Healthy women show more experimentally induced central sensitization compared with men.

ABSTRACT: Women more often experience chronic pain conditions than men. Central sensitization (CS) is one key mechanism in chronic pain that can differ between the sexes. It is unknown whether CS processes are already more pronounced in healthy women than in men. In 66 subjects (33 women), a thermal CS induction protocol was applied to the dorsum of one foot and a sham protocol to the other. Spatial extent [cm 2 ] of secondary mechanical hyperalgesia (SMH) and dynamic mechanical allodynia were assessed as subjective CS proxy measures, relying on verbal feedback. Changes in nociceptive withdrawal reflex magnitude (NWR-M) and response rate (NWR-RR) recorded through surface electromyography at the biceps and rectus femoris muscles were used as objective CS proxies. The effect of the CS induction protocol on SMH was higher in women than in men (effect size 2.11 vs 1.68). Nociceptive withdrawal reflex magnitude results were statistically meaningful for women (effect size 0.31-0.36) but not for men (effect size 0.12-0.29). Differences between men and women were not meaningful. Nociceptive withdrawal reflex response rate at the rectus femoris increased in women after CS induction and was statistically different from NWR-RR in men (median differences of 13.7 and 8.4% for 120 and 140% reflex threshold current). The objective CS proxy differences indicate that dorsal horn CS processes are more pronounced in healthy women. The even larger sex differences in subjective CS proxies potentially reflect greater supraspinal influence in women. This study shows that sex differences are present in experimentally induced CS in healthy subjects, which might contribute to women's vulnerability for chronic pain.

Personalized assessment and management of non-specific low back pain.

BACKGROUND AND OBJECTIVE: Low back pain (LBP), and in particular non-specific low back pain (NSLBP), which accounts for approximately 90% of LBP, is the leading cause of years lived with disability worldwide. In clinical trials, LBP is often poorly categorized into 'specific' versus 'non-specific' and 'acute' versus 'chronic' pain. However, a better understanding of the underlying pain mechanisms might improve study results and reduce the number of NSLBP patients. DATABASES AND DATA TREATMENT: Narrative review. RESULTS: NSLBP is a multi-dimensional, biopsychosocial condition that requires all contributing dimensions to be assessed and prioritized. Thereby, the assessment of the contribution of nociceptive, neuropathic and nociplastic pain mechanisms forms the basis for personalized management. In addition, psychosocial (e.g. anxiety, catastrophizing) and contextual factors (e.g. work situation) as well as comorbidities need to be assessed and individually weighted. Personalized treatment of NSLBP further requires individually choosing treatment modalities, for example, exercising, patient education, cognitive-behavioural advice, pharmacotherapy, as well as tailoring treatment within these modalities, for example, the delivery of tailored psychological interventions or exercise programs. As the main pain mechanism and psychosocial factors may vary over time, re-assessment is necessary and treatment success should ideally be assessed quantitatively and qualitatively. CONCLUSIONS: The identification of the main contributing pain mechanism and the integration of the patients' view on their condition, including beliefs, preferences, concerns and expectations, are key in the personalized clinical management of NSLBP. In research, particular importance should be placed on accurate characterization of patients and on including outcomes relevant to the individual patient. SIGNIFICANCE STATEMENT: Here, a comprehensive review of the challenges associated with the diagnostic label 'non-specific low back pain' is given. It outlines what is lacking in current treatment guidelines and it is summarized what is currently known with respect to individual phenotyping. It becomes clear that more research on clinically meaningful subgroups is needed to best tailor treatment approaches.

Sensory phenotypes in complex regional pain syndrome and chronic low back pain-indication of common underlying pathomechanisms.

Introduction: First-line pain treatment is unsatisfactory in more than 50% of chronic pain patients, likely because of the heterogeneity of mechanisms underlying pain chronification. Objectives: This cross-sectional study aimed to better understand pathomechanisms across different chronic pain cohorts, regardless of their diagnoses, by identifying distinct sensory phenotypes through a cluster analysis. Methods: We recruited 81 chronic pain patients and 63 age-matched and sex-matched healthy controls (HC). Two distinct chronic pain cohorts were recruited, ie, complex regional pain syndrome (N = 20) and low back pain (N = 61). Quantitative sensory testing (QST) was performed in the most painful body area to investigate somatosensory changes related to clinical pain. Furthermore, QST was conducted in a pain-free area to identify remote sensory alterations, indicating more widespread changes in somatosensory processing. Results: Two clusters were identified based on the QST measures in the painful area, which did not represent the 2 distinct pain diagnoses but contained patients from both cohorts. Cluster 1 showed increased pain sensitivities in the painful and control area, indicating central sensitization as a potential pathomechanism. Cluster 2 showed a similar sensory profile as HC in both tested areas. Hence, either QST was not sensitive enough and more objective measures are needed to detect sensitization within the nociceptive neuraxis or cluster 2 may not have pain primarily because of sensitization, but other factors such as psychosocial ones are involved. Conclusion: These findings support the notion of shared pathomechanisms irrespective of the pain diagnosis. Conversely, different mechanisms might contribute to the pain of patients with the same diagnosis.

Spinal mobilization force-time characteristics: A scoping literature review.

BACKGROUND: Spinal mobilization (SMob) is often included in the conservative management of spinal pain conditions as a recommended and effective treatment. While some studies quantify the biomechanical (kinetic) parameters of SMob, interpretation of findings is difficult due to poor reporting of methodological details. The aim of this study was to synthesise the literature describing force-time characteristics of manually applied SMob. METHODS: This study is reported in accordance with the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) statement. Databases were searched from inception to October 2022: MEDLINE (Ovid), Embase, CINAHL, ICL, PEDro and Cochrane Library. Data were extracted and reported descriptively for the following domains: general study characteristics, number of and characteristics of individuals who delivered/received SMob, region treated, equipment used and force-time characteristics of SMob. RESULTS: There were 7,607 records identified and of these, 36 (0.5%) were included in the analysis. SMob was delivered to the cervical spine in 13 (36.1%), the thoracic spine in 3 (8.3%) and the lumbopelvic spine in 18 (50.0%) studies. In 2 (5.6%) studies, spinal region was not specified. For SMob applied to all spinal regions, force-time characteristics were: peak force (0-128N); duration (10-120s); frequency (0.1-4.5Hz); and force amplitude (1-102N). CONCLUSIONS: This study reports considerable variability of the force-time characteristics of SMob. In studies reporting force-time characteristics, SMob was most frequently delivered to the lumbar and cervical spine of humans and most commonly peak force was reported. Future studies should focus on the detailed reporting of force-time characteristics to facilitate the investigation of clinical dose-response effects.

BackWards - Unveiling the brain's topographic organization of paraspinal sensory input.

Cortical reorganization and its potential pathological significance are being increasingly studied in musculoskeletal disorders such as chronic low back pain (CLBP) patients. However, detailed sensory-topographic maps of the human back are lacking, and a baseline characterization of such representations, reflecting the somatosensory organization of the healthy back, is needed before exploring potential sensory map reorganization. To this end, a novel pneumatic vibrotactile stimulation method was used to stimulate paraspinal sensory afferents, while studying their cortical representations in unprecedented detail. In 41 young healthy participants, vibrotactile stimulations at 20 Hz and 80 Hz were applied bilaterally at nine locations along the thoracolumbar axis while functional magnetic resonance imaging (fMRI) was performed. Model-based whole-brain searchlight representational similarity analysis (RSA) was used to investigate the organizational structure of brain activity patterns evoked by thoracolumbar sensory inputs. A model based on segmental distances best explained the similarity structure of brain activity patterns that were located in different areas of sensorimotor cortices, including the primary somatosensory and motor cortices and parts of the superior parietal cortex, suggesting that these brain areas process sensory input from the back in a "dermatomal" manner. The current findings provide a sound basis for testing the "cortical map reorganization theory" and its pathological relevance in CLBP.

Spinal manipulation characteristics: a scoping literature review of force-time characteristics.

BACKGROUND: Spinal manipulation (SM) is a recommended and effective treatment for musculoskeletal disorders. Biomechanical (kinetic) parameters (e.g. preload/peak force, rate of force application and thrust duration) can be measured during SM, quantifying the intervention. Understanding these force-time characteristics is the first step towards identifying possible active ingredient/s responsible for the clinical effectiveness of SM. Few studies have quantified SM force-time characteristics and with considerable heterogeneity evident, interpretation of findings is difficult. The aim of this study was to synthesise the literature describing force-time characteristics of manual SM. METHODS: This scoping literature review is reported following the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) statement. Databases were searched from inception to October 2022: MEDLINE (Ovid), Embase, CINAHL, ICL, PEDro and Cochrane Library. The following search terms and their derivatives were adapted for each platform: spine, spinal, manipulation, mobilization or mobilisation, musculoskeletal, chiropractic, osteopathy, physiotherapy, naprapathy, force, motor skill, biomechanics, dosage, dose-response, education, performance, psychomotor, back, neck, spine, thoracic, lumbar, pelvic, cervical and sacral. Data were extracted and reported descriptively for the following domains: general study characteristics, number of and characteristics of individuals who delivered/received SM, region treated, equipment used and force-time characteristics of SM. RESULTS: Of 7,607 records identified, 66 (0.9%) fulfilled the eligibility criteria and were included in the analysis. Of these, SM was delivered to the cervical spine in 12 (18.2%), the thoracic spine in 40 (60.6%) and the lumbopelvic spine in 19 (28.8%) studies. In 6 (9.1%) studies, the spinal region was not specified. For SM applied to all spinal regions, force-time characteristics were: preload force (range: 0-671N); peak force (17-1213N); rate of force application (202-8700N/s); time to peak thrust force (12-938ms); and thrust duration (36-2876ms). CONCLUSIONS: Considerable variability in the reported kinetic force-time characteristics of SM exists. Some of this variability is likely due to differences in SM delivery (e.g. different clinicians) and the measurement equipment used to quantify force-time characteristics. However, improved reporting in certain key areas could facilitate more sophisticated syntheses of force-time characteristics data in the future. Such syntheses could provide the foundation upon which dose-response estimates regarding the clinical effectiveness of SM are made.

Lunar and mars gravity induce similar changes in spinal motor control as microgravity.

Introduction: Once more, plans are underway to send humans to the Moon or possibly even to Mars. It is therefore, important to know potential physiological effects of a prolonged stay in space and to minimize possible health risks to astronauts. It has been shown that spinal motor control strategies change during microgravity induced by parabolic flight. The way in which spinal motor control strategies change during partial microgravity, such as that encountered on the Moon and on Mars, is not known. Methods: Spinal motor control measurements were performed during Earth, lunar, Mars, and micro-gravity conditions and two hypergravity conditions of a parabola. Three proxy measures of spinal motor control were recorded: spinal stiffness of lumbar L3 vertebra using the impulse response, muscle activity of lumbar flexors and extensors using surface electromyography, and lumbar curvature using two curvature distance sensors placed at the upper and lower lumbar spine. The participants were six females and six males, with a mean age of 33 years (standard deviation: 7 years). Results: Gravity condition had a statistically significant (Friedmann tests) effect spinal stiffness (p < 0.001); on EMG measures (multifidus (p = 0.047), transversus abdominis (p < 0.001), and psoas (p < 0.001) muscles) and on upper lumbar curvature sensor (p < 0.001). No effect was found on the erector spinae muscle (p = 0.063) or lower curvature sensor (p = 0.170). Post hoc tests revealed a significant increase in stiffness under micro-, lunar-, and Martian gravity conditions (all p's < 0.034). Spinal stiffness decreased under both hypergravity conditions (all p's ≤ 0.012) and decreased during the second hypergravity compared to the first hypergravity condition (p = 0.012). Discussion: Micro-, lunar-, and Martian gravity conditions resulted in similar increases in spinal stiffness, a decrease in transversus abdominis muscle activity, with no change in psoas muscle activity and thus modulation of spinal motor stabilization strategy compared to those observed under Earth's gravity. These findings suggest that the spine is highly sensitive to gravity transitions but that Lunar and Martian gravity are below that required for normal modulation of spinal motor stabilization strategy and thus may be associated with LBP and/or IVD risk without the definition of countermeasures.

Intra- and inter-session reliability of electrical detection and pain thresholds of cutaneous and muscle primary afferents in the lower back of healthy individuals.

To advance evidence-based practice and targeted treatments of low back pain (LBP), a better pathophysiological understanding and reliable outcome measures are required. The processing of nociceptive information from deeper somatic structures (e.g., muscle, fascia) might play an essential role in the pathophysiology of LBP. In this study, we measured the intra- and inter-session reliability of electrical detection and pain thresholds of cutaneous and muscle primary afferents of the lower back. Twenty healthy participants attended two study visits separated by 27.7 ± 1.7 days. To determine the location-specific electrical detection threshold (EDT) and pain threshold (EPT), needle electrodes were inserted in the epidermal layer over, and in the lumbar erector spinae muscle. Additionally, established quantitative sensory testing (QST) parameters were assessed. Reliability was determined by differences between measurements, intraclass correlation coefficients (ICC2,1), Bland-Altman plots, and standard error of measurement (SEM). Correspondence between QST parameters and electrical thresholds was assessed using Pearson's correlation. Except for cutaneous EPT, no significant (p ≤ 0.05) intra- and inter-session differences were observed. Excellent intra-session reliability was shown for cutaneous and intramuscular electrical stimulations and all QST parameters (ICC: 0.76-0.93). Inter-session reliabilities were good (ICC: 0.74-0.75) except for electrical stimulations (ICC: 0.08-0.36). Limits of agreement and SEM were higher for inter-session than intra-session. A medium to strong relationship was found between electrical and mechanical/pressure pain thresholds. In conclusion, cutaneous and intramuscular electrical stimulation will potentially close an important diagnostic gap regarding the selective examination of deep tissue afferents and provide location-specific information for the excitability of non-nociceptive and nociceptive afferents.

Development of a computerized 2D rating scale for continuous and simultaneous evaluation of two dimensions of a sensory stimulus.

Introduction: One-dimensional rating scales are widely used in research and in the clinic to assess individuals' perceptions of sensory stimuli. Although these scales provide essential knowledge of stimulus perception, their limitation to one dimension hinders our understanding of complex stimuli. Methods: To allow improved investigation of complex stimuli, a two-dimensional scale based on the one-dimensional Gracely Box Scale was developed and tested in healthy participants on a visual and an auditory task (rating changes in brightness and size of circles and rating changes in frequency and sound pressure of sounds, which was compared to ratings on one-dimensional scales). Before performing these tasks, participants were familiarized with the intensity descriptors of the two-dimensional scale by completing two tasks. First, participants sorted the descriptors based on their judgment of the intensity of the descriptors. Second, participants evaluated the intensity of the descriptors by pressing a button for the duration they considered matching the intensity of the descriptors or squeezing a hand grip dynamometer as strong as they considered matching the intensity of the descriptors. Results: Results from these tasks confirmed the order of the descriptors as displayed on the original rating scale. Results from the visual and auditory tasks showed that participants were able to rate changes in the physical attributes of visual or auditory stimuli on the two-dimensional scale as accurately as on one-dimensional scales. Discussion: These results support the use of a two-dimensional scale to simultaneously report multiple dimensions of complex stimuli.

Central sensitization in CRPS patients with widespread pain: a cross-sectional study.

OBJECTIVE: Widespread pain hypersensitivity and enhanced temporal summation of pain (TSP) are commonly reported in patients with complex regional pain syndrome (CRPS) and discussed as proxies for central sensitization. This study aimed to directly relate such signs of neuronal hyperexcitability to the pain phenotype of CRPS patients. METHODS: Twenty-one CRPS patients and 20 healthy controls (HC) were recruited. The pain phenotype including spatial pain extent (assessed in % body surface) and intensity were assessed and related to widespread pain hypersensitivity, TSP, and psychological factors. Quantitative sensory testing (QST) was performed in the affected, the contralateral and a remote (control) area. RESULTS: CRPS patients showed decreased pressure pain thresholds in all tested areas (affected: t(34) = 4.98, P < .001, contralateral: t(35) = 3.19, P = .005, control: t(31) = 2.65, P = .012). Additionally, patients showed increased TSP in the affected area (F(3,111) = 4.57, P = .009) compared to HC. TSP was even more enhanced in patients with a high compared to a low spatial pain extent (F(3,51) = 5.67, P = .008), suggesting pronounced spinal sensitization in patients with extended pain patterns. Furthermore, the spatial pain extent positively correlated with the Bath Body Perception Disturbance Scale (ρ = 0.491; P = .048). CONCLUSIONS: Overall, we provide evidence that the pain phenotype in CRPS, that is, spatial pain extent, might be related to sensitization mechanism within the central nociceptive system. This study points towards central neuronal excitability as a potential therapeutic target in patients with more widespread CRPS.

Evidence for dopaminergic involvement in endogenous modulation of pain relief.

Relief of ongoing pain is a potent motivator of behavior, directing actions to escape from or reduce potentially harmful stimuli. Whereas endogenous modulation of pain events is well characterized, relatively little is known about the modulation of pain relief and its corresponding neurochemical basis. Here, we studied pain modulation during a probabilistic relief-seeking task (a 'wheel of fortune' gambling task), in which people actively or passively received reduction of a tonic thermal pain stimulus. We found that relief perception was enhanced by active decisions and unpredictability, and greater in high novelty-seeking trait individuals, consistent with a model in which relief is tuned by its informational content. We then probed the roles of dopaminergic and opioidergic signaling, both of which are implicated in relief processing, by embedding the task in a double-blinded cross-over design with administration of the dopamine precursor levodopa and the opioid receptor antagonist naltrexone. We found that levodopa enhanced each of these information-specific aspects of relief modulation but no significant effects of the opioidergic manipulation. These results show that dopaminergic signaling has a key role in modulating the perception of pain relief to optimize motivation and behavior.

Typical Cockpit Ergonomics Influence on Cervical Motor Control in Healthy Young Male Adults.

INTRODUCTION: Neck pain and injury are common problems in military high-performance aircraft and helicopter aircrews. A contributing factor may be the reclined sitting position in cockpits. This study aimed to determine the effect of typical cockpit ergonomics on cervical proprioception, assessed by using the cervical joint position error (cJPE).METHODS: A total of 49 healthy male military employees (mean age 19.9 ± 2.2 yr) were examined. Measurements of the cJPE were obtained in the flexion, extension, and rotation directions in an upright and in a 30°-reclined sitting position. Each condition comprised three trials, with an additional 3-kg head load to mimic real world working conditions.RESULTS: A smaller cJPE was noted in the 30°-reclined sitting position (mean cJPE = 3.9 cm) than in the upright sitting position (mean cJPE = 4.6 cm) in the flexion direction. The cJPE decreased significantly in all movement directions across the three trials; for example, in the flexion direction in the 30°-reclined sitting position: Trial 1/2/3 mean cJPE = 5.0/3.8/3.1 cm.CONCLUSION: It seems that a reclined seating position has a positive influence on cJPE. However, the result is weak. In both sitting positions and all three directions, the first tests of the cJPE showed the highest values. Already after one or two further measurement runs, a significantly reduced cJPE was observed. This rapid improvement might indicate that an exercise similar to the cJPE test may improve the pilots' cervical proprioception and possibly reduce the risk of injury or pain.Heggli U, Swanenburg J, Hofstetter L, Häusler M, Schweinhardt P, Bron D. Typical cockpit ergonomics influence on cervical motor control in healthy young male adults. Aerosp Med Hum Perform. 2023; 94(3):107-112.

Self-reported attitudes, skills and use of evidence-based practice among Swiss chiropractors: a national survey.

STUDY OBJECTIVES: The high burden of disease associated with musculoskeletal disorders severely impacts patients' well-being. As primary care providers, Swiss chiropractors ought to contribute towards identifying and using effective treatment strategies. An established approach is the full integration of evidence-based practice (EBP). This study aimed to investigate the attitudes, skills and use of EBP among Swiss chiropractors, as well as investigating potential facilitators and barriers for its adoption. METHODS AND MATERIAL: All 329 members of the Swiss Association of Chiropractic (ChiroSuisse) were invited in March 2021 to participate in this cross-sectional survey. Data were acquired anonymously online, using the Evidence-Based practice Attitude and utilization SurvEy (EBASE). The survey encompassed 55 questions measuring attitudes (n = 8, response range 1-5; total score range of 8-40), skills (n = 13, response range 1-5; total score range of range of 13-65) and use of EBP (n = 6, response range 0-4; total score range of 0-24). RESULTS: 228 (69.3%) chiropractors returned complete EBASE questionnaires. This sample was representative of all ChiroSuisse members with respect to gender, age groups and proportion of chiropractic residents. Respondents generally held positive attitudes towards EBP, as indicated by the high mean (31.2) and median (31) attitude sub-score (range 11-40). Self-reported skills had a mean sub-score of 40.2 and median of 40 (range 13-65). Knowledge about EBP-based clinical practice had been primarily obtained in chiropractic under- or postgraduate education (33.8% and 26.3%, respectively). Use of EBP achieved a lower sub-score, with mean and median values of 7.4 and 6, respectively (range 0-24). The most commonly identified barriers preventing EBP uptake were lack of time (67.9%) and lack of clinical evidence in chiropractic/manual therapy-related health fields (45.1%). CONCLUSION: Swiss chiropractors held favourable attitudes and reported moderate to moderate-high skill levels in EBP. Nevertheless, similar to chiropractors in other countries, the self-reported use of EBP was relatively low, with lack of time and lack of clinical evidence being the most named barriers.

The influence of social signals on the self-experience of pain: A neuroimaging review.

Researchers in cognitive neuroscience have investigated extensively how psychological factors shape the processing and perception of pain using behavioral, physiological, and neuroimaging methods. However, social influences of pain, an essential part of biopsychosocial pain models, have received relatively little attention. This is particularly true for the neurobiological mechanisms underlying social modulations on pain. Therefore, this review discusses the findings of recent neuroimaging studies measuring the effects of social manipulations on pain perception (e.g., verbal and non-verbal social signals, social interaction style, conformity, social support, and sociocultural mediators). Finally, a schematic summary of the different social modulatory themes is presented.

Anti- and Pro-Nociceptive mechanisms in neuropathic pain after human spinal cord injury.

BACKGROUND: Deficient endogenous pain modulation and increased nociceptive excitability are key features of central sensitization and can be assessed in humans by conditioned pain modulation (CPM, anti-nociceptive) and temporal summation of pain (TSP, pro-nociceptive), respectively. This study aimed to investigate these measures as proxies for central sensitization in subjects with chronic neuropathic pain (NP) after spinal cord injury (SCI). METHODS: In paraplegic subjects with NP (SCI-NP; n = 17) and healthy controls (HC; n = 17), parallel and sequential sham-controlled CPM paradigms were performed using pressure pain threshold at the hand, that is, above lesion level, as test stimulus. The conditioning stimulus was a noxious cold (verum) or lukewarm water bath (sham) applied contralaterally. Regarding pro-nociceptive mechanisms, a TSP protocol with individually-adjusted pressure pain stimuli at the thenar eminence was used. CPM and TSP magnitudes were related to intensity and spatial extent of spontaneous NP. RESULTS: Neither the parallel nor sequential sham-controlled CPM paradigm showed any significant inhibition of above-level pressure pain thresholds for SCI-NP or HC. Accordingly, no group difference in CPM capacity was found, however, subjects with more intense spontaneous NP showed lower inhibitory CPM capacity. TSP was observed for both groups but was not enhanced in SCI-NP. CONCLUSIONS: Our results do not support altered above-level anti- or pro-nociceptive mechanisms in SCI-NP compared with HC; however, they also highlight the relevance of spontaneous NP intensity with regards to the capacity of endogenous pain modulation in SCI subjects. SIGNIFICANCE: Central sensitization encompasses deficient endogenous pain modulation and increased nociceptive excitability. These two mechanisms can be assessed in humans by conditioned pain modulation and temporal summation of pain, respectively. Our data demonstrates a lack of descending pain inhibition only in subjects with severe neuropathic pain which may hint towards central sensitization at spinal and/or supra-spinal levels. Disentangling the mechanisms of endogenous pain modulation and neuronal hyperexcitability might improve mechanism-based treatment of neuropathic pain in subjects with spinal cord injury.

No alteration of back muscle oxygenation during isometric exercise in individuals with non-specific low back pain.

The aim of our study was (I) To compare back muscle oxygenation and perfusion as well as Biering-Sorensen muscle endurance (BSME) test holding times between chronic non-specific low back pain (CNSLBP) patients and asymptomatic controls matched for age, body mass index (BMI), sex and physical activity, and (II) to investigate factors associated with BSME holding times. Muscle perfusion (tHb) and oxygenation (SmO2) were measured by near-infrared spectroscopy (NIRS) based oximetry in three back muscles during the BSME. Reliability of tHb and SmO2 was assessed in a separate sample. BSME holding time and SmO2 were compared between patients (n = 45) and controls (n = 45) and factors associated with BSME holding time were assessed using multiple linear regression. Reliability for SmO2 was excellent (ICC = 0.87-0.99). THb showed poor to moderate reliability and was not further used. Groups differed for BSME holding time (P = 0.03), pain intensity (P ≤ 0.0005) and subcutaneous tissue thickness (P = 0.01) but not for NIRS measures. Physical activity and BMI were associated with BSME holding times. Insufficient muscle oxygenation does not seem to be a major factor contributing to CNSLBP. Future investigation should evaluate other determinants of BSME holding times, such as motivation and recruitment of auxiliary muscles.

Limited prognostic value of pain duration in non-specific neck pain patients seeking chiropractic care.

BACKGROUND: Pain chronicity is considered an important prognostic factor for outcome. Here, it was investigated whether pain duration influences outcome when only chronic patients (pain >3 months) are considered. Secondary aims were to determine, in patients of any pain duration, how much variance in outcome is explained by pain duration and whether pain duration truly predicts outcomes, that is out-of-sample prediction in independent data. METHODS: Secondary analysis of a cohort study of neck pain patients. Patients were assessed before start of treatment and at 1-week, 1-, 3-, 6- and 12-month follow-up. Outcomes were patient global impression of change (PGIC) and percent change in patients' perceived pain intensity, rated on a numerical rating scale (NRS). Regression analyses (linear and logistic) and supervised machine learning were used to test the influence of pain duration on PGIC and percent NRS change at 1-week, 1-, 3-, 6- and 12-month follow-up within sample and out-of-sample. Separate analyses were performed for the full sample (n = 720) and for chronic patients (n = 238) only. RESULTS: No relationship between pain duration and outcome was found for chronic patients only. For the full sample, statistical relationships between pain duration and outcomes were observed at all tested follow-up time points. However, the amount of variance in outcome explained by pain duration was low and no out-of-sample prediction was possible. CONCLUSIONS: Pain duration did not emerge as an important predictor of outcome in this database of 720 neck pain patients receiving chiropractic treatment. SIGNIFICANCE STATEMENT: The relatively large dataset of neck pain patients challenges the widely accepted wisdom that pain duration is an important predictor of pain outcomes and that very chronic patients might only have a small likelihood of getting better. It is postulated that these results are important for the attitude of the first encounter between healthcare professionals and chronic patients.

Neural and behavioral correlates of human pain avoidance in participants with and without episodic migraine.

ABSTRACT: The innate motivation to avoid pain can be disrupted when individuals experience uncontrollable stress, such as pain. This can lead to maladaptive behaviors, including passivity, and negative affect. Despite its importance, motivational aspects of pain avoidance are understudied in humans and their neural mechanisms vastly unknown. Rodent models suggest an important role of the periaqueductal gray, but it is unknown whether it subserves a similar role in humans. Furthermore, it is unclear whether pain avoidance is associated with individual differences in pain coping. Using functional magnetic resonance imaging, networks underlying pain avoidance behavior were examined in 32 participants with and without episodic migraine. Pain avoidance behavior was assessed using an adaptation of the incentive delay task. In each trial of the task, participants tried to avoid a painful stimulus and receive a nonpainful one instead while the difficulty to succeed varied across trials (3 difficulty levels: safe, easy, and difficult). After unsuccessful pain avoidance on the preceding trial, participants showed reduced pain avoidance behavior, especially in the difficult condition. This reduction in behavior was associated with higher helplessness scores only in participants with migraine. Higher helplessness in participants with migraine was further correlated with a stronger decrease in activation of cortical areas associated with motor behavior, attention, and memory after unsuccessful pain avoidance. Of these areas, specifically posterior parietal cortex activation predicted individual's pain avoidance behavior on the next trial. The results link individual pain coping capacity to patterns of neural activation associated with altered pain avoidance in patients with migraine.

Endogenous opioids contribute to the feeling of pain relief in humans.

Endogenous opioids mediate the pleasurable responses to positively reinforcing stimuli such as palatable food. Yet, the reduction or omission of a negative experience can also be rewarding (negative reinforcement). As such, pain relief leads to negative reinforcement and evokes a pleasant feeling in humans. Although it has been shown that the feeling of pleasure associated with positive reinforcement is at least partly mediated through endogenous opioids, it is currently unknown whether similar neurochemical mechanisms are involved in the pleasant feeling evoked by pain relief. In this study, 27 healthy participants completed 2 identical experimental sessions, 1 with placebo and 1 with naltrexone, an endogenous opioid antagonist. Pain relief was induced by superficial cooling after heat stimulation of capsaicin-sensitized skin. Participants rated the relief and pleasantness in response to the cooling. Endogenous opioid blockade by naltrexone decreased relief and pleasantness ratings compared with placebo (P = 0.0027). This study provides evidence that endogenous opioids play a role in mediating the pleasant feeling of pain relief in humans. Clinically, the rewarding nature of pain relief and its underlying mechanisms require consideration because of their potential reinforcing effects on behaviors that might be beneficial short-term but maladaptive long-term.