Painful Heat Stimuli Research Articles

The Two Sides of Placebo Analgesia: Differential Functional Connectivity Reveals Mechanisms of Placebo Analgesic Response.

Previous research has demonstrated that placebo induction manipulations can reduce an individual's pain through non-specific mechanisms, such as expectancy manipulations. However, despite robust research characterizing these effects, individual differences in predicting placebo analgesic responses are not well understood. Fifty-four healthy pain-free adults over 18 (M=22.8, SD=7.82) were recruited (66.7% women). Participants completed a baseline followed by a placebo session involving the application of an inactive cream in the context of an expectancy-enhancing instruction set while undergoing a functional magnetic resonance imaging scan (fMRI). Painful heat stimuli were applied to the thenar eminence of the right palm. Stimulus intensity was individually calibrated to produce pain ratings of approximately 40 on a 100-point visual analog scale. Generalized psychophysiological interaction (gPPI) was used to assess the group differences in functional connectivity during painful stimulation compared to warmth stimulation. About 68.5% showed a reduction in pain in the placebo condition with an average decrease of 30.3%. Non-responders showed an increase in pain in the placebo condition, with an average increase of 18.6%. Repeated measures ANOVA demonstrated a significant within-subjects interaction between expectancy and responder type (F(1,49)=4.27, p=0.04, ηp2=0.08). Expected pain was significantly associated with pain in the placebo session for the responders (b=0.37, R2=0.29, p<0.001), but not for the non-responders (b=0.11, R2=0.04, p=0.42). gPPI analysis revealed three clusters exhibiting greater increases in FC in areas related to attention and sensory integration in placebo responders compared to non-responders. One cluster was identified where greater increases in functional connectivity were associated with non-responders compared to responders in regions associated with attention and motor processing. Our results provide evidence that responders and non-responders have differential behavioral and functional responses to acute pain during a placebo analgesic task.

Lower thresholds and stronger adaptation to pain in musicians reflect occupational-specific adaptations to contact heat stimulation.

Extensive audio-motor training and psychological stress can cause professional musicians acute overstrain-injury and chronic pain, resulting in damaged careers and diminished quality of life. It has also been previously shown that musicians might perceive pain differently than non-musicians. Therefore, the aim of our study was to quantify differences between musicians and non-musicians regarding their subjective responses to painful contact heat stimuli and assess how emotional traits might influence these responses. Upon completing the StateTrait-Anxiety-Depression Inventory, 15 healthy musicians and 15 healthy non-musicians from German universities received 15 noxious contact heat stimuli at the dorsal side of each hand and foot. After each stimulation, participants were asked to provide a pain rating from 0 to 10. Musicians not only reported significantly higher pain ratings after the first stimulation but also showed a significantly higher degree of habituation compared to non-musicians. Additionally, musicians showed a significantly less pronounced difference regarding the pain rating of the hands compared to the feet than non-musicians. Trait anxiety and trait depression scores had no effect on the pain rating or the habituation. The more pronounced habituation of musicians might hint at a neuroplastic nociceptive alteration in musicians. The lack of significance between the psychological traits and their effect on the pain ratings is surprising but could be a result of both participant groups having stressful careers. The findings of this report justify musicians' repetitive sensorimotor training as an important model for plasticity and contribute to a better understanding of pain perception in musicians.

Reliability of task-based fMRI in the dorsal horn of the human spinal cord

Abstract The application of functional magnetic resonance imaging (fMRI) to the human spinal cord is still a relatively small field of research and faces many challenges. Here we aimed to probe the limitations of task-based spinal fMRI at 3T by investigating the reliability of spinal cord blood oxygen level dependent (BOLD) responses to repeated nociceptive stimulation across 2 consecutive days in 40 healthy volunteers. We assessed the test–retest reliability of subjective ratings, autonomic responses, and spinal cord BOLD responses to short heat-pain stimuli (1 s duration) using the intraclass correlation coefficient (ICC). At the group level, we observed robust autonomic responses as well as spatially specific spinal cord BOLD responses at the expected location, but no spatial overlap in BOLD response patterns across days. While autonomic indicators of pain processing showed good-to-excellent reliability, both β-estimates and z-scores of task-related BOLD responses showed poor reliability across days in the target region (gray matter of the ipsilateral dorsal horn). When taking into account the sensitivity of gradient-echo echo planar imaging (GE-EPI) to draining vein signals by including the venous plexus in the analysis, we observed BOLD responses with fair reliability across days. Taken together, these results demonstrate that heat-pain stimuli as short as 1 s are able to evoke a robust and spatially specific BOLD response, which is, however, strongly variable within participants across time, resulting in low reliability in the dorsal horn gray matter. Further improvements in data acquisition and analysis techniques are thus necessary before event-related spinal cord fMRI as used here can be reliably employed in longitudinal designs or clinical settings.

Vicarious facilitation of facial responses to pain: Does the others' expression need to be painful?

Prior exposure to others' facial expressions of pain can lead to a facilitation of pain responses, including its corresponding response channel, namely facial responses to pain. It has been questioned, however, whether this vicarious pain facilitation occurs only when observing others' pain or whether the observation of other negative expressions can trigger similar facilitation of facial responses to pain. The study aimed to test this, by comparing the impact of viewing others' facial expressions of pain versus another negative expression (sadness) and two control expressions (neutral, happiness) on facial responses to pain. Participants (N = 56; 31 females), watched short video clips of computer-generated facial expressions (pain, sadness, neutral & happiness) before they received painful and non-painful heat stimuli. Facial responses were analysed using the Facial Action Coding System. In addition, subjective and autonomic responses were assessed. The prior exposure to others' expressions of pain and sadness versus neutral did not lead to significantly increased facial responses to pain. Likewise, subjective and autonomic pain responses were not facilitated. However, viewing others' expressions of happiness, consistently reduced facial as well as subjective and autonomic responses to pain compared to others' negative or neutral expressions. This dampening effect was not observed for non-painful heat. Facial and other pain responses were most strongly affected by prior exposure to others' facial expressions of happiness, which led to a pain-dampening effect. In contrast, the evidence for vicarious facilitation of pain was rather weak in the present study, with no evidence of pain-specificity. Facial responses to pain - along with subjective and autonomic responses - are reduced when observing others' expressions of happiness, demonstrating pain modulation by positive affective social signals, which may also transfer to clinical contexts.

Reliability of task-based fMRI in the dorsal horn of the human spinal cord.

The application of functional magnetic resonance imaging (fMRI) to the human spinal cord is still a relatively small field of research and faces many challenges. Here we aimed to probe the limitations of task-based spinal fMRI at 3T by investigating the reliability of spinal cord blood oxygen level dependent (BOLD) responses to repeated nociceptive stimulation across two consecutive days in 40 healthy volunteers. We assessed the test-retest reliability of subjective ratings, autonomic responses, and spinal cord BOLD responses to short heat pain stimuli (1s duration) using the intraclass correlation coefficient (ICC). At the group level, we observed robust autonomic responses as well as spatially specific spinal cord BOLD responses at the expected location, but no spatial overlap in BOLD response patterns across days. While autonomic indicators of pain processing showed good-to-excellent reliability, both β-estimates and z-scores of task-related BOLD responses showed poor reliability across days in the target region (gray matter of the ipsilateral dorsal horn). When taking into account the sensitivity of gradient-echo echo planar imaging (GE-EPI) to draining vein signals by including the venous plexus in the analysis, we observed BOLD responses with fair reliability across days. Taken together, these results demonstrate that heat pain stimuli as short as one second are able to evoke a robust and spatially specific BOLD response, which is however strongly variable within participants across time, resulting in low reliability in the dorsal horn gray matter. Further improvements in data acquisition and analysis techniques are thus necessary before event-related spinal cord fMRI as used here can be reliably employed in longitudinal designs or clinical settings.

Noninvasive neuromodulation of subregions of the human insula differentially affect pain processing and heart-rate variability: a within-subjects pseudo-randomized trial.

The insula is an intriguing target for pain modulation. Unfortunately, it lies deep to the cortex making spatially specific noninvasive access difficult. Here, we leverage the high spatial resolution and deep penetration depth of low-intensity focused ultrasound (LIFU) to nonsurgically modulate the anterior insula (AI) or posterior insula (PI) in humans for effect on subjective pain ratings, electroencephalographic (EEG) contact heat-evoked potentials, as well as autonomic measures including heart-rate variability (HRV). In a within-subjects, repeated-measures, pseudo-randomized trial design, 23 healthy volunteers received brief noxious heat pain stimuli to the dorsum of their right hand during continuous heart-rate, electrodermal, electrocardiography and EEG recording. Low-intensity focused ultrasound was delivered to the AI (anterior short gyrus), PI (posterior longus gyrus), or under an inert Sham condition. The primary outcome measure was pain rating. Low-intensity focused ultrasound to both AI and PI similarly reduced pain ratings but had differential effects on EEG activity. Low-intensity focused ultrasound to PI affected earlier EEG amplitudes, whereas LIFU to AI affected later EEG amplitudes. Only LIFU to the AI affected HRV as indexed by an increase in SD of N-N intervals and mean HRV low-frequency power. Taken together, LIFU is an effective noninvasive method to individually target subregions of the insula in humans for site-specific effects on brain biomarkers of pain processing and autonomic reactivity that translates to reduced perceived pain to a transient heat stimulus.

Examining Reactivity and Recovery Patterns of Pain-Evoked Cortisol and Alpha-Amylase Trajectories: Relations Between Psychological Markers of Risk and Resilience

Chronic low back pain (cLBP) is one of the leading causes of disability globally and represents an enormous burden to aging adults. While numerous factors contribute to cLBP, dysregulation in the hypothalamic-pituitary-adrenal axis and autonomic nervous system functioning have been implicated in its pathogenesis. It is well documented that negative psychological states can modulate biological stress responsivity in chronic pain; however, little is known regarding the influence of positive psychological factors in this relationship. The aim of this study was to examine the association between psychological risk and resilience factors with patterns of physiological stress reactivity and recovery in 60 older adults with cLBP. Participants completed measures of hope, optimism, pain catastrophizing, and perceived stress, and underwent psychophysical pain testing assessing responses to painful pressure, heat, and cold stimuli. Salivary samples were obtained prior to pain induction and at 7 time points spanning 90 minutes after pain testing terminated. To examine reactivity and recovery profiles in hypothalamic-pituitary-adrenal axis and autonomic nervous system function, samples were assayed for cortisol and alpha-amylase, respectively. Results revealed higher levels of hope and optimism were associated with increased cortisol reactivity (p’s < .003) and more rapid recovery (p’s = .001). Further, pain catastrophizing and perceived stress were associated with cortisol reactivity, with lower levels of these factors predicting larger increases in cortisol from baseline to peak levels (p’s < .04). No significant differences in reactivity or recovery patterns emerged for alpha-amylase. Overall, findings highlight the role of psychological risk and resilience factors in modulating physiological stress reactivity. PerspectiveThis article investigated whether psychosocial risk and resilience factors were associated with stress reactivity and recovery in response to laboratory-based pain testing in older adults with chronic low back pain. Results indicate that high resilience factors may be protective by modulating adrenocortical reactivity and recovery profiles.

Low-Intensity Focused Ultrasound to the Human Dorsal Anterior Cingulate Attenuates Acute Pain Perception and Autonomic Responses.

The dorsal anterior cingulate cortex (dACC) is a critical brain area for pain and autonomic processing, making it a promising noninvasive therapeutic target. We leverage the high spatial resolution and deep focal lengths of low-intensity focused ultrasound (LIFU) to noninvasively modulate the dACC for effects on behavioral and cardiac autonomic responses using transient heat pain stimuli. A N = 16 healthy human volunteers (6 M/10 F) received transient contact heat pain during either LIFU to the dACC or Sham stimulation. Continuous electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal response (EDR) were recorded. Outcome measures included pain ratings, heart rate variability, EDR response, blood pressure, and the amplitude of the contact heat-evoked potential (CHEP).LIFU reduced pain ratings by 1.09 ± 0.20 points relative to Sham. LIFU increased heart rate variability indexed by the standard deviation of normal sinus beats (SDNN), low-frequency (LF) power, and the low-frequency/high-frequency (LF/HF) ratio. There were no effects on the blood pressure or EDR. LIFU resulted in a 38.1% reduction in the P2 CHEP amplitude. Results demonstrate LIFU to the dACC reduces pain and alters autonomic responses to acute heat pain stimuli. This has implications for the causal understanding of human pain and autonomic processing in the dACC and potential future therapeutic options for pain relief and modulation of homeostatic signals.

Better safe than sorry?-On the influence of learned safety on pain perception.

The experience of threat was found to result-mostly-in increased pain, however it is still unclear whether the exact opposite, namely the feeling of safety may lead to a reduction of pain. To test this hypothesis, we conducted two between-subject experiments (N = 94; N = 87), investigating whether learned safety relative to a neutral control condition can reduce pain, while threat should lead to increased pain compared to a neutral condition. Therefore, participants first underwent either threat or safety conditioning, before entering an identical test phase, where the previously conditioned threat or safety cue and a newly introduced visual cue were presented simultaneously with heat pain stimuli. Methodological changes were performed in experiment 2 to prevent safety extinction and to facilitate conditioning in the first place: We included additional verbal instructions, increased the maximum length of the ISI and raised CS-US contingency in the threat group from 50% to 75%. In addition to pain ratings and ratings of the visual cues (threat, safety, arousal, valence, and contingency), in both experiments, we collected heart rate and skin conductance. Analysis of the cue ratings during acquisition indicate successful threat and safety induction, however results of the test phase, when also heat pain was administered, demonstrate rapid safety extinction in both experiments. Results suggest rather small modulation of subjective and physiological pain responses following threat or safety cues relative to the neutral condition. However, exploratory analysis revealed reduced pain ratings in later trials of the experiment in the safety group compared to the threat group in both studies, suggesting different temporal dynamics for threat and safety learning and extinction, respectively. Perspective: The present results demonstrate the challenge to maintain safety in the presence of acute pain and suggest more research on the interaction of affective learning mechanism and pain processing.

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.

Virtual reality to understand pain-associated approach behaviour: a proof-of-concept study

Pain-associated approach and avoidance behaviours are critically involved in the development and maintenance of chronic pain. Empirical research suggests a key role of operant learning mechanisms, and first experimental paradigms were developed for their investigation within a controlled laboratory setting. We introduce a new Virtual Reality paradigm to the study of pain-related behaviour and investigate pain experiences on multiple dimensions. The paradigm evaluates the effects of three-tiered heat-pain stimuli applied contingent versus non-contingent with three types of arm movements in naturalistic virtual sceneries. Behaviour, self-reported pain-related fear, pain expectancy and electrodermal activity were assessed in 42 healthy participants during an acquisition phase (contingent movement-pain association) and a modification phase (no contingent movement-pain association). Pain-associated approach behaviour, as measured by arm movements followed by a severe heat stimulus, quickly decreased in-line with the arm movement-pain contingency. Slower effects were observed in fear of movement-related pain and pain expectancy ratings. During the subsequent modification phase, the removal of the pain contingencies modified all three indices. In both phases, skin conductance responses resemble the pattern observed for approach behaviour, while skin conductance levels equal the pattern observed for the self-ratings. Our findings highlight a fast reduction in approach behaviour in the face of acute pain and inform about accompanying psychological and physiological processes. We discuss strength and limitations of our paradigm for future investigations with the ultimate goal of gaining a comprehensive understanding of the mechanisms involved in chronic pain development, maintenance, and its therapy.

Paradoxical heat sensation as a manifestation of thermal hypesthesia: a study of 1090 patients with lesions of the somatosensory system.

Paradoxical heat sensation (PHS) is the perception of warmth when the skin is cooled. Paradoxical heat sensation rarely occurs in healthy individuals but more frequently in patients suffering from lesions or disease of the peripheral or central nervous system. To further understand mechanisms and epidemiology of PHS, we evaluated the occurrence of PHS in relation to disease aetiology, pain levels, quantitative sensory testing parameters, and Neuropathic Pain Symptom Inventory (NPSI) items in patients with nervous system lesions. Data of 1090 patients, including NPSI scores from 404 patients, were included in the analysis. We tested 11 quantitative sensory testing parameters for thermal and mechanical detection and pain thresholds, and 10 NPSI items in a multivariate generalised linear model with PHS, aetiology, and pain (yes or no) as fixed effects. In total, 30% of the neuropathic patients reported PHS in contrast to 2% of healthy individuals. The frequency of PHS was not linked to the presence or intensity of pain. Paradoxical heat sensation was more frequent in patients living with polyneuropathy compared with central or unilateral peripheral nerve lesions. Patients who reported PHS demonstrated significantly lower sensitivity to thermal perception, with lower sensitivity to normally painful heat and cold stimuli. Neuropathic Pain Symptom Inventory scores were lower for burning and electric shock-like pain quality for patients with PHS. Our findings suggest that PHS is associated with loss of small thermosensory fibre function normally involved in cold and warm perception. Clinically, presence of PHS could help screening for loss of small fibre function as it is straightforward to measure or self-reported by patients.

The autonomic and nociceptive response to acute experimental stress is impaired in people with knee osteoarthritis: A preliminary study

ObjectiveAlterations in autonomic function are evident in some chronic pain conditions but have not been thoroughly examined in people with osteoarthritis (OA). The study aimed to examine resting autonomic nervous system (ANS) function in people with knee OA, and the response of the autonomic and nociceptive systems to acute stress. MethodsA preliminary cross-sectional study was undertaken involving people with knee OA (n = 14), fibromyalgia (n = 13), and pain-free controls (n = 15). The sympathetic and parasympathetic components of the ANS were assessed through measures of pre-ejection period (PEP), skin conductance level (SCL), and high frequency heart rate variability (HF HRV). The nociceptive system was assessed through pain ratings associated with a tonic heat pain stimulus. In separate sessions, ANS and heat pain measures were assessed at rest and in response to nociceptive and mental arithmetic stressors. ResultsThe knee OA group showed reduced HF HRV at rest and reduced modulation in response to stress. Resting PEP and SCL were normal in the knee OA group but PEP modulation was impaired in both chronic pain groups during nociceptive stress. The expected reduction in tonic heat pain ratings in response to stress was lacking in the knee OA and FM groups. ConclusionPreliminary evidence shows impaired parasympathetic nervous system function at rest and in response to nociceptive and mental stress in people with knee OA, with some evidence of altered sympathetic nervous system function. Impaired ANS function could contribute to ongoing pain experienced, and interventions that target ANS function could be beneficial.

Neural underpinnings of preferential pain learning and the modulatory role of fear.

Due to its unique biological relevance, pain-related learning might differ from learning from other aversive experiences. This functional magnetic resonance imaging study compared neural mechanisms underlying the acquisition and extinction of different threats in healthy humans. We investigated whether cue-pain associations are acquired faster and extinguished slower than cue associations with an equally unpleasant tone. Additionally, we studied the modulatory role of stimulus-related fear. Therefore, we used a differential conditioning paradigm, in which somatic heat pain stimuli and unpleasantness-matched auditory stimuli served as US. Our results show stronger acquisition learning for pain- than tone-predicting cues, which was augmented in participants with relatively higher levels of fear of pain. These behavioral findings were paralleled by activation of brain regions implicated in threat processing (insula, amygdala) and personal significance (ventromedial prefrontal cortex). By contrast, extinction learning seemed to be less dependent on the threat value of the US, both on the behavioral and neural levels. Amygdala activity, however, scaled with pain-related fear during extinction learning. Our findings on faster and stronger (i.e. "preferential") pain learning and the role of fear of pain are consistent with the biological relevance of pain and may be relevant to the development or maintenance of chronic pain.

Cognitive fatigue weakens the effects of distraction on pain.

Perceived pain can be viewed because of a competition between nociceptive inputs and other competing goals, such as performing a demanding cognitive task. Task performance, however, suffers when cognitively fatigued. We therefore predicted that cognitive fatigue would weaken the pain-reducing effects of performing a concurrent cognitive task, which would indicate a causal link between fatigue and heightened pain sensitivity. In this study, 2 groups of pain-free adults performed cognitive tasks while receiving painful heat stimuli. In 1 group, we induced cognitive fatigue before performing the tasks. We found that fatigue led to more pain and worse performance when the task was demanding, suggesting that fatigue weakens one's ability to distract from pain. These findings show that cognitive fatigue can impair performance on subsequent tasks and that this impairment can lower a person's ability to distract from and reduce their pain.

The Influence of Children’s Pain-Related Attention Shifting Ability and Pain Catastrophizing Upon Negatively Biased Pain Memories in Healthy School Children

The current study investigated the influence of children’s ability to flexibly shift attention toward and away from pain information on the development of negatively biased pain memories, thereby employing a direct measure of attention control reliant on behavioral responses in the context of pain (ie, an attention switching task). The direct influence of children’s attention-shifting ability and pain catastrophizing as well as the moderating role of this shifting ability in the relationship between pain catastrophizing and the development of negatively biased pain memories was examined. Healthy school children (N = 41; 9–15 years old) received painful heat stimuli and completed measures of state and trait pain catastrophizing. They then performed an attention-switching task wherein they had to shift attention between personally relevant pain-related and neutral cues. Two weeks after the painful task, children’s pain-related memories were elicited via telephone. Findings indicated that children’s reduced ability to disengage attention away from pain information predicted more fear memory bias 2 weeks later. Children’s pain-related attention-shifting ability did not moderate the relationship between children’s pain catastrophizing and negatively biased pain memories. Findings highlight the contribution of children’s attention control skills in the development of negatively biased pain memories. PerspectiveResults of the current study indicate that children with a reduced ability to shift attention away from pain information are at risk for developing negatively biased pain memories. Findings can inform interventions to minimize the development of these maladaptive negatively biased pain memories by targeting pain-relevant attention control skills in children.

Trial of a Trivial Quantitative Heat-Pain Stimulus for Detecting Severe Loss of Nociception.

Loss of nociception (LON) at the feet of persons with diabetes mellitus develops gradually over years and remains asymptomatic until the first painless diabetic foot ulceration (DFU). Severe LON with pain insensitivity can be diagnosed with a mechanical (pinprick) pain stimulus of 512-mN force. A comparable "suprathreshold" heat-pain stimulus may have the same potential. A six-second, 51°C heat-pain stimulus delivered on a 38.5-mm² spot by a commercial medical device (bite away®, to treat insect bites) was explored in a prospective cross-sectional diagnostic accuracy study to detect DFU-related LON. Seventy-two participants were studied: 12 with and 30 without diabetic neuropathy according to the conventional criteria, and 30 patients with a history of painless DFU (indicative of end-stage LON, reference standard). The feet were stimulated at the plantar and dorsal sides. A palmar surface was stimulated for control purposes. Participants scored stimulated pain intensity 0 to 10 on a numerical rating scale. At hands, pain intensity was rated six on average by all participants. Persons without neuropathy scored 7 (0-10), median (range), at the plantar side and 8.5 (2-10) at the dorsal side of the foot, while those with DFU scored 0 (0-8) and 0 (0-10), respectively. A pain response of 0 at the foot dorsum detected DFU-related LON with a sensitivity of 65% (specificity, 100%; positive and negative predictive values, 100% and 96%, respectively). Due to its high specificity, the test seems advantageous for diagnostic purposes, complementary to current screening tests.

Effect of spinal anesthesia-induced deafferentation on pain processing in healthy male volunteers: A task-related fMRI study.

Spinal anesthesia causes short-term deafferentation and alters the crosstalk among brain regions involved in pain perception and pain modulation. In the current study, we examined the effect of spinal anesthesia on pain response to noxious thermal stimuli in non-deafferented skin areas using a functional magnetic resonance imaging (fMRI) paradigm. Twenty-two healthy subjects participated in the study. We performed a task-based fMRI study using a randomized crossover design. Subjects were scanned under two conditions (spinal anesthesia or control) at two-time points: before and after spinal anesthesia. Spinal anesthesia resulted in sensory loss up to dermatome Th6. Calibrated heat-pain stimuli were administered to the right forearm (C8-Th1) using a box-car design (blocks of 10s on/25s off) during MRI scanning. Pain perception was measured using a visual analogue scale (1-100) at the beginning and the end of each session. Generalized estimating equations were used to examine the effect of intervention by time by order on pain scores. Similarly, higher-level effects were tested with appropriate general linear models (accounting for within-subject variations in session and time) to examine: (1) Differences in BOLD response to pain stimulus under spinal anesthesia versus control; and (2) Effects of spinal anesthesia on pain-related modulation of the cerebral activation. Complete fMRI data was available for eighteen participants. Spinal anesthesia was associated with moderate pain score increase. Significant differences in brain response to noxious thermal stimuli were present in comparison of spinal versus control condition (post-pre). Spinal condition was associated with higher BOLD signal in the bilateral inferior parietal lobule and lower BOLD signal in bilateral postcentral and precentral gyrus. Within the angular regions, we observed a positive correlation between pain scores and BOLD signal. These observations were independent from order effect (whether the spinal anesthesia was administered in the first or the second visit). However, we did observe order effect on brain regions including medial prefrontal regions, possibly related to anticipation of the experience of spinal anesthesia. The loss of sensory and motor activity caused by spinal anesthesia has a significant impact on brain regions involved in the sensorimotor and cognitive processing of noxious heat pain stimuli. Our results indicate that the anticipation or experience of a strong somatosensory response to the spinal intervention might confound and contribute to increased sensitivity to cognitive pain processing. Future studies must account for individual differences in subjective experience of pain sensation within the experimental context.

Distraction from pain depends on task demands and motivation

Pain captures attention automatically, yet we can inhibit pain when we are motivated to perform other tasks. Previous studies show that engaging in a cognitively demanding task reduces pain compared with a task that is minimally demanding, yet the effects of motivation on this pain-reducing effect remain largely unexplored. In this study, we hypothesized that motivating people to engage in a task with high demands would lead to more cognitive resources directed toward the task, thereby amplifying its pain-reducing effects. On different trials, participants performed an easy (left-right arrow discrimination) or demanding (2-back) cognitive task while receiving nonpainful or painful heat stimuli. In half of the trials, monetary rewards were offered to motivate participants to engage and perform well in the task. Results showed an interaction between task demands and rewards, whereby offering rewards strengthened the pain-reducing effect of a distracting task when demands were high. This effect was reinforced by increased 2-back performance when rewards were offered, indicating that both task demands and motivation are necessary to inhibit pain. When task demands are low, motivation to engage in the task will have little impact on pain because performance cannot further increase. When motivation is low, participants will spend minimal effort to perform well in the task, thus hindering the pain-reducing effects of higher task demands. These findings suggest that the pain-reducing properties of distraction can be optimized by carefully calibrating the demands and motivational value of the task.

The relation between children's attention bias to pain and children's pain-related memory biases is moderated by parental narrative style

Children's heightened attention to pain and parental narrative style have been linked to the development of negatively-biased pain memories in children (i.e., recalling higher levels of pain and fear than initially reported, which robustly predicts maladaptive pain outcomes). However, the interplay between child attention bias and parental narrative style remains to be assessed. This study aims to fill this gap using enhanced paradigms assessing children's cognitive biases for cues signaling actual pain. Healthy school children (N = 63; 9–15 years old) received painful heat stimuli while performing a spatial cueing task measuring attention bias to cues signaling actual pain. Parent-child interaction upon completion of the painful task, was coded for parental narrative style (i.e., elaboration, repetition and evaluation). Children's pain-related memories were elicited two weeks later. Findings indicated that children showed an attention bias to cues signaling pain. Furthermore, children who were hypervigilant to pain cues benefitted from parents elaborating more about the pain experience, while children who avoided pain cues developed more negatively-biased pain memories if parents had a more elaborative style compared to a more evaluative parental style. In conclusion, this study suggests that optimal ways to talk about children's pain depend upon child characteristics (i.e., children's attention bias to pain).