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We developed a novel, wearable system that couples motion sensing and electrical stimulation in real-time to study motor adaptation in new environments. In two experiments we established key information needed in the development of our system including 1) pain habituation patterns and motor adaptations to knee pain while walking; 2) a model of electrical stimulation magnitude as a function of pain perception; and 3) gait-phase-dependent modulation of pain intensity. Over three 10-minute walking bouts, we observed significant pain habituation (p1/10, though a piecewise linear (Adj R $^{{2}} =0.874$ ) or exponential model (Adj R $^{{2}} =0.869$ ) was required to fit the perception data across the stimulus intensity range (0-5/10). Finally, participants did not report gait-phase-dependent modulation of pain intensity while walking with tonic electrical stimulation. Our wearable system supports new motor adaptation experiments in novel contexts not previously possible. These results show the system induces localized pain perceptions and motor adaptations in complex movements (walking) while providing guidelines to structure future experimental pain studies.

Introduction: This study investigated the variability in lumbar neuromuscular adaptations to pain, the task dependency of pain adaptations and the effect of these adaptations on motor performance. Methods: Twenty-four healthy participants performed isometric back extension contractions at 45° and 90° trunk flexion under pain-free and experimental low back pain conditions induced by electrical stimulation. High-density surface electromyography recorded lumbar muscle activation strategies, and force steadiness was measured using a load cell. Results: While considerable variability in neuromuscular adaptations to lumbar pain was observed among participants, consistent patterns were found between tasks. In the 90° trunk flexion position, both sides exhibited greater magnitudes of pain adaptations for muscle activity redistribution in the mediolateral axis (p < 0.05, 86% increase) and muscle activity amplitude (p < 0.001, 183% increase) compared to the 45° trunk flexion position. A significant negative correlation was found between the magnitude of the mediolateral spatial redistribution of muscle activity and force steadiness on the left side (p = 0.045). Discussion: These findings highlight the intricate and task-dependent nature of neuromuscular adaptations to pain within lumbar muscles, and points toward a potential trade-off between pain adaptations and performance. [ABSTRACT FROM AUTHOR]

People experiencing kinesiophobia are more likely to develop persistent disabilities and chronic pain. However, the impact of kinesiophobia on the motor system remains poorly understood. We investigated whether kinesiophobia could modulate shoulder pain-induced changes in (1) kinematic parameters and muscle activation during functional movement and (2) corticospinal excitability. Thirty healthy, pain-free subjects took part in the study. Shoulder, elbow, and finger kinematics, as well as electromyographic activity of the upper trapezius and anterior deltoid muscles, were recorded while subjects performed a pointing task before and during pain induced by capsaicin at the shoulder. Anterior deltoid cortical changes in excitability were assessed through the slope of transcranial magnetic stimulation input-output curves obtained before and during pain. Results revealed that pain reduced shoulder electromyographic activity and had a variable effect on finger kinematics, with individuals with higher kinesiophobia showing greater reduction in finger target traveled distance. Kinesiophobia scores were also correlated with the changes in deltoid corticospinal excitability, suggesting that the latter can influence motor activity as soon as the motor signal emerges. Taken together, these results suggest that pain and kinesiophobia interact with motor control adaptation. [ABSTRACT FROM AUTHOR]

Context: Interindividual variability in pain is modified by interactions of multiple biopsychosocial factors. Though there are reported findings on pain variability from studies around the world, the relationship between pain outcomes and anthropometric profiles remains unclear due to conflicting findings. Aim: This study was designed to investigate relationships between experimental pain outcomes and anthropometric profiles in a healthy Nigerian population. Materials and Methods: One hundred and sixty-one healthy volunteers aged 20 to 65 years were recruited for the study. Experimental pain was induced using cold pressor pain, pressure pain, and ischemic pain procedures. Results: We found that subjects with a normal body mass index (BMI) had a statistically significant higher ischemic pain tolerance than their obese counterparts. Right-handed participants had higher cold pressor pain thresholds than their left-handed counterparts, and the difference was statistically significant. Hb genotype and blood groups affected experimental pain outcomes. There was a statistically significant negative correlation between BMI and ischemic pain tolerance. Conclusion: We concluded that the association between BMI and experimental pain outcomes depends on the type of pain induction method used. Right-handedness appeared to be associated with increased cold pressor pain threshold. [ABSTRACT FROM AUTHOR]

Facial expressions of pain play an important role in pain diagnostics and social interactions. Given the prominent impact of sex on various aspects of pain, it is not surprising that sex differences have also been explored regarding facial expressions of pain; however, with inconclusive findings. We aim to further investigate sex differences in facial expressions of pain by using a large, combined sample to maximize statistical power. Data from 7 previous studies of our group were merged, combining in total the data of 392 participants (male: 192, female: 200). All participants received phasic heat pain, with intensities being tailored to the individual pain threshold. Pain intensity ratings were assessed, and facial responses were manually analyzed using the Facial Action Coding. To compare facial and subjective responses between sexes, linear mixed-effects models were used, with study ID as a random effect. We found significant sex differences in facial responses, with females showing elevated facial responses to pain, although they received lower physical heat intensities (women had lower pain thresholds). In contrast, pain intensity ratings did not differ between sexes. Additionally, facial and subjective responses to pain were significantly associated across sexes, with females showing slightly stronger associations. Although variations in facial expressions of pain are very large even within each sex, our findings demonstrate that women facially communicate pain more intensively and with a better match to their subjective experience compared with men. This indicates that women might be better in using facial communication of pain in an intensity-discriminative manner. [ABSTRACT FROM AUTHOR]

Summary Acute sleep deprivation in experimental studies has been shown to induce pain hypersensitivity in females. However, the impact of natural sleep deficiency and fluctuations across the week on pain perception remains unclear. A sleep‐monitoring headband and self‐reports were utilized to assess objective and subjective sleep in longer (> 6 hr) and short sleepers (< 6 hr). Pain sensitivity measures including heat, cold, pressure pain thresholds, pain inhibition (conditioned pain modulation) and facilitation (tonic pain summation) were assessed on Mondays and Fridays. Forty‐one healthy young (23.9 ± 0.74 years) women participated. Short sleepers slept on average 2 hr less than longer sleepers (297.9 ± 8.2 min versus 418.5 ± 10.9 min) and experienced impaired pain inhibitory response (mean = −21.14 ± 7.9°C versus mean = 15.39 ± 9.5°C; p = 0.005). However, no effect was observed in pain thresholds and pain summation (p > 0.05). Furthermore, pain modulatory responses differed between Mondays and Fridays. Chronic sleep deficiency (< 6 hr) compromises pain responses, notably on Mondays. Maintaining a consistent sleep pattern with sufficient sleep (> 6 hr) throughout the week may protect against pain sensitization and the development of chronic pain in females. Further research is needed, especially in patients with chronic pain. [ABSTRACT FROM AUTHOR]

The aim of this systematic review and meta-analysis was to analyze the accuracy of memory of pain and the variables that may influence it in children with acute, experimental, and chronic pain. We conducted a search in electronic databases from inception to February 11, 2022. Twelve observational studies and 3 randomized controlled studies were included in the study. The main outcome measure was the accuracy of the memory of the pain intensity (experienced/recalled). To compare the outcomes reported by the studies, we calculated the standardized mean difference (SMD) over time for the continuous variables. The overall meta-analysis showed a small effect size in favor of an overestimation of experienced pain intensity (SMD = 0.28). Subanalyzing per pain context, there was a small effect size in favor of overestimation in the clinical context (SMD = 0.33), but there was no evidence of any change in the accuracy of memory of pain in the experimental context (SMD = 0.07). The mean age of the participants and the proportion of girls significantly predicted the accuracy of the memory of pain. The period since the experienced pain measurement, the intensity of expected and recalled fear, trait anxiety, and anxiety sensitivity did not significantly predict the accuracy of the memory of pain. Children showed an overestimation in pain memory between the experienced and recalled intensity of acute pain, especially in a clinical context. Furthermore, only gender and age were predictors of the accuracy of pain memory. These results highlight the relevance of pain memory to medical practice and future research. [ABSTRACT FROM AUTHOR]

IntroductionThis study investigated the variability in lumbar neuromuscular adaptations to pain, the task dependency of pain adaptations and the effect of these adaptations on motor performance.MethodsTwenty-four healthy participants performed isometric back extension contractions at 45° and 90° trunk flexion under pain-free and experimental low back pain conditions induced by electrical stimulation. High-density surface electromyography recorded lumbar muscle activation strategies, and force steadiness was measured using a load cell.ResultsWhile considerable variability in neuromuscular adaptations to lumbar pain was observed among participants, consistent patterns were found between tasks. In the 90° trunk flexion position, both sides exhibited greater magnitudes of pain adaptations for muscle activity redistribution in the mediolateral axis (p

Previous studies have suggested that experimental pain sensitivity is associated with cognitive function. The aim of this study is to assess this relationship in a large population-based sample.

Nociception related salivary biomolecules can be useful patients who are not able to self-report pain. We present the existing evidence on this topic using the PRISMA-ScR guidelines and a more focused analysis of cortisol change after cold pain induction using the direction of effect analysis combined with risk of bias analysis using ROBINS-I. Five data bases were searched systematically for articles on adults with acute pain secondary to disease, injury, or experimentally induced pain. Forty three articles met the inclusion criteria for the general review and 11 of these were included in the cortisol-cold pain analysis. Salivary melatonin, kallikreins, pro-inflammatory cytokines, soluable TNF-α receptor II, secretory IgA, testosterone, salivary α-amylase (sAA) and, most commonly, cortisol have been studied in relation to acute pain. There is greatest information about cortisol and sAA which both rise after cold pain when compared with other modalities. Where participants have been subjected to both pain and stress, stress is consistently a more reliable predictor of salivary biomarker change than pain. There remain considerable challenges in identifying biomarkers that can be used in clinical practice to guide the measurement of nociception and treatment of pain. Standardization of methodology and researchers' greater awareness of the factors that affect salivary biomolecule concentrations are needed to improve our understanding of this field towards creating a clinically relevant body of evidence. [ABSTRACT FROM AUTHOR]

Whether people think less abstractly when they experience physical pain has been examined in previous research. However, the reverse causal possibility—that abstraction reduces sensitivity to painful stimuli—does not appear to have been empirically tested. The aim of this study was to investigate whether abstraction reduces sensitivity to painful stimuli. Using the cold pressor method, university students (N = 205) were exposed to experimental pain. Participants were randomly assigned to an abstract mindset, concrete mindset, cognitive distraction (control task), or no task (control) condition. As a manipulation of abstraction, participants focused on why they felt pain (abstract condition) versus how they felt pain (concrete condition). Pain endurance and pain intensity were evaluated. The abstract mindset condition did not show significantly lower pain sensitivity compared with the other experimental conditions. We found no evidence suggesting that abstract thinking would reduce pain sensitivity. The effectiveness of other techniques that induce abstraction, such as third-person (versus first-person) self-talk should be examined in future research. Since experimentally induced pain in healthy participants differs from clinical pain, whether abstract thinking may reduce pain sensitivity in chronic pain patients should also be examined. [ABSTRACT FROM AUTHOR]

Researchers typically assume that all forms of positive affect (PA) are equally beneficial for attenuating the physiological stress response. We tested whether this association is more nuanced by examining the role of arousal level of PA on physiological responses to acute pain. Participants (N = 283, 75.6% female, Mage = 20.6) were randomized to a low, mid, or high arousal (calm, happy, and excited, respectively) induction condition or to a neutral control and then completed an acute pain-inducing cold pressor task. Sympathetic and parasympathetic responses along with self-reported pain and distress were assessed. Results indicated that the calm condition had a flatter sympathetic reactivity and subsequent recovery compared with the control condition. Additionally, calm and excited were associated with steeper increases in parasympathetic reactivity versus controls. These results support past PA stress buffering findings and indicate that not all types of PA are equal when it comes to improving the pain stress response. Abbreviations: PA: positive affect; PEP: pre-ejection period; RMSSD: root mean square of successive differences.

Pain catastrophizing in the aging population has not been studied in great detail. Existing investigations have reported conflicting results on the effects of age on pain catastrophizing in relation to pain responses. This study investigated the relationship between pain catastrophizing, and its individual components (rumination, magnification, and helplessness), and the responses to standardized experimental pain stimuli in old and young, healthy adults.

Introduction: Distraction is commonly used to reduce pain, but the effectiveness of distractions remains inconclusive. Studies have shown that pain catastrophizing could modulate the effectiveness of distraction strategies. The present study aimed to compare various distraction tasks, then control for pain catastrophizing, and examine how this relationship varies with pain intensity and unpleasantness across different distraction tasks. Methods: Forty-one pain-free participants (aged 27.00 ± 5.41) were recruited for a cross-sectional study. Four types of distraction (cognitive, sensory, emotional, and social) were presented, while moderate pain intensity was induced by electrical stimulation. Before starting the experiment, moderate pain intensity was individually calibrated as six on the Numerical Pain Rating Scale (NRS) to control individual differences in pain sensitivity. Each participant performed all four distraction tasks in a random order. NRS measured pain assessment. Pain catastrophizing was measured by the Pain Catastrophizing Scale (PCS). A repeated measure ANCOVA was conducted to examine the effects of pain dimensions during distraction tasks as a within-subject and pain catastrophizing as a covariate factor. Results: A significant difference was observed in the pain intensity and unpleasantness during cognitive distraction. After controlling for PCS, there were diverse associations between PCS and pain intensity across distinct distraction tasks: social vs. sensory, and cognitive vs. sensory distraction. A consistent pattern in pain unpleasantness emerged with minor variations. This interaction underscored notable distinctions between social vs. sensory and emotional distractions, as well as between cognitive vs. sensory and emotional distractions. However, only the correlation in social distraction remained significant in both pain dimensions. Discussion: Our findings reveal that the link between PCS and pain dimensions varies across different distraction tasks, suggesting diverse interactions. Particularly, social distraction, characterized by both emotional and cognitive states, proves beneficial with lower PCS scores; however, this advantage diminishes as PCS scores increase. [ABSTRACT FROM AUTHOR]

Background and objectives: Some patients with chronic knee pain experience an increase in knee pain following a single bout of exercise involving their knee joint, which can negatively affect exercise adherence and thus result in reduced overall health and lack of disease management. We want to determine whether a single bout of upper-body (UB) aerobic arm-ergometry exercise is effective in reducing the experience of pain in those with chronic knee pain compared with lower-body (LB) aerobic leg ergometry exercise. Methods: A total of 19 individuals (women = 11, men = 8; age = 63 ± 8 years; body mass index = 24 ± 3 kg/m²) who suffered from chronic knee pain for =3 months took part in this study. Arm-ergometry and cycle-ergometry exercises were performed for 30 min at a moderate intensity, separated by 7 days. Pain intensity was assessed by means of a visual analogue scale (VAS) pre- and post-exercise and for 7 days post-exercise. Pressure pain threshold (PPT) and mechanical detection threshold (MDT) were measured pre- and post-exercise at both local and distal anatomical sites. Data are presented as mean ± SD. Results: VAS pain was significantly reduced (p = 0.035) at 1 day post-exercise following the UB exercise trial (-1.4 ± 0.8) when compared with the LB exercise trial (+0.1 ± 2.1). Both UB and LB exercises were effective in reducing local and distal PPT. MDT responses were heterogeneous, and no differences between the UB and LB exercise conditions were noted. Conclusion: An acute bout of upper-body aerobic arm-ergometry exercise evoked a significant decrease in the affected knee joint pain in individuals with chronic knee pain of up to 24 h/1 day post-exercise compared with lower-body aerobic exercise. While the exact mechanisms remain unclear, upper-body exercise may offer a viable, novel therapeutic treatment for patients with chronic knee pain. [ABSTRACT FROM AUTHOR]

IntroductionDistraction is commonly used to reduce pain, but the effectiveness of distractions remains inconclusive. Studies have shown that pain catastrophizing could modulate the effectiveness of distraction strategies. The present study aimed to compare various distraction tasks, then control for pain catastrophizing, and examine how this relationship varies with pain intensity and unpleasantness across different distraction tasks.MethodsForty-one pain-free participants (aged 27.00 ± 5.41) were recruited for a cross-sectional study. Four types of distraction (cognitive, sensory, emotional, and social) were presented, while moderate pain intensity was induced by electrical stimulation. Before starting the experiment, moderate pain intensity was individually calibrated as six on the Numerical Pain Rating Scale (NRS) to control individual differences in pain sensitivity. Each participant performed all four distraction tasks in a random order. NRS measured pain assessment. Pain catastrophizing was measured by the Pain Catastrophizing Scale (PCS). A repeated measure ANCOVA was conducted to examine the effects of pain dimensions during distraction tasks as a within-subject and pain catastrophizing as a covariate factor.ResultsA significant difference was observed in the pain intensity and unpleasantness during cognitive distraction. After controlling for PCS, there were diverse associations between PCS and pain intensity across distinct distraction tasks: social vs. sensory, and cognitive vs. sensory distraction. A consistent pattern in pain unpleasantness emerged with minor variations. This interaction underscored notable distinctions between social vs. sensory and emotional distractions, as well as between cognitive vs. sensory and emotional distractions. However, only the correlation in social distraction remained significant in both pain dimensions.DiscussionOur findings reveal that the link between PCS and pain dimensions varies across different distraction tasks, suggesting diverse interactions. Particularly, social distraction, characterized by both emotional and cognitive states, proves beneficial with lower PCS scores; however, this advantage diminishes as PCS scores increase.

Background and objectivesSome patients with chronic knee pain experience an increase in knee pain following a single bout of exercise involving their knee joint, which can negatively affect exercise adherence and thus result in reduced overall health and lack of disease management. We want to determine whether a single bout of upper-body (UB) aerobic arm-ergometry exercise is effective in reducing the experience of pain in those with chronic knee pain compared with lower-body (LB) aerobic leg ergometry exercise.MethodsA total of 19 individuals (women = 11, men = 8; age = 63 ± 8 years; body mass index = 24 ± 3 kg/m2) who suffered from chronic knee pain for ≥3 months took part in this study. Arm-ergometry and cycle-ergometry exercises were performed for 30 min at a moderate intensity, separated by 7 days. Pain intensity was assessed by means of a visual analogue scale (VAS) pre- and post-exercise and for 7 days post-exercise. Pressure pain threshold (PPT) and mechanical detection threshold (MDT) were measured pre- and post-exercise at both local and distal anatomical sites. Data are presented as mean ± SD.ResultsVAS pain was significantly reduced (p = 0.035) at 1 day post-exercise following the UB exercise trial (−1.4 ± 0.8) when compared with the LB exercise trial (+0.1 ± 2.1). Both UB and LB exercises were effective in reducing local and distal PPT. MDT responses were heterogeneous, and no differences between the UB and LB exercise conditions were noted.ConclusionAn acute bout of upper-body aerobic arm-ergometry exercise evoked a significant decrease in the affected knee joint pain in individuals with chronic knee pain of up to 24 h/1 day post-exercise compared with lower-body aerobic exercise. While the exact mechanisms remain unclear, upper-body exercise may offer a viable, novel therapeutic treatment for patients with chronic knee pain.

Alexandra Ferreira-Valente,1– 3 Benjamin P Van Dyke,4 Melissa A Day,2,5 Catarina Teotónio do Carmo,1 José Pais-Ribeiro,1 Filipa Pimenta,1 Rui M Costa,1 Mark P Jensen2 1William James Center for Research, Ispa – University Institute, Lisbon, Portugal; 2Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA; 3Research Center for Human Development, Faculty of Education and Psychology, Universidade Católica Portuguesa, Porto, Portugal; 4Department of Psychology, Young Harris College, Young Harris, GA, USA; 5School of Psychology, Faculty of Health & Behavioral Sciences, University of Queensland, Brisbane, AustraliaCorrespondence: Alexandra Ferreira-Valente, Research Center for Human Development, Faculty of Education and Psychology, Universidade Católica Portuguesa, Rua de Diogo Botelho, Porto, 1327 4169-005, Portugal, Tel +351 226196200, Email mafvalente@gmail.comPurpose: Previous research supports the usefulness of hypnosis (HYP), mindfulness meditation (MM), and prayer as pain self-management strategies in adults with chronic pain. However, their effects on acute pain have been less researched, and no previous head-to-head study compared the immediate effects of these three approaches on pain-related outcomes. This study compared the immediate effects of HYP, MM, and Christian prayer (CP) on pain intensity, pain tolerance, and stress as assessed by heart rate variability (HRV).Participants and Methods: A total of 232 healthy adults were randomly assigned to, and completed, a single 20-minute session of MM, SH, CP, or an attention control (CN), and underwent two cycles (one pre- and one post-intervention) of Cold Pressor Arm Wrap (CPAW). Sessions were audio-delivered. Participants responded to pre- and post-intervention pain intensity measurements. Pain tolerance (sec) was assessed during the CPAW cycles. HRV was assessed at baseline, and at pre- and post-intervention CPAW cycles. The study protocol was pre-registered at the ClinicalTrials.gov registry (NCT04491630).Results: Small within-group decreases in pain intensity and small increases in pain tolerance were found for HYP and MM from the pre- to the post-intervention. Small within-group improvements in the LH/HF ratio were also found for HYP. The exploratory between-group pairwise comparisons revealed a medium effect size effects of HYP on pain tolerance relative to the control condition. The effects of CP were positive, but small and not statistically significant. Only small to medium, though non-significant, Time × Group interaction effects were found.Conclusion: Study results suggest that single short-term HYP and MM sessions, but not biblical-based CP, may be useful for acute pain self-management, with HYP being the slightly superior option. Future research should compare the effects of different types of prayer and examine the predictors and moderators of these pain approaches’ effects on pain-related outcomes.Keywords: hypnosis, mindfulness meditation, prayer, experimental pain, cold pressor arm wrap

Transcranial magnetic stimulation (TMS) has been used to examine inhibitory and facilitatory circuits during experimental pain and in chronic pain populations. However, current applications of TMS to pain have been restricted to measurements of motor evoked potentials (MEPs) from peripheral muscles. Here, TMS was combined with electroencephalography (EEG) to determine whether experimental pain could induce alterations in cortical inhibitory/facilitatory activity observed in TMS-evoked potentials (TEPs). In Experiment 1 (n=29), multiple sustained thermal stimuli were administered to the forearm, with the first, second, and third block of thermal stimuli consisting of warm but non-painful (pre-pain block), painful (pain block) and warm but non-painful (post-pain block) temperatures, respectively. During each stimulus, TMS pulses were delivered while EEG (64 channels) was simultaneously recorded. Verbal pain ratings were collected between TMS pulses. Relative to pre-pain warm stimuli, painful stimuli led to an increase in the amplitude of the frontocentral negative peak ~45 ms post-TMS (N45), with a larger increase associated with higher pain ratings. Experiments 2 and 3 (n=10 in each) showed that the increase in the N45 in response to pain was not due to changes in sensory potentials associated with TMS, or a result of stronger reafferent muscle feedback during pain. This is the first study to use combined TMS-EEG to examine alterations in cortical excitability in response to pain. These results suggest that the N45 TEP peak, which indexes GABAergic neurotransmission, is implicated in pain perception and is a potential marker of individual differences in pain sensitivity.

The opioid crisis remains a major public health concern, causing significant morbidity and mortality worldwide. Pain is frequently observed among individuals with opioid use disorder (OUD), and the current opioid agonist therapies (OAT) have limited efficacy in addressing the pain needs of this population. We reviewed the most promising non-opioid analgesic therapies for opioid-dependent individuals synthesising data from randomised controlled trials in the Medline database from December 2022 to March 2023. Ketamine, gabapentin, serotoninergic antidepressants, and GABAergic drugs were found to be the most extensively studied non-opioid analgesics with positive results. Additionally, we explored the potential of cannabinoids, glial activation inhibitors, psychedelics, cholecystokinin antagonists, alpha-2 adrenergic agonists, and cholinergic drugs. Methodological improvements are required to advance the development of novel analgesic strategies and establish their safety profile for opioid-dependent populations. We highlight the need for greater integration of experimental pain methods and abuse liability assessments, more granular assessments of prior opioid exposure, greater uniformity of pain types within study samples, and a particular focus on individuals with OUD receiving OAT. Finally, future research should investigate pharmacokinetic interactions between OAT and various non-opioid analgesics and perform reverse translation basic experiments, particularly with methadone and buprenorphine, which remain the standard OUD treatment. [ABSTRACT FROM AUTHOR]

As pain is processed by an extensive network of brain regions, the structural status of the brain may affect pain perception. We aimed to study the association between gray matter volume (GMV) and pain sensitivity in a general population. We used data from 1522 participants in the seventh wave of the Tromsø study, who had completed the cold pressor test (3°C, maximum time 120 seconds), undergone magnetic resonance imaging (MRI) of the brain, and had complete information on covariates. Cox proportional hazards regression models were fitted with time to hand withdrawal from cold exposure as outcome. Gray matter volume was the independent variable, and analyses were adjusted for intracranial volume, age, sex, education level, and cardiovascular risk factors. Additional adjustment was made for chronic pain and depression in subsamples with available information on the respective item. FreeSurfer was used to estimate vertexwise cortical and subcortical gray matter volumes from the T1-weighted MR image. Post hoc analyses were performed on cortical and subcortical volume estimates. Standardized total GMV was associated with risk of hand withdrawal (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.71-0.93). The effect remained significant after additional adjustment for chronic pain (HR 0.84, 95% CI 0.72-0.97) or depression (HR 0.82, 95% CI 0.71-0.94). In post hoc analyses, positive associations between standardized GMV and pain tolerance were seen in most brain regions, with larger effect sizes in regions previously shown to be associated with pain. In conclusion, our findings indicate that larger GMV is associated with longer pain tolerance in the general population. [ABSTRACT FROM AUTHOR]

Introduction: Excessiv generalization of fear contributes to the development and maintenance of pain. Prior research has demonstrated the importance of perception in fear generalization and found that individuals in painful conditions exhibited perceptual bias. However, the extent to which perceptual bias in pain affects the generalization of pain‐related fear and its underlying neural activity remains unclear. Methods: Here, we tested whether perceptual bias in experimental pain individuals led to the overgeneralization of pain‐related fear by recording behavioral and neural responses. To this end, we established an experimental pain model by spraying capsaicin on the surface of the seventh cervical vertebra of the participant. A total of 23 experimental pain participants and 23 matched nonpain controls learned fear conditioning and then completed the fear generalization paradigm combined with the perceptual categorization task. Results: We found that the novel and safety cues were more likely to be identified as threat cues in the experimental group, resulting in higher US expectancy ratings compared to the control group. The event‐related potential results showed that the experimental group exhibited earlier N1 latency and smaller P1 and late positive potential amplitudes than those in the control group. Conclusion: Our findings suggest that the experimental pain individuals exhibited an excessive generalization of fear affected by perceptual bias and reduced their attentional allocation to pain‐related fear stimuli. [ABSTRACT FROM AUTHOR]

Exercise-induced hypoalgesia (EIH) is characterized by an increase in pain threshold following acute exercise. EIH is reduced in some individuals with chronic musculoskeletal pain, although the mechanisms are unknown. It has been hypothesized that this may relate to whether exercises are performed in painful or non-painful body regions. The primary aim of this randomized experimental crossover study was to investigate whether the presence of pain per se in the exercising muscles reduced the local EIH response. The secondary aim was to investigate if EIH responses were also reduced in non-exercising remote muscles. Pain-free women (n=34) participated in three separate sessions. In session 1, the maximal voluntary contraction (MVC) for a single legged isometric knee extension exercise was determined. In sessions 2 and 3, pressure pain thresholds (PPT) were assessed at the thigh and shoulder muscles before and after a 3-min exercise at 30 % of MVC. Exercises were performed with or without thigh muscle pain, which was induced by either a painful injection (hypertonic saline, 5.8 %) or a non-painful injection (isotonic saline, 0.9 %) into the thigh muscle. Muscle pain intensity was assessed with an 11-point numerical rating scale (NRS) at baseline, after injections, during and after exercises. PPTs increased at thigh and shoulder muscles after exercise with painful (14.0–24.9 %) and non-painful (14.3–19.5 %) injections and no significant between-injection EIH differences were observed (p>0.30). Muscle pain intensity was significantly higher following the painful injection compared to the non-painful injection (p<0.001). Exercising painful muscles did not reduce the local or remote hypoalgesic responses, suggesting that the pain-relieving effects of isometric exercises are not reduced by exercising painful body regions. S-20210184. NCT05299268. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Pain experimentally induced in the lumbar region results in task-dependent adaptation of muscle activity and in a reduction of lumbar range of motion. Experimental pain models are frequently used to understand the influence of pain on the control of human movement. In this systematic review, we assessed the effects of experimentally induced pain in the lumbar region of healthy individuals on trunk muscle activity and spine kinematics. Databases were searched from inception up to January 31, 2022. In total, 26 studies using either hypertonic saline injection (n = 19), heat thermal stimulation (n = 3), nociceptive electrical stimulation (n = 3), or capsaicin (n = 1) were included. The identified adaptations were task dependent, and their heterogeneity was partially explained by the experimental pain model adopted. Meta-analyses revealed an increase of erector spinae activity (standardized mean difference = 0.71, 95% confidence interval [CI] = 0.22-1.19) during full trunk flexion and delayed onset of transversus abdominis to postural perturbation tasks (mean difference = 25.2 ms, 95% CI = 4.09-46.30) in the presence of pain. Low quality of evidence supported an increase in the activity of the superficial lumbar muscles during locomotion and during voluntary trunk movements during painful conditions. By contrast, activity of erector spinae, deep multifidus, and transversus abdominis was reduced during postural perturbation tasks. Reduced range of motion of the lumbar spine in the presence of pain was supported by low quality of evidence. Given the agreement between our findings and the adaptations observed in clinical populations, the use of experimental pain models may help to better understand the mechanisms underlying motor adaptations to low back pain. [ABSTRACT FROM AUTHOR]

Alisa J Johnson,1,2,&ast; Taylor Buchanan,3,&ast; Chavier Laffitte Nodarse,1,2 Pedro A Valdes Hernandez,1,2 Zhiguang Huo,4 James H Cole,5,6 Thomas W Buford,3 Roger B Fillingim,1,2,7 Yenisel Cruz-Almeida1,2,7 1Pain Research & Intervention Center of Excellence, University of Florida, Gainesville, FL, USA; 2Department of Community Dentistry & Behavioral Science, College of Dentistry, University of Florida, Gainesville, FL, USA; 3Department of Medicine, University of Alabama, Birmingham, AL, USA; 4Department of Biostatistics, College of Public Health & Health Professions College of Medicine, University of Florida, Gainesville, FL, USA; 5Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK; 6Dementia Research Centre, Institute of Neurology, University College London, London, UK; 7Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA&ast;These authors contributed equally to this workCorrespondence: Yenisel Cruz-Almeida, University of Florida, PO Box 103628, 1329 SW 16th Street, Ste 5180, Gainesville, FL, 32608, USA, Tel +1 352-294-8584, Fax +1 352-273-5985, Email cryeni@ufl.eduPurpose: Knee OA-related pain varies in impact across individuals and may relate to central nervous system alterations like accelerated brain aging processes. We previously reported that older adults with chronic musculoskeletal pain had a significantly greater brain-predicted age, compared to pain-free controls, indicating an “older” appearing brain. Yet this association is not well understood. This cross-sectional study examines brain-predicted age differences associated with chronic knee osteoarthritis pain, in a larger, more demographically diverse sample with consideration for pain’s impact.Patients and Methods: Participants (mean age = 57.8 ± 8.0 years) with/without knee OA-related pain were classified according to pain’s impact on daily function (ie, impact): low-impact (n=111), and high-impact (n=60) pain, and pain-free controls (n=31). Participants completed demographic, pain, and psychosocial assessments, and T1-weighted magnetic resonance imaging. Brain-predicted age difference (brain-PAD) was compared across groups using analysis of covariance. Partial correlations examined associations of brain-PAD with pain and psychosocial variables.Results: Individuals with high-impact chronic knee pain had significantly “older” brains for their age compared to individuals with low-impact knee pain (p < 0.05). Brain-PAD was also significantly associated with clinical pain, negative affect, passive coping, and pain catastrophizing (p’s< 0.05).Conclusion: Our findings suggest that high impact chronic knee pain is associated with an older appearing brain on MRI. Future studies are needed to determine the impact of pain-related interference and pain management on somatosensory processing and brain aging biomarkers for high-risk populations and effective intervention strategies.Keywords: knee osteoarthritis, high impact chronic pain, brain aging, experimental pain, psychosocial

The current study examined youths' and their parents' perceptions concerning participation in an investigation of spontaneous and induced pain during recovery from laparoscopic appendectomy. Youth (age range 5-17 years) and their parents independently completed surveys about their study participation. On a 0 (very negative) -to-10 (very positive) scale, both parents 9.4(1.3) [mean(SD)] and youth 7.9(2.4) rated their experience as positive. Among youth, experience ratings did not differ by pain severity and survey responses did not differ by age. Most youth (83%) reported they would tell another youth to participate. Ethical issues regarding instigation of pain in youth for research purposes are examined.

Abstract Background Healthy subjects showed normal variance of cervical spine reposition errors of approximately 2 degrees. Effects of experimental pain on cervical spine reposition errors were unknown; thus, the purpose of this study was to investigate the effects of experimental pain on cervical spine reposition errors. Methods A repeated measured study design was applied. Thirty healthy subjects (12 males) were recruited. Reposition errors were extracted from upright cervical positions before and after cervical flexion movement in healthy subjects before and during experimental neck pain. Cervical spine reposition errors were calculated based on anatomical landmarks of each cervical joint. Reposition errors were extracted in degrees as constant errors and absolute errors for further statistical analysis. Repeated measures analysis of variance (RM-ANOVA) was applied to analyse experimental pain effects on either constant errors or absolute errors of different cervical joints. Results The cervical spine showed non-significant difference in reposition errors regarding the constant errors (P>0.05) while larger reposition errors regarding the absolute errors during experimental pain compared to before experimental pain (P

Background. Alterations in pain perception have been observed in people diagnosed with schizophrenia. Some research suggests the existence of a possible hyposensitivity, while others describe a hypersensitivity to pain in people with schizophrenia. In summary, the studies present contradictory results. Methods. A systematic review of experimental and comparative studies has been conducted in 5 different databases, including those studies that measure pain experimentally inducing it with physical methods and that compares the results with a healthy control group. Afterwards, a meta-analysis was carried out comparing the patients with schizophrenia to the healthy controls, using the random effects model. Results. Nine studies were finally selected, with a total of 186 participants diagnosed with schizophrenia and 186 healthy controls. In the meta-analysis, no significative differences were observed in the general analysis. But when the type of stimuli was studied separately (mechanical, thermal, or electrical), significative differences in favor of a higher sensitivity in the patients with schizophrenia were observed in the studies that measured pain with mechanical pressure or ischemia, not in those that used thermal or electrical methods. Conclusions. The global result of our systematic review does not support the existence of an alteration in pain sensitivity in subjects with schizophrenia, although a subgroup analysis suggests that when pain stimulation is caused by mechanical methods, people with schizophrenia present hypersensitivity to pain compared to healthy controls. Although these results are novel data, more studies are required to replicate these results. [ABSTRACT FROM AUTHOR]

Objectives: Peripheral neuropathies that occur secondary to nerve injuries may be painful or painless, and including a low-grade inflammation and pro-inflammatory cytokines associated with both regeneration and damage of peripheral nerve cells and fibers. Currently, there are no validated methods that can distinguished between neuropathic pain and painless neuropathy. The aim of this study was to search for proinflammatory and anti-inflammatory proteins associated with pain and experimental pain sensitivity in subjects with surgeon-verified nerve injuries in the upper extremities. Methods: One hundred and thirty-one subjects [69 with neuropathic pain, NP; 62 with painless neuropathy, nP] underwent a conditioned pain modulation (CPM) test that included a cold pressor task (CPT) conducted with the non-injured hand submerged in cold water (4 °C) until pain was intolerable. CPM was assessed by pain ratings to pressure stimuli before and after applying the CPT. Efficient CPM effect was defined as the ability of the individual's CS to inhibit at least 29% of pain (eCPM). The subjects were assigned to one of two subgroups: pain sensitive (PS) and pain tolerant (PT) after the time they could tolerate their hand in cold water (PS<40 s and PT=60 s). Plasma samples were analyzed for 92 proteins incorporated in the inflammation panel using multiplex Protein Extension Array Technology (PEA). Differentially expressed proteins were investigated using both univariate and multivariate analysis (principal component analysis-PCA and orthogonal partial least-squares discriminant analysis-OPLS-DA). Results: Significant differences in all protein levels were found between PS and PT subgroups (CV-ANOVA p<0.001), but not between NP and nP groups (p=0.09) or between inefficient CPM (iCPM) and eCPM (p=0.53) subgroups. Several top proteins associated with NP could be detected using multivariate regression analysis such as stromelysin 2 (MMPs), interleukin-2 receptor subunit beta (IL2RB), chemokine (C-X-C motif) ligand 3 (CXCL3), fibroblast growth factor 5 (FGF5), chemokine (C-C motif) ligand 28 (CCL28), CCL25, CCL11, hepatocyte growth factor (HGF), interleukin 4 (IL4), IL13. After adjusting for multiple testing, none of these proteins correlated significantly with pain. Higher levels of CCL20 (p=0.049) and CUB domain-containing protein (CDCP-1; p=0.047) were found to correlate significantly with cold pain sensitivity. CDCP-1 was highly associated with both PS and iCPM (p=0.042). Conclusions: No significant alterations in systemic proteins were found comparing subjects with neuropathic pain and painless neuropathy. An expression of predominant proinflammatory proteins was associated with experimental cold pain sensitivity in both subjects with pain and painless neuropathy. One these proteins, CDC-1 acted as "molecular fingerprint" overlapping both CPM and CPT. This observation might have implications for the study of pain in general and should be addressed in more detail in future experiments. [ABSTRACT FROM AUTHOR]

In this systematic review, we synthesize the literature investigating the effect of experimentally induced pain in the cervical, shoulder, or orofacial regions on cervical neuromuscular and kinematic features. Databases were searched up to November 1, 2023. A total of 29 studies using hypertonic saline injection (n = 27) or glutamate injection (n = 2) as experimental pain models were included. Meta-analyses revealed reduced upper trapezius activation during shoulder flexion/abduction when pain was induced in the upper trapezius (standardized mean difference: -.90, 95% confidence interval: [-1.29; -.51]), splenius capitis (-1.03 [-1.44; -.63]), and supraspinatus (-.63 [-1.25; -.01]), but not in the subacromial space (.22 [-.16; .60]). Furthermore, experimentally induced pain caused a caudal redistribution of activation within the upper trapezius (.96 [.58; 1.34]) but did not change the mediolateral distribution (.11 [-.22; .42]). None of these adaptations persisted after pain resolution. Low-quality evidence supported the absence of an effect of experimental pain on upper trapezius muscle activation during manual dexterity and cervical flexion/extension tasks, as well as on cervical flexor and extensor muscle activation during cervical and jaw tasks. Inconsistent and limited evidence, attributed to the large heterogeneity of task and outcomes, precluded drawing meaningful conclusions about the effects of experimentally induced pain in the cervical region on cervical kinematics. Overall, cervical muscle activation tended to decrease in response to experimentally induced pain, and the decrease of muscle activation depended on the location of the painful stimulus. These adaptations are only partially representative of muscle activation patterns observed in clinical populations. PERSPECTIVE: This systematic review and meta-analysis revealed a reduced or unchanged muscle activation during experimental pain in the cervical, shoulder, or orofacial regions, depending on the task and location of nociceptive stimulation. There was inconsistent evidence on cervical kinematics. These findings enhance our understanding of neuromuscular adaptations to acute experimental pain., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background and purposeWe and others have reported ethnic/race group differences in clinical pain, physical function, and experimental pain sensitivity. However, recent research indicates that with consideration for socioenvironmental factors, ethnicity/race differences become less or non-significant. Understanding of factors contributing to pain inequities are needed. Guided by the NIA and NIMHD Health Disparities Research Frameworks, we evaluate the contributions of environmental and behavioral factors on previously reported ethnic/race group differences in: (1) clinical pain, (2) physical function, and (3) experimental pain in individuals with knee pain.MethodsBaseline data from Understanding of Pain and Limitations in Osteoarthritis Disease (UPLOAD) and UPLOAD-2 studies were analyzed. Participants were adults 45 to 85 years old who self-reported as non-Hispanic white (NHW) or black (NHB) with knee pain. A health assessment and quantitative sensory testing were completed. Sociodemographics, environmental, health, clinical and experimental pain, and physical functioning measures were included in nested regressions.ResultsPooled data from 468 individuals, 57 ± 8 years of age, 63% women, and 53% NHB adults. As NHB adults were younger and reported greater socioenvironmental risk than the NHW adults, the term sociodemographic groups is used. With inclusion of recognized environmental and behavioral variables, sociodemographic groups remained a significant predictor accounting for

A common symptom in neuromuscular diseases is pain, which changes human movement in many ways. Using the decomposed electromyographic signal, we investigate the strategy of the brain in recruiting different pools of motor units (MUs) to produce torque during induced muscle pain in terms of firing rate (FR), recruitment threshold (RT) and action potential amplitude (MUAPAMP). These properties were used to define two groups (G1/G2) based on a K-means clusterization method. A 2.0 mL intramuscular hypertonic (6%) or isotonic (0.9%) saline solution was injected to induce pain or act as a placebo during isometric and isokinetic knee extension contractions. While isometric torque decreases after pain induction with hypertonic solution, this does not occur in isokinetic torque. This occurs because the MUs re-organized after the injection of both solutions. This is supported by an increase in RT, in both G1 and G2 MUs. However, when inducing pain with the hypertonic solution, RT increase is exacerbated. In this condition, FR also decreases, while MUAPAMP increases only for G1 MUs. Therefore, this study proposes that the strategy for maintaining force production during pain is to recruit MUs with higher RT and MUAPAMP. [ABSTRACT FROM AUTHOR]

Several studies suggest that acute pain decreases corticomotor excitability. However, the variability between patients remains important and unexplained. The aim of this study was to unveil potential sources of variation by looking at the effect of kinesiophobia and pain catastrophizing on pain-induced corticomotor modulation. Corticomotor excitability was assessed with the slopes of recruitment curves measured from the first dorsal interosseous elicited by transcranial magnetic stimulation before and during pain induced by capsaicin application on the forearm. Participants completed the Tampa Scale for Kinesiophobia (TSK) and the Pain Catastrophizing Scale (PCS). Twenty-four persons participated in the study. There was a moderate and positive correlation between individual changes in the slope of the recruitment curves and TSK questionnaire scores (r s =0.47; p = 0.02). During the painful condition, unlike those with higher TSK scores, participants with lower TSK scores demonstrated recruitment curves with reduced slopes compared to baseline. There was a difference between changes in the slopes of recruitment curves between individuals with "highest" vs. "lowest" kinesiophobia scores (p = 0.01). No relationship was observed between changes in the slopes of the recruitment curves and PCS scores (p = 0.20). The results suggest that kinesiophobia may affect neuromotor processes and influence the corticomotor pain response. Higher kinesiophobia scores during experimental induced pain were associated with smaller decreases in the slopes of recruitment curves. These findings suggest that there is less inhibition of corticospinal excitability in participants with greater TKS scores. [ABSTRACT FROM AUTHOR]

Objectives: Early memories of pain contribute to fear and may underlie the maintenance and development of chronic pain into adulthood. Accordingly, understanding determinants that may impact children's pain memory development is key. This study examined (a) the effect of a brief engaging pain educational video in healthy children before undergoing an experimental pain task upon children's recalled pain intensity and pain-related fear and (b) the moderating role of parental pain- and non-pain-attending verbalizations before and after the pain task.Methods: Seventy-seven children (8-15 years old) participated in an experimental heat pain task, including actual heat pain stimuli delivered through a thermode on their forearm. Children were randomized to the experimental group (i.e., watching a pain educational video) or the control group (i.e., no video). Children's recalled pain intensity and pain-related fear were elicited 2 weeks later.Results: Findings showed that recalled pain intensity (but not recalled pain-related fear) of children who watched the pain educational video was significantly lower compared to the control group (p = .028). Further, parental pain-attending verbalizations before the pain task moderated the impact of the video upon children's recalled pain intensity (p = .038). Specifically, children in the control group, but not the experimental group, whose parents used less pain-attending verbalizations recalled higher pain intensity, whereas children whose parents used more pain-attending verbalizations recalled lower pain intensity.Conclusions: As children's pain memories have important implications for pain assessment, treatment, and health across the lifespan, these findings might have important implications for the prevention of development or maintenance of maladaptive pain-related outcomes. [ABSTRACT FROM AUTHOR]

We studied whether there exist variations in pain responses between different intellectual and developmental disability (IDD) etiologies. Self-reports and facial expressions (Facial Action Coding System = FACS) were recorded during experimental pressure stimuli and compared among 31 individuals with IDD-13 with cerebral palsy (CP), nine with Down syndrome (DS), nine with unspecified origin (UIDD)-and among 15 typically developing controls (TDCs). The CP and DS groups had higher pain ratings and FACS scores compared to the UIDD and TDC groups, and steeper stimulus-response functions. The DS group exhibited the most diverse facial expressions. There were variations in the foci of facial expressions between groups. It appears that different IDD etiologies display distinct pain responses. [ABSTRACT FROM AUTHOR]

Background : To investigate the analgesic effects of vibro-acupuncture (VA), a novel acuvibrator was developed. Objectives: To compare the analgesic effects of VA with those of manual acupuncture (MA) and placebo acupuncture (PA) on subjects with normal sensory perception (Study I), experimentally induced acute pain (Study II), and clinical chronic pain (Study III). Methods : Thirty healthy volunteers (21 males, age: 20-30 years) participated in Study I. Fourteen healthy volunteers (8 males, age: 20-32 years) participated in Study II in which experimental pain was induced by injection of hypertonic saline. Fourteen patients suffering from unilateral epicondylalgia (9 males, age: 30-61 years) participated in Study III. All participants received VA, MA, and PA at LI4 and LI10 points in a randomized, crossover, and double-blinded manner. Quantitative sensory testing (QST) was performed on the ipsilateral forearm before and after each treatment. Data were analyzed using repeated-measures (RM) ANOVA. Results : A significantly higher vibration detection threshold (VDT) was observed after treatment of VA than after MA and PA (p < 0.001). No significant treatment effect on experimental pain intensity was detected (p > 0.086). Significantly lower pain intensity (p = 0.005) and a smaller drawing area (p = 0.011) of unilateral epicondylalgia were found after VA treatment than after PA. Conclusion : A specific effect on the VDT beyond that of MA and PA was evoked by VA. Patients with epicondylitis showed significantly lower pain intensity during VA than during PA. This study indicated that VA may be beneficial in individuals with clinical chronic musculoskeletal pain; however, further studies are needed.

Abstract: The nociceptive flexion reflex (NFR) is a spinally mediated withdrawal response and is used as an electrophysiological marker of descending modulation of spinal nociception. Chemical and pharmacological modulation of nociceptive neurotransmission at the spinal level has been evidenced by direct effects of neurotransmitters and pharmacological agents on the NFR. Largely unexplored are, however, the effects of nonpharmacological noninvasive conservative interventions on the NFR. Therefore, a systematic review and meta-analysis was performed and reported following the PRISMA guidelines to determine whether and to what extent spinal nociception measured through the assessment of the NFR is modulated by conservative therapy in patients and healthy individuals. Five electronic databases were searched to identify relevant articles. Retrieved articles were screened on eligibility using the predefined inclusion criteria. Risk of bias was investigated according to Version 2 of the Cochrane risk-of-bias assessment tool for randomized trials. The evidence synthesis for this review was conducted in accordance with the Grading of Recommendations Assessment, Development and Evaluation. Thirty-six articles were included. Meta-analyses provided low-quality evidence showing that conservative therapy decreases NFR area and NFR magnitude and moderate-quality evidence for increases in NFR latency. This suggests that conservative interventions can exert immediate central effects by activating descending inhibitory pathways to reduce spinal nociception. Such interventions may help prevent and treat chronic pain characterized by enhanced spinal nociception. Furthermore, given the responsiveness of the NFR to conservative interventions, the NFR assessment seems to be an appropriate tool in empirical evaluations of treatment strategies.PROSPERO registration number: CRD42020164495. [ABSTRACT FROM AUTHOR]

Objectives: Exercise-induced hypoalgesia (EIH) is a decrease in the pain sensitivity after exercise. Individuals with chronic pain show less EIH after one exercise session compared with pain-free individuals possibly due to pain in exercising muscles. The primary aim of this randomized controlled cross-over study was to compare the EIH response at the exercising thigh muscle following exercises performed with painful vs. non-painful muscles. Secondary aims were to explore if a reduced EIH response was confined to the painful muscle, and whether the muscle pain intensity and the EIH responses were negatively associated. Methods: In two sessions, 34 pain-free participants received a painful (hypertonic saline, 5.8%) injection and a control (isotonic saline, 0.9%) injection in the right thigh muscle before performing a 3 min isometric wall squat exercise. Pressure pain thresholds (PPTs) were assessed at both thighs and the left neck/shoulder at baseline, after injections and after exercise. Pain intensities in the thighs were rated on numerical rating scales (NRS: 0-10). Results: Hypertonic saline induced moderate thigh pain at rest (NRS: 4.6 ± 2.1) compared to the control injection (NRS: 0.3 ± 0.4; p<0.001). EIH at the thighs and neck/shoulder were not different between sessions (Injected thigh: 0 kPa; 95% CI: -51 to 52; Contralateral thigh: -6 kPa; 95% CI: -42 to 30; neck/shoulder: 19 kPa; 95% CI: -6 to 44). No significant associations between pain intensity ratings immediately after the Painful injection and EIH responses at any assessment sites were found (right thigh: β=0.08, 95% CI: -12.95 to 20.64, p=0.64, left thigh: β=-0.33, 95% CI: -27.86 to 0.44, p=0.06; neck/shoulder: β=-0.18, 95% CI: -15.11 to 4.96, p=0.31). Conclusions: Pain in the area of an exercising muscle did not reduce local or systemic EIH responses. Trial registration number: NCT04354948. [ABSTRACT FROM AUTHOR]

Background: Healthy subjects showed normal variance of cervical spine reposition errors of approximately 2 degrees. Effects of experimental pain on cervical spine reposition errors were unknown; thus, the purpose of this study was to investigate the effects of experimental pain on cervical spine reposition errors.Methods: A repeated measured study design was applied. Thirty healthy subjects (12 males) were recruited. Reposition errors were extracted from upright cervical positions before and after cervical flexion movement in healthy subjects before and during experimental neck pain. Cervical spine reposition errors were calculated based on anatomical landmarks of each cervical joint. Reposition errors were extracted in degrees as constant errors and absolute errors for further statistical analysis. Repeated measures analysis of variance (RM-ANOVA) was applied to analyse experimental pain effects on either constant errors or absolute errors of different cervical joints.Results: The cervical spine showed non-significant difference in reposition errors regarding the constant errors (P>0.05) while larger reposition errors regarding the absolute errors during experimental pain compared to before experimental pain (P<0.001). In addition, the pain level joint (C4/C5) and its adjacent joints (C3/C4 and C5/C6) indicated larger reposition errors regarding absolute errors (P=0.035, P=0.329 and P=0.103, respectively).Conclusions: This study firstly investigated the cervical spine reposition errors in experimental neck pain and further found the joints adjacent to the pain level showed larger errors compared to the distant joints regarding absolute errors. It may imply that the larger reposition errors in specific cervical joint indicate probable injury or pain existed adjacent to the joints. [ABSTRACT FROM AUTHOR]

Objectives: Pain on palpation of jaw muscles is a commonly used diagnostic criterion when examining patients with orofacial pain. It is not known, however, if pain reports are affected by the gender of the examiner. Our aim was to investigate if pressure pain threshold (PPT), pressure pain tolerance (PTol), and pain intensity assessed over the masseter muscles in healthy individuals are affected by the gender of the examiner. Materials and methods: Healthy, pain-free individuals were recruited on a voluntary basis. PPT and PTol were assessed using pressure algometry. At the PTol level, participants also rated pain intensity on a 0–10 numeric rating scale. Assessments of PPT and PTol were conducted with six repeated measurements performed twice, separately by one female and one male examiner, on each participant. Results: In total, 84 participants (43 women; median age 24, IQR 6) were included. With a female examiner, women reported higher pain intensity than men (Mann Whitney U, p = 0.005). In the multivariable analysis, significantly higher PTol was predicted by male examiner. Also, a higher ratio between PTol and reported pain intensity was predicted by male examiner. Conclusions: The gender of the examiner influences pain reporting and perception in an experimental setting. This effect on pain perception related to gender of the examiner is probably related to normative gender behaviors rather than to biological alterations within the examined individual. Clinical relevance: In clinical and experimental settings, gender of the examiner may affect not only pain perception but also pain reporting, with potential implications for diagnostics in patients with pain. [ABSTRACT FROM AUTHOR]

Abstract Background An increasing number of patients come to the operating room in use of opioid analgesics. They have different levels of tolerance to opioid effects which challenge the anesthesiologists in search of safe and effective opioid dosing perioperatively. The tested hypothesis is that simple measures introduced will allow us to measure tolerance qualitatively. Opioid effects on pain (analgesia) and dyspnea sensations (relieving effect) are tested. Patients were allocated to three groups according to pre-operative analgesics: (1) control, without any opioid analgesics, (2) weak opioid, and (3) strong opioid. Pressure pain threshold (PPT) and no-respiratory sensation period (NRSP) were measured at two points: before and 3 min after intravenous fentanyl administration. Results A total of 58 (43 controls, 9 weak opioids, and 6 strong opioids) patients were enrolled. PPT and NRSP, after iv 2 μg/kg ideal body weight (IBW) fentanyl, were significantly elevated in the control patients (PPT: 6.2 ± 2.1 N to 9.2 ± 3.9 N, p < 0.0001, NRSP: 17.8 ± 10.8 s to 22.8 ± 18.7 s, p < 0.005, paired t test). However, preoperative opioid use, though with tendency, did not show a significant decrease of the opioid effect. Due to an insufficient number of participants, no conclusion could be drawn. Further analysis of the data from control patients showed a significant difference between the two sexes in sensitivity to PPT and NRSP, as well as fentanyl effect on PPT. Conclusions Current data showed a simple method of measuring the opioid effect on two dimensions: pain and respiration. Though not able to show a qualitative measurement of tolerance formation in opioid-users, data from control patients showed females to be more sensitive to pain and dyspnea but is less sensitive to the opioid effect. Further studies are necessary to show whether these gender differences serve as clinical relevance. Trial registration UMIN, UMIN 000011580. Registered 27 August 2013, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000013352&language=J

Ines Daguet,1,2 Kayla Bergeron-Vezina,1,2 Marie-Philippe Harvey,1,2 Marylie Martel,1,2 Alexia Coulombe-Leveque,1– 3 Guillaume Leonard1– 3 1Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; 2Research Centre on Aging, CIUSSS de l’Estrie - CHUS, Sherbrooke, QC, Canada; 3School of Rehabilitation, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, CanadaCorrespondence: Guillaume LeonardResearch Centre on Aging, CIUSSS de l’Estrie – CHUS, 1036, rue Belvédère Sud, Sherbrooke, Québec J1H 4C4, CanadaTel +1 819-780-2220 Ext 45246Fax +1 819-820-6864Email guillaume.leonard2@usherbrooke.caBackground and Purpose: Aging is associated with an impairment of diverse physiological functions, including nociception. For example, older adults in comparison to young adults, show an overall increase in pain thresholds, reflecting a decline in pain sensitivity and changes in the nociceptive pathways. These results are, however, debated as they were not always replicated depending on the stimulus modality, duration, and location. The aim of the current study was to determine how the temporal evolution of pain intensity during a continuous tonic heat pain test is influenced by aging. More specifically, we wanted to 1) assess the effect of age on initial peak and late-phase pain and 2) determine whether potential age effects depend on the stimulation site.Participants and Methods: 13 young adults (average of 27.9 years old) and 13 older adults (average of 67.5 years old) participated in this study. Experimental heat pain was evoked on an appendicular (forearm) and axial (lower-back) body region, using a thermode (2-minute stimulation at a constant, individually-adjusted temperature). During the nociceptive stimulation, participants used a computerized visual analogue scale to continuously rate their pain.Results: We show that initial peak (0– 30 seconds) pain sensation was significantly lower in older adults compared to young adults, while late-phase (30– 120 seconds) pain sensation was similar across the two age groups. These results hold true for both stimulation sites, suggesting the existence of an age effect on both appendicular and axial body regions.Conclusion: The lower magnitude of initial peak pain observed in older adults, which affects both appendicular and axial body regions, could reflect generalized peripheral or central alterations of the nociceptive system in older adults. These alterations in older adults could have significant clinical impacts, such as an increased vulnerability to injury or an underestimation of the severity of their pain condition.Keywords: pain, experimental pain, age, aging, elderly, psychophysics