An Experimental and Clinical Physiological Signal Dataset for Automated Pain Recognition.

Access to large amounts of data is essential for successful machine learning research. However, there is insufficient data for many applications, as data collection is often challenging and time-consuming. The same applies to automated pain recognition, where algorithms aim to learn associations between a level of pain and behavioural or physiological responses. Although machine learning models have shown promise in improving the current gold standard of pain monitoring (self-reports) only a handful of datasets are freely accessible to researchers. This paper presents the PainMonit Dataset for automated pain detection using physiological data. The dataset consists of two parts, as pain can be perceived differently depending on its underlying cause. (1) Pain was triggered by heat stimuli in an experimental study during which nine physiological sensor modalities (BVP, 2×EDA, skin temperature, ECG, EMG, IBI, HR, respiration) were recorded from 55 healthy subjects. (2) Eight modalities (2×BVP, 2×EDA, EMG, skin temperature, respiration, grip) were recorded from 49 participants to assess their pain during a physiotherapy session.

Assessing the Influence of Nonischemic 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 nonischemic 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 sides were randomized). The pain intensity of each heat stimulus was evaluated by an electronic visual analog scale. A successful A-fiber conduction blockade was achieved in thirty participants. OA has been verified within time (before, during, and after blockade) and condition (blocked and control side) (P < .01, d > .5). Repeated measurements analysis of variance showed no significant interaction effects between OA within condition and time (P = .24, η²p = .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 with 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 OA before, during, and after a successful A-fiber conduction blockade in healthy volunteers. A better understanding of the mechanisms of OA and endogenous pain modulation, in general, may help to explain the underlying aspects of pain disorders.

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.

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.

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

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 (27 females, 23 males, ages 14-44) participated in this study wherein noxious stimuli (43, 45, 47 and 49°C) were applied to glabrous (hand) and hairy skin (forearm) skin with 5s and 10s durations. Also, 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 only 14% of the pain radiation variability. The relative independence of the pain radiation from pain intensity indicates that distinct components of population coding mechanisms may be involved in the spatial representation of pain versus intensity coding.

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.

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.

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.

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.

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.

No Sufficient Evidence for an Immediate Hypoalgesic Effect of Spinal Manual Therapy on Pressure Pain Thresholds in Asymptomatic and Chronic Pain Populations: A Systematic Review and Meta-Analysis.

OBJECTIVE: Spinal manual therapy (SMT) is often used to treat patients with spinal disorders; however, the underlying mechanisms of SMT are not fully understood. This systematic review and meta-analysis investigates the effect of SMT compared with sham treatment or no intervention on local or remote (segmental or non-segmental) pressure pain thresholds (PPTs) in patients with chronic musculoskeletal conditions and people who are pain free. METHODS: A systematic search was conducted in the PubMed, Cochrane Library, Web of Science, and CINAHL databases. Randomized controlled trials investigating the effect of SMT on PPTs in patients with chronic musculoskeletal conditions and in people who were pain free were included. Quality assessment and evidence synthesis were performed according to Cochrane Handbook recommendations. A meta-analysis was performed using standardized mean difference and 95% CIs. RESULTS: Twenty-two reports were included in the present review. There were no significant results for an immediate effect of SMT on local (low certainty of evidence), remote (segmental) (low certainty of evidence), and remote (non-segmental) (low certainty of evidence) PPTs in patients with chronic pain as well as on local (moderate certainty of evidence) and remote (segmental) (low certainty of evidence) PPTs in people who were pain free. A small but significant effect (standardized mean difference = 0.26; 95% CI = 0.01 to 0.51; low certainty of evidence) was observed on remote (non-segmental) PPTs in people who were pain free, which was not considered a meaningful effect size. CONCLUSION: No immediate, consistent, or meaningful hypoalgetic effect of SMT was shown on PPTs on various body areas. Involvement of spinal or supraspinal underlying mechanisms were, therefore, not confirmed via PPTs but should still be investigated using methods designed to assess central nervous pain processing. IMPACT: No consistent and meaningful hypoalgesic effects of spinal manual therapy were demonstrated on PPTs in participants who were pain free and in patients with chronic musculoskeletal disorders.

Spatial Tuning in Nociceptive Processing Is Driven by Attention.

When the source of nociception expands across a body area, the experience of pain increases due to the spatial integration of nociceptive information. This well-established effect is called spatial summation of pain (SSp) and has been the subject of multiple investigations. Here, we used cold-induced SSp to investigate the effect of attention on the spatial tuning of nociceptive processing. Forty pain-free volunteers (N = 40, 20 females) participated in this experiment. They took part in an SSp paradigm based on three hand immersions into cold water (5°C): Participants either immersed the radial segment ("a"), ulnar segment ("b") or both hand segments ("a+b") and provided overall pain ratings. In some trials based on "a+b" immersions, they were also asked to provide divided (ie, first pain in "a" then in "b"; or reversed) and directed attention ratings (ie, pain only in "a" or "b"). Results confirmed a clear SSp effect in which reported pain during immersions of "a" or "b" was less intense than pain during immersions of "a+b" (P < .001). Data also confirmed that spatial tuning was altered. SSp was abolished when participants provided two ratings in a divided fashion (P < .001). Furthermore, pain was significantly lower when attention was directed only to one segment ("a" OR "b") during "a+b" immersion (P < .001). We conclude that spatial tuning is dynamically driven by attention as reflected in abolished SSp. Directed attention was sufficient to focus spatial tuning and abolish SSp. Results support the role of cognitive processes such as attention in spatial tuning. PERSPECTIVE: This article presents experimental investigation of spatial tuning in pain and offers mechanistic insights of contiguous spatial summation of pain in healthy volunteers. Depending on how pain is evaluated in terms of attentional derivative (overall pain, directed, divided attention) the pain is reduced and spatial summation abolished.

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.

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.

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.

Effects of stimulation area and temperature rates on offset analgesia.

Introduction: Offset analgesia describes the effect of a slightly reduced nociceptive stimulus, resulting in a disproportionate large reduction in the pain perception. This effect may be associated with descending pain inhibition, but parameters influencing this phenomenon are poorly understood. Objectives: In this study, 2 separate experiments were conducted to investigate both, the spatial aspects of offset analgesia and the influence of different rates of temperature rise. Methods: In both experiments, 29 healthy participants received individualized and heat-based offset analgesia paradigms applied to the forearm, with continuous assessment of pain intensity. In experiment 1, offset analgesia paradigms with 3 different rates of temperature rise were applied, whereas in experiment 2, offset analgesia paradigms with 2 different heat application areas were used. Results: The results of experiment 1 showed that different temperature rates had no effect on the offset analgesia response (P > 0.05). Experiment 2, however, showed the influence of the size of a stimulated area on offset analgesia (P = 0.009), which can be explained mainly by the influence of spatial summation of pain and habituation processes. Conclusions: The study showed a lack of influence of different temperature rates on offset analgesia; however, spatial aspects of offset analgesia could be identified. These are most likely based on spatial summation of pain and altered adaptation to pain.

Is Pain Contagious? Innocuous Stimulation Can be Transformed Into the Pain Experience by Observational Learning.

Studies indicate that classical and operant conditioning have potential to play a role in the formation of the allodynic effect. Only a few studies have examined the role of observational learning in pain induction. Due to some methodological challenges, evidence that the allodynic effect can be learned through observation is limited. In the present study, healthy participants (n = 88) received 2 series of innocuous electrocutaneous stimuli: at the beginning of the study and after observation of a model who rated all the stimuli as painful. Participants and the model rated all the stimuli alternately (real-time group), or the participant first observed the model and then rated the stimuli, while the model stayed in (post-hoc+ group) or left (post-hoc- group) the laboratory. There was no model in the control group. The study demonstrated that allodynia can be induced by observational learning. Furthermore, this effect was shown to be similar, regardless of whether stimuli were received during the observation of the model and rated immediately afterwards, or when the observation and stimuli reception were time-separated. The mere presence of the model during the stimuli reception also did not affect the magnitude of this effect. This research may contribute to our understanding of the mechanisms of chronic pain development and assist in the development of suitable treatment for it. PERSPECTIVE: This article presents study results on the role of observational learning in allodynia induction without tissue injury. The results may contribute to our understanding of the mechanisms of chronic pain development and assist in the development of suitable treatment for it.

To Calibrate or not to Calibrate? A Methodological Dilemma in Experimental Pain Research.

To calibrate or not to calibrate? This question is raised by almost everyone designing an experimental pain study with supra-threshold stimulation. The dilemma is whether to individualize stimulus intensity to the pain threshold / supra-threshold pain level of each participant or whether to provide the noxious stimulus at a fixed intensity so that everyone receives the identical input. Each approach has unique pros and cons which need to be considered to i) accurately design an experiment, ii) enhance statistical inference in the given data and, iii) reduce bias and the influence of confounding factors in the individual study e.g., body composition, differences in energy absorption and previous experience. Individualization requires calibration, a procedure already irritating the nociceptive system but allowing to match the pain level across individuals. It leads to a higher variability of the stimulus intensity, thereby influencing the encoding of "noxiousness" by the central nervous system. Results might be less influenced by statistical phenomena such as ceiling/floor effects and the approach does not seem to rise ethical concerns. On the other hand, applying a fixed (standardized) intensity reduces the problem of intensity encoding leading to a large between-subjects variability in pain responses. Fixed stimulation intensities do not require pre-exposure. It can be proposed that one method is not preferable over another, however the choice depends on the study aim and the desired level of external validity. This paper discusses considerations for choosing the optimal approach for experimental pain studies and provides recommendations for different study designs. PERSPECTIVE: To calibrate pain or not? This dilemma is related to almost every experimental pain research. The decision is a trade-off between statistical power and greater control of stimulus encoding. The article decomposes both approaches and presents the pros and cons of either approach supported by data and simulation experiment.

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.