Widespread Proprioceptive Acuity Impairment in Chronic Back Pain: A Cross-sectional Study.

OBJECTIVE: To investigate whether proprioceptive accuracy measured with the Joint Position Sense (JPS) in patients with chronic neck and low back pain is impaired exclusively in affected areas or also in distant areas, not affected by pain. DESIGN: Cross-sectional study. SETTING: Interdisciplinary outpatient rehabilitation clinic for back and neck pain. PARTICIPANTS: Patients with chronic neck pain (n=30), patients with chronic low back pain (n=30), and age- and sex-matched asymptomatic control subjects (n=30; N=90). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients and asymptomatic control subjects completed a test procedure for the JPS of the cervical spine, lumbar spine, and ankle in a randomized order. Between group differences were analyzed with the univariate analysis of variance and associations of the JPS with clinical features using the Pearson's correlation coefficient. RESULTS: Both patients with chronic neck pain (P<.001) and patients with chronic low back pain (P<.01) differed significantly from asymptomatic controls in the JPS of the cervical spine, lumbar spine and ankle joint, regardless of the painful area. No difference was shown between patient groups (P>.05). An association of the JPS with clinical characteristics, however, could not be shown. CONCLUSION: These results suggest widespread impairment of proprioceptive accuracy in patients with chronic and low back pain and a role for central sensorimotor processes in musculoskeletal pain conditions.

Objective Measurement of Subjective Pain Perception with Autonomic Body Reactions in Healthy Subjects and Chronic Back Pain Patients: An Experimental Heat Pain Study.

Multiple attempts to quantify pain objectively using single measures of physiological body responses have been performed in the past, but the variability across participants reduces the usefulness of such methods. Therefore, this study aims to evaluate whether combining multiple autonomic parameters is more appropriate to quantify the perceived pain intensity of healthy subjects (HSs) and chronic back pain patients (CBPPs) during experimental heat pain stimulation. HS and CBPP received different heat pain stimuli adjusted for individual pain tolerance via a CE-certified thermode. Different sensors measured physiological responses. Machine learning models were trained to evaluate performance in distinguishing pain levels and identify key sensors and features for the classification task. The results show that distinguishing between no and severe pain is significantly easier than discriminating lower pain levels. Electrodermal activity is the best marker for distinguishing between low and high pain levels. However, recursive feature elimination showed that an optimal subset of features for all modalities includes characteristics retrieved from several modalities. Moreover, the study's findings indicate that differences in physiological responses to pain in HS and CBPP remain small.

Explainable Artificial Intelligence (XAI) in Pain Research: Understanding the Role of Electrodermal Activity for Automated Pain Recognition.

Artificial intelligence and especially deep learning methods have achieved outstanding results for various applications in the past few years. Pain recognition is one of them, as various models have been proposed to replace the previous gold standard with an automated and objective assessment. While the accuracy of such models could be increased incrementally, the understandability and transparency of these systems have not been the main focus of the research community thus far. Thus, in this work, several outcomes and insights of explainable artificial intelligence applied to the electrodermal activity sensor data of the PainMonit and BioVid Heat Pain Database are presented. For this purpose, the importance of hand-crafted features is evaluated using recursive feature elimination based on impurity scores in Random Forest (RF) models. Additionally, Gradient-weighted class activation mapping is applied to highlight the most impactful features learned by deep learning models. Our studies highlight the following insights: (1) Very simple hand-crafted features can yield comparative performances to deep learning models for pain recognition, especially when properly selected with recursive feature elimination. Thus, the use of complex neural networks should be questioned in pain recognition, especially considering their computational costs; and (2) both traditional feature engineering and deep feature learning approaches rely on simple characteristics of the input time-series data to make their decision in the context of automated pain recognition.

Psychophysical testing in chronic migraine and chronic tension type headache: An observational study.

BACKGROUND: Clinical presentation is the key to the diagnosis of patients with migraine and tension-type headache, but features may overlap when both become chronic. Psychophysical parameters may distinguish both conditions. We aimed to compare psychophysical aspects of patients with chronic migraine, chronic tension-type headache and headache-free controls, and to determine whether these can predict headache frequency. METHODS: An examiner blinded to the diagnosis assessed 100 participants (chronic migraine (n = 38), chronic tension-type headache (n = 31) and controls (n = 31)). Assessed variables included painful area, pressure pain thresholds, temporal summation, cervical range of motion, neck posture, headache and neck impact, quality of life, and kinesiophobia. Comparison between groups was performed with one-way ANOVA and multiple linear regression was used to assess the headache frequency predictors. RESULTS: We found differences of both headache groups compared to controls (p < 0.01), but not between headache groups. Neck disability was a significant predictor of headache frequency for chronic tension-type headache (adjusted R2 = 0.14; ß = 0.43; p = 0.03) and chronic migraine (adjusted R2 = 0.18; ß = 0.51; p < 0.01). CONCLUSIONS: Chronic tension-type headache and chronic migraine showed similar psychophysical results, but were significantly worse when compared to controls. The psychophysical examination did not discriminate between headache types. The variable best explaining headache frequency for both headache types was neck disability.

Postural control impairment in patients with headaches-A systematic review and meta-analysis.

OBJECTIVE: To summarize the evidence regarding static and dynamic balance alterations among patients with headache. METHODS: Electronic databases (PubMed, CINAHL, and Web of Science) were searched by two researchers independently up to September 2021. Two reviewers selected eligible studies, extracted the data, and assessed the quality of evidence using the Downs and Black checklist. Case-control studies were included if they involved balance assessment of any kind of headache, including objective outcome measures of dynamic and static tests such as body sway displacement, limits of stability (LOS), gait, and tandem walk tests. A meta-analysis and post hoc sensitivity analyses were performed when possible. RESULTS: Twenty-two studies (1202 patients with headache and 597 controls) were included in this review and 16 of them in the meta-analysis. Risk of bias ranged from low to moderate among all studies. Greater sway area in static posturography was shown by patients with migraine in comparison to controls, with more consistent differences in more challenging test conditions, such as over a foam surface with eyes closed (difference of 4.8 cm2 , 95% CI: 3.8-5.9). Lower performance of patients with migraine during the tandem walk test (difference of -7.8 cm/s, 95% CI: -9.0 to -6.5) and slower reaction time in the LOS test (difference of 0.3 s, 95% CI: 0.2-0.4) were also verified. There is no evidence of altered sway velocity and length in static posturography among patients with migraine (p > 0.05). The level of evidence is very low for balance alteration of any kind among patients with tension-type and cervicogenic headache owing to the limited number of studies and high heterogeneity. CONCLUSION: This review confirmed the presence of static and dynamic balance alterations among patients with migraine. Future studies with low risk of bias are needed to decrease heterogeneity in methodology and explore the role of subdiagnosis on the balance of patients with headache.

Offset analgesia is increased intra-orally.

BACKGROUND: Offset analgesia (OA) is commonly used to quantify endogenous pain inhibition. However, the potential role of afferent inputs and the subsequent peripheral factors from different body areas on the underlying mechanisms are still unclear. OBJECTIVES: The aim of this cross-sectional study was to compare the magnitude of OA in four different body areas representing (a) glabrous and non-glabrous skin, (b) trigeminal and extra-trigeminal areas, and (c) intra- and extra-oral tissue. METHODS: OA was assessed at the oral mucosa of the lower lip, the skin of the cheek, the forearm and the palm of the hand in 32 healthy and pain-free participants. OA testing included two trials: (1) a constant trial (30 s of constant heat stimulation at an individualised temperature of Pain50 [pain intensity of 50 out of 100]) and (2) an offset trial (10 s of individualised Pain50 , followed by 5 s at Pain50 + 1°C and 15 s at Pain50 ). Participants continuously rated their pain during each trial with a computerised visual analogue scale. RESULTS: A significant OA response was recorded at the oral mucosa (p < .001, d = 1.24), the cheek (p < .001, d = 0.84) and the forearm (p < .001, d = 1.04), but not at the palm (p = .19, d = 0.24). Significant differences were shown for OA recorded at the cheek versus the mucosa (p = .02), and between palm and mucosa (p = .007), but not between the remaining areas (p > .05). CONCLUSION: This study suggests that intra-oral endogenous pain inhibition assessed with OA is enhanced and supports the role of peripheral mechanisms contributing to the OA response.

Investigation of Correlations Between Pain Modulation Paradigms.

OBJECTIVE: Endogenous pain modulation can be quantified through the use of various paradigms. Commonly used paradigms include conditioned pain modulation (CPM), offset analgesia (OA), spatial summation of pain (SSP), and temporal summation of pain (TSP), which reflect spatial and temporal aspects of pro- and antinociceptive processing. Although these paradigms are regularly used and are of high clinical relevance, the underlying physiological mechanisms are not fully understood. DESIGN: The aim of this study is therefore to assess the association between these paradigms by using comparable protocols and methodological approaches. SETTING: University campus. SUBJECTS: Healthy and pain-free volunteers (n = 48) underwent psychophysical assessment of CPM, OA, SSP, and TSP (random order) at the same body area (volar nondominant forearm) with individualized noxious stimuli. METHODS: CPM included heat stimuli before, during, and after a noxious cold-water bath, whereas for OA, three heat stimuli were applied: baseline trial, offset trial, and constant trial. For the SSP paradigm, two differently sized heat stimulation areas were evaluated, whereas for TSP, the first and last stimulus of 10 consecutive short heat stimuli were assessed. A computerized visual analog scale was used to continuously evaluate pain intensity. The magnitudes of all associations between all paradigm pairs were analyzed with Spearman's correlation, and individual influencing factors were assessed with a multivariate linear regression model. RESULTS: Weak to moderate correlations among all four paradigms were found (P > 0.05), and no distinct influencing factors were identified. CONCLUSIONS: A limited association between pain modulation paradigms suggests that CPM, OA, SSP, and TSP assess distinct aspects of endogenous analgesia with different underlying physiological mechanisms.

Comparison of Feature Extraction Methods for Physiological Signals for Heat-Based Pain Recognition.

While even the most common definition of pain is under debate, pain assessment has remained the same for decades. But the paramount importance of precise pain management for successful healthcare has encouraged initiatives to improve the way pain is assessed. Recent approaches have proposed automatic pain evaluation systems using machine learning models trained with data coming from behavioural or physiological sensors. Although yielding promising results, machine learning studies for sensor-based pain recognition remain scattered and not necessarily easy to compare to each other. In particular, the important process of extracting features is usually optimised towards specific datasets. We thus introduce a comparison of feature extraction methods for pain recognition based on physiological sensors in this paper. In addition, the PainMonit Database (PMDB), a new dataset including both objective and subjective annotations for heat-induced pain in 52 subjects, is introduced. In total, five different approaches including techniques based on feature engineering and feature learning with deep learning are evaluated on the BioVid and PMDB datasets. Our studies highlight the following insights: (1) Simple feature engineering approaches can still compete with deep learning approaches in terms of performance. (2) More complex deep learning architectures do not yield better performance compared to simpler ones. (3) Subjective self-reports by subjects can be used instead of objective temperature-based annotations to build a robust pain recognition system.

To Experience or to Be Informed? Classical Conditioning Induces Nocebo Hyperalgesia even when Placebo Analgesia Is Verbally Suggested-Results of a Preliminary Study.

OBJECTIVE: To investigate whether direct experience (i.e., classical conditioning) or verbal suggestion is more important in inducing nocebo hyperalgesia, five groups (total sample size, N = 99) were studied: conditioning, congruent conditioning, incongruent conditioning, verbal suggestion, and control. METHODS: Participants in groups with conditioning experienced more intensive pain stimuli after presentation of a white circle. In the congruent conditioning group, suggestion that the circle would precede more intensive pain stimuli was additionally provided, whereas in the incongruent conditioning group, the opposite suggestion was used. Control and verbal suggestion groups received pain stimuli of one intensity; however, the latter received suggestion that a circle would precede pain stimuli of higher intensity. RESULTS: The nocebo effect was observed in all conditioning groups, regardless of the verbal suggestions used. Moreover, the experience of hyperalgesia was able to nullify the effect of the verbal suggestion of analgesia. Incongruence between verbal suggestion and pain experience produced expectancies that affected nocebo hyperalgesia. CONCLUSIONS: The results of this preliminary study suggest that direct experience seems to be more important than verbal suggestion in inducing nocebo hyperalgesia.

Preliminary Validation of a Two-Point Estimation Task for the Measurement of Sensory Dissociation in Patients with Chronic Low Back Pain.

OBJECTIVES: Sensory dissociation (SEDI), the discrepancy between perception and actual size or shape of a painful body part, is a frequently observed finding in patients with chronic low back pain. However, the current methods of evaluating SEDI have several limitations, such as a qualitative nature and weak evidence supporting their reliability. In the current study, the reliability of two versions (manual and verbal) of a novel test, a two-point estimation task (TPE), was investigated. METHODS: To perform the manual version of the task, patients estimated the distance between two tactile stimuli delivered to their back using callipers, whereas in the verbal version they verbally reported the estimated distance. RESULTS: The manual version of TPE showed greater interexaminer reliability than the verbal version, and the mean of the two repeated measurements was sufficient for reaching excellent reliability for the pain-free (intraclass correlation coefficient [ICC] = 0.91, 95% confidence interval [CI] = 0.77-0.97) and painful (ICC = 0.86, 95% CI = 0.65-0.94) sides. Intra-examiner reliability was moderate to excellent (ICC = 0.66-0.96) for the manual version performed at the pain-free and painful sides. Distribution, duration, and intensity of pain significantly predicted SEDI and accounted for 42% of the total variance (corrected R2 = 0.42, P < 0.01). CONCLUSIONS: TPE showed higher reliability coefficients compared with tools previously suggested in the literature and can therefore be used clinically and experimentally by one or more examiners. Further research is required to investigate the validity of this new test.

Deformations of abdominal muscles under experimentally induced low back pain.

PURPOSE: Low back pain (LBP) is associated with altered motor control and muscle activity; however, it remains unknown whether these changes predispose humans to injury and pain or are the consequence of ongoing nociceptive processes. In this experimental study, we aimed to use a novel ultrasound imaging technique for the measurement of lateral abdominal wall muscle activity: the tissue deformation index (TDI). METHODS: Forty-two healthy subjects (22.30 ± 1.49 years of age) were exposed to postural perturbation induced by rapid arm movement. Activity of three muscles, the transversus abdominis (TrA) and the internal and external oblique (EO), was recorded by ultrasound imaging (M-mode) with and without induction of LBP. Pain was induced by electrical stimulation applied bilaterally to the lumbar spine. RESULTS: No significant differences in the TDI between right and left sides of the body (p > 0.05) were found. Generally, muscles deformed slower with pain compared to non-painful conditions; however, only EO muscle displayed a statistically significant reduction in deformation velocity (p ≤ 0.00001). TDI for EO decreased from 0.065% per ms ( ± 0.038, 95% CI 0.057-0.074) to 0.053% per ms ( ± 0.035, 95% CI 0.046-0.061). Furthermore, characteristic inter-muscular TDI gradients were observed, directed from inner towards outer muscular layers, with TrA showing the lowest TDI and EO the highest. CONCLUSION: Experimentally induced LBP suppresses deformation of the superficial abdominal muscles and increases the variability of local/deep muscles. Further research is required to confirm these observations. These slides can be retrieved under Electronic Supplementary Material.

Body Image Measured via the Fremantle Awareness Questionnaire in Individuals With and Without Pain: A Systematic Review and Meta-Analysis.

Research suggests that pain negatively affects body image, and body image may also influence reported pain levels. This review aims to summarize the literature on differences in body image distortion between individuals with pain compared to pain-free individuals. The review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 statement and an a priori preregistered protocol. The literature was searched using 5 electronic databases. Studies assessing body image with the Fremantle Awareness Questionnaire (FAQ) in individuals with and without pain were eligible for inclusion. Screening and selection of eligible studies were performed by independent reviewers. Methodological quality was assessed with the Joanna Briggs Institute critical appraisal tool. Meta-analyses, meta-correlations, and metamean analyses were performed using random-effect models. The primary outcome was the FAQ score; secondary outcomes were reported pain variables. Data from individuals with pain (n = 2277) and without pain (n = 615) were summarized. Significant body image distortions were found in individuals with pain compared to individuals without pain. Compared to pain-free individuals, the pain group rated significantly higher in the FAQ when experiencing back pain (standardized mean differences=1.33, 95% confidence interval=.88-1.77) or other body parts (standardized mean differences=1.25, 95% confidence interval=.51-1.99). The results of meta-correlation analyses confirmed the positive relationship between body image distortion and pain intensity (r = .31), pain at rest (r = .31), or pain during movement (r = .36), but not for pain duration. A difference in mean FAQ results was observed between individuals with pain in different areas (knee and back). PERSPECTIVE: This review confirms differences in body image distortion between pain and pain-free individuals. Pain intensity was correlated with altered body perception, but not pain duration. A moderate correlation was observed between body image distortion and reported pain variables. Body image was more impaired by knee pain than back pain. REGISTERED PROTOCOL AT PROSPERO: CRD42022309937; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022309937.

Differential Effects of Thermal Stimuli in Eliciting Temporal Contrast Enhancement: A Psychophysical Study.

Offset analgesia (OA) is observed when pain relief is disproportional to the reduction of noxious input and is based on temporal contrast enhancement (TCE). This phenomenon is believed to reflect the function of the inhibitory pain modulatory system. However, the mechanisms contributing to this phenomenon remain poorly understood, with previous research focusing primarily on painful stimuli and not generalizing to nonpainful stimuli. Therefore, the aim of this study was to investigate whether TCE can be induced by noxious as well as innocuous heat and cold stimuli. Asymptomatic subjects (n = 50) were recruited to participate in 2 consecutive experiments. In the first pilot study (n = 17), the parameters of noxious and innocuous heat and cold stimuli were investigated in order to implement them in the main study. In the second (main) experiment, subjects (n = 33) participated in TCE paradigms consisting of 4 different modalities, including noxious heat (NH), innocuous heat (IH), noxious cold (NC), and innocuous cold (IC). The intensity of the sensations of each thermal modality was assessed using an electronic visual analog scale. TCE was confirmed for NH (P < .001), NC (P = .034), and IC (P = .002). Conversely, TCE could not be shown for IH (P = 1.00). No significant correlation between TCE modalities was found (r < .3, P > .05). The results suggest that TCE can be induced by both painful and nonpainful thermal stimulation but not by innocuous warm temperature. The exact underlying mechanisms need to be clarified. However, among other potential mechanisms, this may be explained by a thermo-specific activation of C-fiber afferents by IH and of A-fiber afferents by IC, suggesting the involvement of A-fibers rather than C-fibers in TCE. More research is needed to confirm a peripheral influence. PERSPECTIVE: This psychophysical study presents the observation of temporal contrast enhancement during NH, NC, and innocuous cold stimuli but not during stimulation with innocuous warm temperatures in healthy volunteers. A better understanding of endogenous pain modulation mechanisms might be helpful in explaining the underlying aspects of pain disorders.

Assessing the influence of non-ischaemic A-fiber conduction blockade on offset analgesia: an experimental study.

Offset analgesia (OA) is believed to reflect the efficiency of the endogenous pain modulatory system. However, the underlying mechanisms are still being debated. Previous research suggested both, central and peripheral mechanisms, with the latter involving the influence of specific A-delta-fibers. Therefore, this study aimed to investigate the influence of a non-ischaemic A-fiber conduction blockade on the OA response in healthy participants. A total of 52 participants were recruited for an A-fiber conduction blockade via compression of the superficial radial nerve. To monitor fiber-specific peripheral nerve conduction capacity, quantitative sensory testing was performed continuously. Before, during and after the A-fiber block, an individualized OA-paradigm was applied to the dorsum of both hands (blocked and control side were randomized). Pain intensity of each heat stimulus was evaluated by an electronic visual analogue scale. A successful A-fiber conduction blockade was achieved in thirty participants. Offset analgesia has been verified within time (before, during, after blockade), and condition (blocked and control side) (p < 0.01, d > 0.5). Repeated measurements ANOVA showed no significant interaction effects between OA within condition and time (p = 0.24, η²p = 0.05). Hence, no significant effect of A-fiber blockade was detected on OA during noxious heat stimulation. The results suggest that peripheral A-fiber afferents may play a minor role in OA compared to alternative central mechanisms or other fibers. However, further studies are needed to substantiate a central rather than peripheral influence on OA. PERSPECTIVE: This article presents the observation of offset analgesia before, during and after a successful A-fiber conduction blockade in healthy volunteers. A better understanding of the mechanisms of offset analgesia and endogenous pain modulation in general may help to explain the underlying aspects of pain disorders.

Pain memory in children: a systematic review and meta-analysis with a meta-regression.

ABSTRACT: 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.

Radiation of pain: Psychophysical evidence for a population coding mechanism.

The spread of pain across body locations remains poorly understood but may provide important insights into the encoding of sensory features of noxious stimuli by populations of neurons. In this psychophysical experiment, we hypothesized that more intense noxious stimuli would lead to spread of pain, but more intense light stimuli would not produce perceptual radiation. Fifty healthy volunteers participated in this study wherein four intensities of noxious stimuli (43, 45, 47 and 49°C) were applied to glabrous (hand) and hairy skin (forearm) skin with 5s and 10s durations. Also, four different intensities of visual stimuli displayed on the target bodily area were utilized as a control. Participants provided pain (and light) spatial extent ratings as well as pain (and light) intensity ratings. In the extent rating procedure, participants adjusted the extent of the square displayed on the screen with the extent of pain (or light) which they experienced. Pain extent ratings showed statistically significant radiation of pain indicated by 12.42× greater spatial spread of pain (pain extent) than the area of the stimulation with 49°C (p < 0.001), in contrast to visual ratings which closely approximated the size of the stimulus (1.22×). Pain radiation was more pronounced in hairy than glabrous skin (p < 0.05) and was more pronounced with longer stimulus duration (p < 0.001). Pain intensity explained, on average, only 14% of the pain radiation variability. The relative independence of the pain radiation from perceived pain intensity indicates that distinct components of population coding mechanisms may be involved in the spatial representation of pain versus intensity coding.

Association between myofascial trigger point therapy and conditioned pain modulation.

INTRODUCTION: Myofascial trigger point therapy (MTrP) is a widely used therapeutic approach, although the underlying mechanisms remain unclear. Mechanisms discussed include peripheral involvement of muscles as well as central pain modulating processes such as the conditioned pain modulation (CPM). The aim of this study was to investigate whether the analgesic response of MTrP and the analgesic response of CPM correlate in asymptomatic participants in order to identify shared underlying mechanisms of MTrP and CPM. METHOD: Both, CPM and MTrP protocols consisted of heat-based test stimuli (heat pain thresholds before and after the intervention) and pressure-based (conditioning) stimuli. Asymptomatic participants (n = 94) were randomly assigned to receive either mild, intense or no pressure stimuli (between-group design) to both the fingernail and the MTrP of the infraspinatus muscle (within-group design). Pressure stimuli at both locations (fingernail, MTrP) were applied with a pressure algometer for 120 s and continuously adjusted to maintain a constant pain intensity of mild or intense pain. All thermal stimuli were applied on the lower leg with a thermal stimulator. RESULTS: A significant correlation was shown between the analgesic effect of CPM and MTrP therapy for mild (r = 0.53, p = 0.002) and intensive stimuli (r = 0.73, p < 0.001). 17.3% of the variance of the MTrP effect were explained by CPM after mild stimulation, and 47.1% after intense stimulation. Pain-related characteristics did not explain the variance within the analgesic response using a regression analysis. CONCLUSIONS: Between the analgesic responses following MTrP and CPM paradigms, a moderate to strong correlation was observed, suggesting shared underlying mechanisms.

Spatial summation of pain is associated with pain expectations: Results from a home-based paradigm.

The purpose of this study was to reproduce the previously observed spatial summation of pain effect (SSp) using non-laboratory procedures and commercial equipment. An additional aim was to explore the association between expectations and SSp. The Cold Pressor Task (CPT) was used to induce SSp. Healthy participants (N = 68) immersed their non-dominant hands (divided into 5 segments) into cold water (CPT). Two conditions were used 1) gradual hand immersion (ascending condition) and 2) gradual hand withdrawal (descending condition). Pain intensity was measured on a Visual Analogue Scale (VAS). Psychological factors, such as the participants' expectations of pain intensity were also measured on a VAS. Results showed significant SSp (χ2(4) = 116.90, p < 0.001), reproduced with non-laboratory equipment in a home-based set-up. Furthermore, two novel findings were observed: i) there was a significant correlation between expectations and perceived pain, indicating a link between pain expectations and SSp, ii) spatial summation increased with the increase in duration exposure to the noxious stimulus (Wald χ2(8) = 80.80, p < 0.001). This study suggests that SSp is associated with pain expectations and can be formed by a mixture of excitatory and inhibitory mechanisms potentially driven by temporal characteristics of neural excitation. Moreover, this study proposes a new feasible way to induce SSp using a home-based set-up.

Psychological mechanisms of offset analgesia: The effect of expectancy manipulation.

A frequently used paradigm to quantify endogenous pain modulation is offset analgesia, which is defined as a disproportionate large reduction in pain following a small decrease in a heat stimulus. The aim of this study was to determine whether suggestion influences the magnitude of offset analgesia in healthy participants. A total of 97 participants were randomized into three groups (hypoalgesic group, hyperalgesic group, control group). All participants received four heat stimuli (two constant trials and two offset trials) to the ventral, non-dominant forearm while they were asked to rate their perceived pain using a computerized visual analogue scale. In addition, electrodermal activity was measured during each heat stimulus. Participants in both intervention groups were given a visual and verbal suggestion about the expected pain response in an hypoalgesic and hyperalgesic manner. The control group received no suggestion. In all groups, significant offset analgesia was provoked, indicated by reduced pain ratings (p < 0.001) and enhanced electrodermal activity level (p < 0.01). A significant group difference in the magnitude of offset analgesia was found between the three groups (F[2,94] = 4.81, p < 0.05). Participants in the hyperalgesic group perceived significantly more pain than the hypoalgesic group (p = 0.031) and the control group (p < 0.05). However, the electrodermal activity data did not replicate this trend (p > 0.05). The results of this study indicate that suggestion can be effective to reduce but not increase endogenous pain modulation quantified by offset analgesia in healthy participants.

Learning pain from others: a systematic review and meta-analysis of studies on placebo hypoalgesia and nocebo hyperalgesia induced by observational learning.

ABSTRACT: Observing someone experience pain relief or exacerbation after an intervention may induce placebo hypoalgesia or nocebo hyperalgesia. Understanding the factors that contribute to these effects could help in the development of strategies for optimizing treatment of chronic pain conditions. We systematically reviewed and meta-analyzed the literature on placebo hypoalgesia and nocebo hyperalgesia induced by observational learning (OL). A systematic literature search was conducted in the databases PubMed, PsycINFO, Web of Science, ScienceDirect, PsycARTICLES, Scopus, and Academic Search Ultimate. Twenty-one studies were included in the systematic review, 17 of which were suitable for meta-analysis (18 experiments; n = 764 healthy individuals). The primary end point was the standardized mean difference (SMD) for pain following placebo cues associated during OL with low vs high pain. Observational learning had a small-to-medium effect on pain ratings (SMD 0.44; 95% confidence interval [CI] 0.21-0.68; P < 0.01) and a large effect on pain expectancy (SMD 1.11; 95% CI 0.49-2.04; P < 0.01). The type of observation (in-person vs videotaped) modulated the magnitude of placebo hypoalgesia/nocebo hyperalgesia ( P < 0.01), whereas placebo type did not ( P = 0.23). Finally, OL was more effective when observers' empathic concern (but no other empathy-related factors) was higher ( r = 0.14; 95% CI 0.01-0.27; P = 0.03). Overall, the meta-analysis demonstrates that OL can shape placebo hypoalgesia and nocebo hyperalgesia. More research is needed to identify predictors of these effects and to study them in clinical populations. In the future, OL could be an important tool to help maximize placebo hypoalgesia in clinical settings.