from knee pain and (4) the importance of getting a diagnosis. The perception of “wait-and-see” approach changed from positive to negative when adolescents received the recommendation multiple times. Adolescents experienced frustration with their situation and a lack of consideration from their GP made them cautious about seeking additional care. Knee pain significantly limited the adolescents’ physical-and social activities. Receiving a diagnosis was important and helped adolescents dealing with their pain. Conclusions The connotation of wait-and-see changed from positive to negative for adolescents when receiving the recommendation multiple times. The participants felt getting a clinical diagnosis was a relief. Furthermore, the lack of consideration and acknowledgement from the GP plays an essential role in the adolescent’s understanding of their knee pain. Implications Recommending adolescents to “wait-and-see” multiple times in relation to their knee problems can lead adolescents experience frustration and a lack of consideration from their GP. It would be advisable for GPs to provide adolescents with a diagnosis as it can facilitate them in dealing with their pain and to use simple language when explaining adolescents their condition to improve communication.

Objectives Opioids are commonly used to manage pain, despite an increased risk of adverse events and complications when used against recommendations. This register study uses data of osteoarthritis (OA) patients with joint replacement surgery to identify and characterize problematic opioid use (POU) prescription patterns. Methods The study population included adult patients diagnosed with OA in specialty care undergoing joint replacement surgery in Denmark, Finland, Norway, and Sweden during 1 January 2011 to 31 December 2014. Those with cancer or OA within three years before the first eligible OA diagnosis were excluded. Patients were allocated into six POU cohorts based on dose escalation, frequency, and dosing of prescription opioids post-surgery (definitions were based on guidelines, previous literature, and clinical experience), and matched on age and sex to patients with opioid use, but not in any of the six cohorts. Data on demographics, non-OA pain diagnoses, cardiovascular diseases, psychiatric disorders, and clinical characteristics were used to study patient characteristics and predictors of POU. Results 13.7% of patients with OA and a hip/knee joint replacement were classified as problematic users and they had more comorbidities and higher pre-surgery doses of opioids than matches. Patients dispensing high doses of opioids pre-surgery dispensed increased doses post-surgery, a pattern not seen among patients prescribed lower doses pre-surgery. Being dispensed 1–4,500 oral morphine equivalents in the year pre-surgery or having a non-OA pain diagnosis was associated with post-surgery POU (OR: 1.44–1.50, and 1.11–1.20, respectively). Conclusions Based on the discovered POU predictors, the study suggests that prescribers should carefully assess pain management strategies for patients with a history of comorbidities and pre-operative, long-term opioid use. Healthcare units should adopt risk assessment tools and ensure that these patients are followed up closely. The data also demonstrate potential areas for further exploration in improving patient outcomes and trajectories.

Objectives There are several known predictors of pain after total knee arthroplasty (TKA). However, it is unclear whether acute postoperative pain intensity and postoperative opioid intake are associated with pain 12 months after TKA. Thus, the aim of this study was to assess whether worst pain intensity and opioid intake during the early postoperative period are associated with moderate-severe pain 12 months after TKA. Methods A total of 202 patients undergoing primary TKA between October 2012 and September 2014 were prospectively enrolled. Age, sex, contralateral knee pain, BMI, physical status and opioid intake were collected preoperatively. Ketamine and daily opioid intake were collected on postoperative days (POD) 0–3. Using the Brief Pain Inventory, patients’ “worst pain intensity” was measured preoperatively, on POD 0–4, and 12 months after TKA. Two logistic regression models evaluated the independent association of early postoperative pain intensity (model 1) and postoperative opioid intake (model 2) with moderate-severe pain 12 months after TKA, adjusting for possible confounders. Results In total, 187 patients with data at the 12 month postoperative follow-up were included in this analysis. Pain intensity on POD2 and POD3, as well as preoperative pain and BMI, were significantly associated with pain at 12 months in univariate models. However, in multivariable models adjusted for preoperative pain and BMI, neither pain intensity on POD 0–4 (model 1) nor opioid intake on POD 0–3 (model 2) were associated with pain at 12 months. Preoperative pain was still significant in both models, but BMI remained significant only in model 2. Conclusions Worst pain intensity and opioid intake during the early postoperative period were not associated with moderate-severe pain 12 months after TKA when controlling for potential confounders. More research is needed to confirm these findings.

Objectives Gender has been suggested to play a critical role in how facial expressions of pain are perceived by others. With the present study we aim to further investigate how gender might impact the decoding of facial expressions of pain, (i) by varying both the gender of the observer as well as the gender of the expressor and (ii) by considering two different aspects of the decoding process, namely intensity decoding and pain recognition. Methods In two online-studies, videos of facial expressions of pain as well as of anger and disgust displayed by male and female avatars were presented to male and female participants. In the first study, valence and arousal ratings were assessed (intensity decoding) and in the second study, participants provided intensity ratings for different affective states, that allowed for assessing intensity decoding as well as pain recognition. Results The gender of the avatar significantly affected the intensity decoding of facial expressions of pain, with higher ratings (arousal, valence, pain intensity) for female compared to male avatars. In contrast, the gender of the observer had no significant impact on intensity decoding. With regard to pain recognition (differentiating pain from anger and disgust), neither the gender of the avatar, nor the gender of the observer had any affect. Conclusions Only the gender of the expressor seems to have a substantial impact on the decoding of facial expressions of pain, whereas the gender of the observer seems of less relevance. Reasons for the tendency to see more pain in female faces might be due to psychosocial factors (e.g., gender stereotypes) and require further research.

Objectives Existing equipment for quantitative sensory testing is generally expensive and not easily applicable in a clinical setting thus simple bed-side devices are warranted. Pressure hyperalgesia is a common finding in patients with musculoskeletal pain and an experimental model is delayed-onset muscle soreness (DOMS). DOMS is characterised by muscle hyperalgesia and some studies report facilitation of temporal summation of pain. This study aimed to detect DOMS induced muscle hyperalgesia and temporal summation of pain using a newly developed bed-side quantitative sensory testing device to deliver standardised pressure. Methods Twenty-two healthy participants participated in two sessions with the second session approximately 48 h after baseline. Pressure pain intensities were assessed from the gastrocnemius muscle with four probes calibrated to apply 2, 4, 6 and 8 kg, respectively. Temporal summation of pain (10 stimuli delivered at 0.5 Hz using the 6 kg probe) intensities were assessed from the same location. DOMS was evoked in the gastrocnemius muscle by an eccentric exercise. Sleepiness and physical activity were measured with the Epworth Sleepiness Scale and the Global Physical Activity Questionnaire to investigate if they were associated with the quantitative sensory testing measures. Results Pressure pain intensity was significantly increased 48 h after induction of DOMS when compared to baseline for all four probes (p<0.05). Temporal summation of pain was not statistically significant affected by DOMS and sleep quality and physical activity did not associate with any of the measures. Conclusions This study introduces a simple, bed-side assessment tool for the assessment of pressure pain intensity and hence hyperalgesia and temporal summation of pain.

Objectives Previous research on stress-induced pain modulation suggests that moderate psychological stress usually leads to hyperalgesia while more severe threat results in hypoalgesia. However, existing studies often lack suitable control conditions imperative to identify mere stress effects. Similarly, research mainly focused on pure anticipation of a social threat, not taking into consideration actual experiences of social evaluation. Therefore, we set out to investigate actual social up- and downgrading combined with a standardized stress paradigm to evaluate short-term and prolonged changes in pain perception and their potential association with neuroendocrine and subjective stress parameters. Methods We allocated 177 healthy women to four experimental conditions, either the standard version of the Trier Social Stress Test (TSST) followed by positive, negative or no performance feedback, or a well-matched but less demanding placebo version of the TSST. Stress responses were assessed with ratings, salivary alpha-amylase, and salivary cortisol. To capture putative effects of stress on pain, heat pain threshold, ratings of phasic heat pain stimuli, and conditioned pain modulation were measured. Results Despite a largely successful stress induction, results do not support a reliable influence of experimentally induced social stress–with or without subsequent performance feedback–on pain in women. Further, we found no clear association of pain modulation and changes in neuroendocrine or subjective stress responses. Conclusions Our results contrast previous studies, which repeatedly demonstrated stress-induced hypo- or hyperalgesia. This might be due to methodological reasons as former research was often characterized by high heterogeneity regarding the applied stressors, low sample sizes, and lacking or inconclusive control conditions. Thus, our results raise the question whether pain modulation in women by experimental psychosocial stress might have been overestimated in the past. Future research is necessary, which should employ parametric stress induction methods including well-matched control tasks, taking into consideration the participants’ gender/sex and the time course of the stress response relative to pain assessment. The study is registered as DRKS00026946 at ‘Deutsches Register Klinischer Studien’ (DRKS) and can be also found at the World Health Organization’s search portal.

Objectives Patient and stakeholder engagements in research have increasingly gained attention in healthcare and healthcare-related research. A common and rigorous approach to establish research priorities based on input from people and stakeholders is the James Lind Alliance Priority Setting Partnership (JLA-PSP). The aim of this study was to establish research priorities for chronic musculoskeletal (MSK) pain by engaging with people living with chronic MSK pain, relatives to people living with chronic MSK pain, healthcare professionals (HCP), and researchers working with chronic MSK pain. Methods This JLA-PSP included a nation-wide survey in Denmark, an interim prioritisation, and an online consensus building workshop. The information gained from this was the basis for developing the final list of specific research priorities within chronic MSK pain. Results In the initial survey, 1010 respondents (91% people living with chronic MSK pain/relatives, 9% HCPs/researchers) submitted 3121 potential questions. These were summarised into 19 main themes and 36 sub-themes. In the interim prioritisation exercise, 51% people living with pain/relatives and 49% HCPs/researchers reduced the list to 33 research questions prior to the final priority setting workshop. 23 participants attended the online workshop (12 people/relatives, 10 HCPs, and 1 researcher) who reached consensus for the most important research priorities after two rounds of discussion of each question. Conclusions This study identified several specific research questions generated by people living with chronic MSK pain, relatives, HCPs, and researchers. The stakeholders proposed prioritization of the healthcare system’s ability to support patients, focus on developing coherent pathways between sectors and education for both patients and HCP. These research questions can form the basis for future studies, funders, and be used to align research with end-users’ priorities.

Background Mouth pain has been associated with abnormal vitamin B6 levels. Hypophosphatasia is a rare genetic disease, which causes imbalances between B6 vitamers. We report the case of a patient with hypophosphatasia and burning mouth pain. Case presentation A 39-year old Caucasian male with chronic burning mouth pain underwent extensive investigations with no cause of the pain being found. During the course of the investigation, an elevated vitamin B6 (pyridoxal phosphate) level was detected, which led to the diagnosis of hypophosphatasia. We hypothesize that the patient’s mouth pain stems from hypophosphatasia through a B6 dependent mechanism. Conclusions Mouth pain may, in some cases, be a symptom of hypophosphatasia and when investigating B6 in relation to mouth pain, attention should be paid to the exact B6 vitamer measured. The case underlines the importance of low alkaline phosphatase results, especially in patients with unexplained pain, as this should prompt suspicion of hypophosphatasia.

Objectives There appears to be an unwarranted focus on all chronic pain being a “chronification” of acute pain. Despite a plethora of studies on mechanisms to prevent this “chronification” following surgery, the positive effects have been minimal. An alternate model to explain chronic pain is presented. Methods Research in PUBMED and accessing data from the HUNTpain examination study. Results Data from the HUNT pain examination study reveal that less than 25% of individuals with chronic pain in a general population can relate the onset to an acute event. Another theory explaining the origin of chronic pain is that of priming and the accumulation of events that can be predictors along a continuum before chronic pain is apparent. This theory is presented to refocus for better prevention and treatment of chronic pain. Conclusions “Chronification” cannot explain all cases of chronic/persistent pain. The plastic changes in the pain processing system can be seen as a continuum where at some point where an acute pain event is only one of several possible tipping points on this continuum that changes potential pain to perceived pain.

Objectives Patients with Korsakoff syndrome (KS) may have a diminished pain perception. Information on KS and pain is scarce and limited to case descriptions. The present study is the first to investigate the underlying neural mechanisms of altered pain perception in patients with KS more systematically. Methods We conducted a literature search on neural correlates of pain perception in other neurocognitive disorders in which extensive research was done. Results The brain areas that are affected in KS showed considerable overlap with the neural correlates of pain perception in other neurocognitive disorders. We discussed which different aspects of disturbed pain perception could play a role within KS, based on distinct neural damage and brain areas involved in pain perception. Conclusions Combining current knowledge, we hypothesize that diminished pain perception in KS may be related to lesioned neural connections between cerebral cortical networks and relays of mainly the thalamus, the periaqueductal gray, and possibly lower brain stem regions projecting to the cerebellum. Based on these neural correlates of altered pain perception, we assume that increased pain thresholds, inhibition of pain signals, and disturbed input to cerebral and cerebellar cortical areas involved in pain processing, all are candidate mechanisms in cases of diminished pain perception in KS. We recommend that clinicians need to be alert for somatic morbidity in patients with KS. Due to altered neural processing of nociceptive input the clinical symptoms of somatic morbidity may present differently (i.e. limited pain responses) and therefore are at risk of being missed.