Brief Self-Compassion Training Alters Neural Responses to Evoked Pain for Chronic Low Back Pain: A Pilot Study.

OBJECTIVE: Self-compassion meditation, which involves compassion toward the self in moments of suffering, shows promise for improving pain-related functioning, but its underlying mechanisms are unknown. This longitudinal, exploratory pilot study investigated the effects of a brief (eight contact hours, two weeks of home practice) self-compassion training on pain-related brain processing in chronic low back pain (cLBP). METHODS: We evaluated functional magnetic resonance imaging (fMRI) response to evoked pressure pain and its anticipation during a self-compassionate state and compared altered brain responses following training with changes on self-reported measures of self-compassion (Self-Compassion Scale [SCS]), interoceptive awareness (Multidimensional Assessment of Interoceptive Awareness [MAIA]), and clinical pain intensity. RESULTS: In a sample of participants with cLBP (N = 20 total, N = 14 with complete longitudinal data) who underwent self-compassion training, we observed reduced clinical pain intensity and disability (P < 0.01) and increased trait self-compassion and interoceptive awareness (all P < 0.05) following training. Evoked pressure pain response in the right temporo-parietal junction (TPJ) was reduced following training, and decreases were associated with reduced clinical pain intensity. Further, increased fMRI responses to pain anticipation were observed in the right dorsolateral prefrontal cortex (dlPFC) and ventral posterior cingulate cortex (vPCC), and these increases were associated with mean post-training changes in SCS scores and scores from the body listening subscale of the MAIA. DISCUSSION: These findings, though exploratory and lacking comparison with a control condition, suggest that self-compassion training supports regulation of pain through the involvement of self-referential (vPCC), salience-processing (TPJ), and emotion regulatory (dlPFC) brain areas. The results also suggest that self-compassion could be an important target in the psychotherapeutic treatment of cLBP, although further studies using controlled experimental designs are needed to determine the specificity of these effects.

Anticipation and violated expectation of pain are influenced by trait rumination: An fMRI study.

Rumination - as a stable tendency to focus repetitively on feelings related to distress - represents a transdiagnostic risk factor. Theories suggest altered emotional information processing as the key mechanism of rumination. However, studies on the anticipation processes in relation to rumination are scarce, even though expectation in this process is demonstrated to influence the processing of emotional stimuli. In addition, no published study has investigated violated expectation in relation to rumination yet. In the present study we examined the neural correlates of pain anticipation and perception using a fear conditioning paradigm with pain as the unconditioned stimulus in healthy subjects (N = 30). Rumination was assessed with the 10-item Ruminative Response Scale (RRS). Widespread brain activation - extending to temporal, parietal, and occipital lobes along with activation in the cingulate cortex, insula, and putamen - showed a positive correlation with rumination, supporting our hypothesis that trait rumination influences anticipatory processes. Interestingly, with violated expectation (when an unexpected, non-painful stimulus follows a pain cue compared to when an expected, painful stimulus follows the same pain cue) a negative association between rumination and activation was found in the posterior cingulate cortex, which is responsible for change detection in the environment and subsequent behavioral modification. Our results suggest that rumination is associated with increased neural response to pain perception and pain anticipation, and may deteriorate the identification of an unexpected omission of aversive stimuli. Therefore, targeting rumination in cognitive behavioral therapy of chronic pain could have a beneficial effect.

Effect of movement-related pain on behaviour and corticospinal excitability changes associated with arm movement preparation.

KEY POINTS: Experimental pain or its anticipation influence motor preparation processes as well as upcoming movement execution, but the underlying physiological mechanisms remain unknown. Our results showed that movement-related pain modulates corticospinal excitability during motor preparation. In accordance with the pain adaptation theory, corticospinal excitability was higher when the muscle has an antagonist (vs. an agonist) role for the upcoming movement associated with pain. Anticipation of movement-related pain also affects motor initiation and execution, with slower movement initiation (longer reaction times) and faster movement execution compared to movements that do not evoke pain. These results confirm the implementation of protective strategies during motor preparation known to be relevant for acute pain, but which may potentially have detrimental long-term consequences and lead to the development of chronic pain. ABSTRACT: When a movement repeatedly generates pain, we anticipate movement-related pain and establish self-protective strategies during motor preparation, but the underlying mechanisms remains poorly understood. The current study investigated the effect of movement-related pain anticipation on the modulation of behaviour and corticospinal excitability during the preparation of arm movements. Participants completed an instructed-delay reaction-time (RT) task consisting of elbow flexions and extensions instructed by visual cues. Nociceptive laser stimulations (unconditioned stimuli) were applied to the lateral epicondyle during movement execution in a specific direction (CS+) but not in the other (CS-), depending on experimental group. During motor preparation, transcranial magnetic stimulation was used to measure corticospinal excitability in the biceps brachii (BB). RT and peak end-point velocity were also measured. Neurophysiological results revealed an opposite modulation of corticospinal excitability in BB depending on whether it plays an agonist (i.e. flexion) or antagonist (i.e. extension) role for the CS+ movements (P < 0.001). Moreover, behavioural results showed that for the CS+ movements RT did not change relative to baseline, whereas the CS- movements were initiated more quickly (P = 0.023) and the CS+ flexion movements were faster relative to the CS- flexion movements (P < 0.001). This is consistent with the pain adaptation theory which proposes that in order to protect the body from further pain, agonist muscle activity is reduced and antagonist muscle activity is increased. If these strategies are initially relevant and lead to short-term pain alleviation, they may potentially have detrimental long-term consequences and lead to the development of chronic pain.

Deep brain stimulation of the ventral striatal area for poststroke pain syndrome: a magnetoencephalography study.

Poststroke pain syndrome (PSPS) is an often intractable disorder characterized by hemiparesis associated with unrelenting chronic pain. Although traditional analgesics have largely failed, integrative approaches targeting affective-cognitive spheres have started to show promise. Recently, we demonstrated that deep brain stimulation (DBS) of the ventral striatal area significantly improved the affective sphere of pain in patients with PSPS. In the present study, we examined whether electrophysiological correlates of pain anticipation were modulated by DBS that could serve as signatures of treatment effects. We recorded event-related fields (ERFs) of pain anticipation using magnetoencephalography (MEG) in 10 patients with PSPS preoperatively and postoperatively in DBS OFF and ON states. Simple visual cues evoked anticipation as patients awaited a painful (PS) or nonpainful stimulus (NPS) to the nonaffected or affected extremity. Preoperatively, ERFs showed no difference between PS and NPS anticipation to the affected extremity, possibly due to loss of salience in a network saturated by pain experience. DBS significantly modulated the early N1, consistent with improvements in affective networks involving restoration of salience and discrimination capacity. Additionally, DBS suppressed the posterior P2 (aberrant anticipatory anxiety) while enhancing the anterior N1 (cognitive and emotional regulation) in responders. DBS-induced changes in ERFs could potentially serve as signatures for clinical outcomes. NEW & NOTEWORTHY We examined the electrophysiological correlates of pain affect in poststroke pain patients who underwent deep brain stimulation (DBS) targeting the ventral striatal area under a randomized, controlled trial. DBS significantly modulated early event-related components, particularly N1 and P2, measured with magnetoencephalography during a pain anticipatory task, compared with baseline and the DBS-OFF condition, pointing to possible mechanisms of action. DBS-induced changes in event-related fields could potentially serve as biomarkers for clinical outcomes.

Heightened brain response to pain anticipation in high-functioning adults with autism spectrum disorder.

Autism spectrum disorder (ASD) is marked by both socio-communicative difficulties and abnormalities in sensory processing. Much of the work on sensory deficits in ASD has focused on tactile sensations and the perceptual aspects of somatosensation, such as encoding of stimulus intensity and location. Although aberrant pain processing has often been noted in clinical observations of patients with ASD, it remains largely uninvestigated. Importantly, the neural mechanism underlying higher order cognitive aspects of pain processing such as pain anticipation also remains unknown. Here we examined both pain perception and anticipation in high-functioning adults with ASD and matched healthy controls (HC) using an anticipatory pain paradigm in combination with functional magnetic resonance imaging (fMRI) and concurrent skin conductance response (SCR) recording. Participants were asked to choose a level of electrical stimulation that would feel moderately painful to them. Compared to HC group, ASD group chose a lower level of stimulation prior to fMRI. However, ASD participants showed greater activation in both rostral and dorsal anterior cingulate cortex during the anticipation of stimulation, but not during stimulation delivery. There was no significant group difference in insular activation during either pain anticipation or perception. However, activity in the left anterior insula correlated with SCR during pain anticipation. Taken together, these results suggest that ASD is marked with aberrantly higher level of sensitivity to upcoming aversive stimuli, which may reflect abnormal attentional orientation to nociceptive signals and a failure in interoceptive inference.

Pain anticipatory phenomena in patients with central poststroke pain: a magnetoencephalography study.

Central poststroke pain (CPSP) is characterized by hemianesthesia associated with unrelenting chronic pain. The final pain experience stems from interactions between sensory, affective, and cognitive components of chronic pain. Hence, managing CPSP will require integrated approaches aimed not only at the sensory but also the affective-cognitive spheres. A better understanding of the brain's processing of pain anticipation is critical for the development of novel therapeutic approaches that target affective-cognitive networks and alleviate pain-related disability. We used magnetoencephalography (MEG) to characterize the neural substrates of pain anticipation in patients suffering from intractable CPSP. Simple visual cues evoked anticipation while patients awaited impending painful (PS), nonpainful (NPS), or no stimulus (NOS) to their nonaffected and affected extremities. MEG responses were studied at gradiometer level using event-related fields analysis and time-frequency oscillatory analysis upon source localization. On the nonaffected side, significantly greater responses were recorded during PS. PS (vs. NPS and NOS) exhibited significant parietal and frontal cortical activations in the beta and gamma bands, respectively, whereas NPS (vs. NOS) displayed greater activation in the orbitofrontal cortex. On the affected extremity, PS (vs. NPS) did not show significantly greater responses. These data suggest that anticipatory phenomena can modulate neural activity when painful stimuli are applied to the nonaffected extremity but not the affected extremity in CPSP patients. This dichotomy may stem from the chronic effects of pain on neural networks leading to habituation or saturation. Future clinically effective therapies will likely be associated with partial normalization of the neurophysiological correlates of pain anticipation.

Patterns of Cerebral Blood Flow Modulation During Painful Stimulation in Fibromyalgia: A Transcranial Doppler Sonography Study.

OBJECTIVE: This study analyzed the temporal dynamics of cerebral blood flow (CBF) modulations, during painful stimulation in fibromyalgia syndrome (FMS), using functional transcranial Doppler sonography. METHOD: Blood flow velocities were recorded bilaterally in the anterior (ACA) and middle (MCA) cerebral arteries of 24 FMS patients and 20 healthy individuals during exposure to painful pressure stimulation. Participants were presented with two stimulation blocks: a) fixed pressure (2.4 kg) and b) stimulation pressure, individually calibrated to produce equal subjective and moderate pain intensity in all participants. RESULTS: A complex pattern of CBF modulations arose, comprising four main components: an anticipatory increase before stimulation onset, an early increase, a transient decrease to baseline or below, and a final increase. Group differences were observed in all components. The anticipatory component only arose in FMS patients, specifically in the ACA. Patients exhibited a greater early CBF increase under the fixed pressure condition, predominantly in the right ACA. A stronger CBF decrease after the early component was observed in patients during the equal pain condition, in the ACA and MCA. Significant associations were found between clinical pain severity and CBF responses in the MCA. CONCLUSIONS: The results demonstrate that acute pain processing is associated with a complex pattern of CBF modulation, where FMS patients exhibited alterations in all phases of the response. The aberrances may be ascribed to psychophysiological phenomena, including central nervous nociceptive sensitization and protective-defensive reflex mechanisms. The anticipatory CBF response in patients may relate to various cognitive, emotional, and behavioral mechanisms involved in pain chronification.

Pain anticipation: an activation likelihood estimation meta-analysis of brain imaging studies.

The anticipation of pain has been investigated in a variety of brain imaging studies. Importantly, today there is no clear overall picture of the areas that are involved in different studies and the exact role of these regions in pain expectation remains especially unexploited. To address this issue, we used activation likelihood estimation meta-analysis to analyze pain anticipation in several neuroimaging studies. A total of 19 functional magnetic resonance imaging were included in the analysis to search for the cortical areas involved in pain anticipation in human experimental models. During anticipation, activated foci were found in the dorsolateral prefrontal, midcingulate and anterior insula cortices, medial and inferior frontal gyri, inferior parietal lobule, middle and superior temporal gyrus, thalamus, and caudate. Deactivated foci were found in the anterior cingulate, superior frontal gyrus, parahippocampal gyrus and in the claustrum. The results of the meta-analytic connectivity analysis provide an overall view of the brain responses triggered by the anticipation of a noxious stimulus. Such a highly distributed perceptual set of self-regulation may prime brain regions to process information where emotion, action and perception as well as their related subcategories play a central role. Not only do these findings provide important information on the neural events when anticipating pain, but also they may give a perspective into nocebo responses, whereby negative expectations may lead to pain worsening.

Anticipation of electric shocks modulates low beta power and event-related fields during memory encoding.

In humans, the temporal and oscillatory dynamics of pain anticipation and its effects on long-term memory are largely unknown. Here, we investigated this open question by using a previously established behavioral paradigm in combination with magnetoencephalography (MEG). Healthy human subjects encoded a series of scene images, which was combined with cues predicting an aversive electric shock with different probabilities (0.2, 0.5 or 0.8). After encoding, memory for the studied images was tested using a remember/know recognition task. Behaviorally, pain anticipation did not modulate recollection-based recognition memory per se, but interacted with the perceived unpleasantness of the electric shock [visual analogue scale rating from 1 (not unpleasant) to 10 (highly unpleasant)]. More precisely, the relationship between pain anticipation and recollection followed an inverted u-shaped function the more unpleasant the shocks were rated by a subject. At the physiological level, this quadratic effect was mimicked in the event-related magnetic fields associated with successful memory formation ('DM-effect') ∼450ms after image onset at left frontal sensors. Importantly, across all subjects, shock anticipation modulated oscillatory power in the low beta frequency range (13-20Hz) in a linear fashion at left temporal sensors. Taken together, our findings indicate that beta oscillations provide a generic mechanism underlying pain anticipation; the effect on subsequent long-term memory, on the other hand, is much more variable and depends on the level of individual pain perception. As such, our findings give new and important insights into how aversive motivational states can drive memory formation.

Body ownership: When feeling and knowing diverge.

Individuals with the peculiar disturbance of 'overcompleteness' experience an intense desire to amputate one of their healthy limbs, describing a sense of disownership for it (Body Integrity Identity Disorder - BIID). This condition is similar to somatoparaphrenia, the acquired delusion that one's own limb belongs to someone else. In ten individuals with BIID, we measured skin conductance response to noxious stimuli, delivered to the accepted and non-accepted limb, touching the body part or simulating the contact (stimuli approach the body without contacting it), hypothesizing that these individuals have responses like somatoparaphrenic patients, who previously showed reduced pain anticipation, when the threat was directed to the disowned limb. We found reduced anticipatory response to stimuli approaching, but not contacting, the unwanted limb. Conversely, stimuli contacting the non-accepted body-part, induced stronger SCR than those contacting the healthy parts, suggesting that feeling of ownership is critically related to a proper processing of incoming threats.

A magnetoencephalography study of visual processing of pain anticipation.

Anticipating pain is important for avoiding injury; however, in chronic pain patients, anticipatory behavior can become maladaptive, leading to sensitization and limiting function. Knowledge of networks involved in pain anticipation and conditioning over time could help devise novel, better-targeted therapies. With the use of magnetoencephalography, we evaluated in 10 healthy subjects the neural processing of pain anticipation. Anticipatory cortical activity elicited by consecutive visual cues that signified imminent painful stimulus was compared with cues signifying nonpainful and no stimulus. We found that the neural processing of visually evoked pain anticipation involves the primary visual cortex along with cingulate and frontal regions. Visual cortex could quickly and independently encode and discriminate between visual cues associated with pain anticipation and no pain during preconscious phases following object presentation. When evaluating the effect of task repetition on participating cortical areas, we found that activity of prefrontal and cingulate regions was mostly prominent early on when subjects were still naive to a cue's contextual meaning. Visual cortical activity was significant throughout later phases. Although visual cortex may precisely and time efficiently decode cues anticipating pain or no pain, prefrontal areas establish the context associated with each cue. These findings have important implications toward processes involved in pain anticipation and maladaptive pain conditioning.

Pain anticipation is a new behavioural sign of minimally conscious state.

Probing cognition and consciousness in the absence of functional communication remains an extremely challenging task. In this perspective, we imagined a basic clinical procedure to explore pain anticipation at bedside. In a series of 61 patients with a disorder of consciousness, we tested the existence of a nociceptive anticipation response by pairing a somaesthetic stimulation with a noxious stimulation. We then explored how nociceptive anticipation response correlated with (i) clinical status inferred from Coma Recovery Scale-Revised scoring, (ii) with an EEG signature of stimulus anticipation-the contingent negative variation-and (iii) how nociceptive anticipation response could predict consciousness outcome at 6 months. Proportion of nociceptive anticipation response differed significantly according to the state of consciousness: nociceptive anticipation response was present in 5 of 5 emerging from minimally conscious state patients (100%), in 10 of 11 minimally conscious state plus patients (91%), but only in 8 of 17 minimally conscious state minus patients (47%), and only in 1 of 24 vegetative state/unresponsive wakefulness syndrome patients (4%) (χ 2  P < 0.0001). Nociceptive anticipation response correlated with the presence of a contingent negative variation, suggesting that patients with nociceptive anticipation response were more prone to actively expect and anticipate auditory stimuli (Fisher's exact test P = 0.05). However, nociceptive anticipation response presence did not predict consciousness recovery. Nociceptive anticipation response appears as a new additional behavioural sign that can be used to differentiate minimally conscious state from vegetative state/unresponsive wakefulness syndrome patients. As most behavioural signs of minimally conscious state, the nociceptive anticipation response seems to reveal the existence of a cortically mediated state that does not necessarily reflect residual conscious processing.

Dysfunctional Activation of the Dorsolateral Prefrontal Cortex During Pain Anticipation Is Associated With Altered Subsequent Pain Experience in Fibromyalgia Patients.

The ability to accurately predict pain is an adaptive feature in healthy individuals. However, in chronic pain, this mechanism may be selectively impaired and can lead to increased anxiety and excessive avoidance behavior. Recently, we reported the first data demonstrating brain activation in fibromyalgia (FM) patients during conditioned pain responses, in which FM patients revealed a tendency to form new pain-related associations rather than extinguishing irrelevant ones. The aim of the present study was to extend our previous analysis, to elucidate potential neural divergences between subjects with FM (n = 65) and healthy controls (HCs) (n = 33) during anticipatory information (ie, prior to painful stimulus onset). Using functional magnetic resonance imaging (fMRI), the current analyses include 1) a congruently cued paradigm of low and high pain predictive cues, followed by 2) an incongruently cued paradigm where low and high pain predictive cues were followed by an identical mid-intensity painful pressure. During incongruently cued high-pain associations, FM exhibited reduced left dorsolateral prefrontal cortex (dlPFC) activation compared to HCs, which was followed by an altered subsequent pain experience in FM, as patients continued to rate the following painful stimuli as high, even though the pressure had been lowered. During congruently cued low pain anticipation, FM exhibited decreased right dlPFC activation compared to HCs, as well as decreased brain connectivity between brain regions implicated in cognitive modulation of pain (dlPFC) and nociceptive processing (primary somatosensory cortex/postcentral gyrus [S1] and supplementary motor area [SMA]/midcingulate cortex [MCC]). These results may reflect an important feature of validating low pain expectations in HCs and help elucidate behavioral reports of impaired safety processing in FM patients. PERSPECTIVE: FM exhibited a stronger conditioned pain response for high-pain associations, which was associated with reduced dlPFC activation during the incongruent trial. During (congruent and incongruent) low pain associations, FM dlPFC brain activation remained indifferent. Imbalances in threat and safety pain perception may be an important target for psychotherapeutic interventions.

How does feeling pain look like in depression: A review of functional neuroimaging studies.

INTRODUCTION: Major Depression Disorder (MDD) and pain appear to be reciprocal risk factors and sharing common neuroanatomical pathways and biological substrates. However, the role of MDD on pain processing remains still unclear. Therefore, this review aims to focus on the effect of depression on pain anticipation, and perception, before and after treatment, through functional magnetic resonance imaging (fMRI). METHODS: A bibliographic search was conducted on PubMed, Scopus and Web of Science, looking for fMRI studies exploring pain processing in MDD patients. RESULTS: Amongst the 602 studies retrieved, 12 met the inclusion criteria. In terms of pain perception, studies evidenced that MDD patients generally presented increased activation in brain regions within the prefrontal cortex, insula and in the limbic system (such as amygdala, hippocampus) and occipital cortex. The studies investigating the effect of antidepressant treatment evidenced a reduced activation in areas such as insula, anterior cingulate, and prefrontal cortices. In terms of pain anticipation, contrasting results were evidenced in MDD patients, which presented both increased and decreased activity in the prefrontal cortex, the insula and the temporal lobe, alongside with increased activity in the anterior cingulate cortex, the frontal gyrus and occipital lobes. LIMITATIONS: The small number of included studies, the heterogeneous approaches of the studies might limit the conclusions of this review. CONCLUSIONS: Acute pain processing in MDD patients seems to involve numerous and different brain areas. However, more specific fMRI studies with a more homogeneous population and rigorous approach should be conducted to better highlight the effect of depression on pain processing.

Pavlovian threat learning shapes the kinematics of action.

Prompt response to environmental threats is critical to survival. Previous research has revealed mechanisms underlying threat-conditioned physiological responses, but little is known about how threats shape action. Here we tested if threat learning shapes the kinematics of reaching in human adults. In two different experiments conducted on independent samples of participants, after Pavlovian threat learning, in which a stimulus anticipated the delivery of an aversive shock, whereas another did not, the peak velocity and acceleration of reaching increased for the shocked-paired stimulus, relative to the unpaired one. These kinematic changes appeared as a direct consequence of learning, emerging even in absence of an actual threat to body integrity, as no shock occurred during reaching. Additionally, they correlated with the strength of sympathetic response during threat learning, establishing a direct relationship between previous learning and subsequent changes in action. The increase in velocity and acceleration of action following threat learning may be adaptive to facilitate the implementation of defensive responses. Enhanced action invigoration may be maladaptive, however, when defensive responses are inappropriately enacted in safe contexts, as exemplified in a number of anxiety-related disorders.

Pain and Avoidance during and after Endodontic Therapy: The Role of Pain Anticipation and Self-Efficacy.

BACKGROUND: Pain anticipation has been identified as a predictor of pain and avoidance with respect to endodontic therapy. Self-efficacy is also key to the development and maintenance of health behaviors and achieve patient adherence to treatment. However, the role of self-efficacy has not been studied yet in endodontic treatment. METHODS: This study was conducted on 101 patients who needed root canal therapy. They had to fill a questionnaire before treatment registered pain anticipation and self-efficacy; during and after treatment were registered pain intensity and avoidance. RESULTS: Pain anticipation explained pain during (Beta = 0.51, t = 5.82, p ≤ 0.001, [0.34, 0.69]) and after treatment (Beta = 0.38, t = 4.35, p ≤ 0.001, [0.21, 0.55]). Self-efficacy did not have an influence in pain values. Pain anticipation explained avoidance during (Beta = 0.51, t = 3.60, p ≤ 0.001, [0.23, 0.80]) and after treatment (Beta = 0.62, t = 4.29, p ≤ 0.001, [0.33, 0.91]). Self-efficacy had a significant role in avoidance during treatment (Beta = 0.12, t = 2.19, p ≤ 0.03, [0.01, 0.23]) with a strong moderation relationship between pain anticipation and avoidance when self-efficacy was medium (Beta = 0.44, t = 3.24, p = 0.002, [0.17, 0.72]) or high (Beta = 0.84, t = 3.5, p ≤ 0.001, [0.37, 1.33]). Self-efficacy was not significant respect to avoidance after treatment. CONCLUSIONS: Self-efficacy is an important variable in endodontic therapy due to their moderating effect between pain anticipation and avoidance behavior during the procedure. It is necessary to improve the results of root canal therapy and reduce patient's avoidance in order to take into account this variable.

Psychophysiological correlates of pain resilience in anticipating, experiencing, and recovering from pain.

Although researchers have documented behavioral and brain structure correlates of pain resilience, associated physiological responses have received little consideration. In this study, we assessed psychophysiological differences between high (HPR), moderate (MPR), and low (LPR) pain resilience subgroups during anticipation, experiencing, and recovery from laboratory pain. In an initial pain anticipation task, participants (79 women, 32 man) viewed visual cues to signal possible mild or intense shocks prior to receiving these shocks. Subsequently, in a pain recovery task, participants received uncued mild and intense shocks. Subjective appraisals were assessed during each task in tandem with continuous recording of skin conductance level (SCL), heart rate variability (HRV), and corrugator electromyography (cEMG). On physiological indexes, HPR subgroup members displayed significantly lower SCL than MPR and LPR subgroups did during anticipation and experiencing of pain while no resilience group effects were found for HRV or cEMG. During pain recovery, HPR and LPR subgroups displayed weaker SCL than the MPR subgroup did in the immediate aftermath of shock. However, HPR members continued to display lower SCL than other groups did over an extended recovery period. On self-report measures, the LPR subgroup reported higher levels of anticipatory anxiety and expected pain than HPR and MPR subgroups did during the pain anticipation task. Together, results suggested higher pain resilience is characterized, in part, by comparatively reduced SCL during the course of anticipating, experiencing and recovering from painful shock.

Cognitive reappraisal is not always successful during pain anticipation: Stimulus-focused and goal-based reappraisal effects on self-reports and peripheral psychophysiology.

The present study aims at comparing the effects of two subtypes of cognitive reappraisal (i.e., stimulus-focused vs. goal-based reappraisal) to reduce anticipatory anxiety of pain. Affective ratings, startle reflex, and autonomic measures (electrodermal and heart rate changes) were used as a measure of emotion regulation success. A total of 86 undergraduate students completed an anticipatory task in which they had to regulate their negative emotions or react naturally when faced with the possibility of receiving a painful thermal stimulus. Participants were randomly assigned to two experimental groups to compare the stimulus-focused and goal-based strategies explored here. Our results revealed enhanced self-reported anxiety, electrodermal activity and eyeblink response when participants tried to voluntarily down-regulate their negative emotions, compared to the control instruction. Differences between both cognitive reappraisal groups were not found. These unexpected findings suggest that brief reappraisal instructions may not necessarily be favorable for regulating emotions during anticipation of aversive events. Moreover, these results are further explained in terms of the pain expectation, the painful stimuli modality, and emotion regulation instructions.

Pain Anticipation and Nocebo-Related Responses: A Descriptive Mini-Review of Functional Neuroimaging Studies in Normal Subjects and Precious Hints on Pain Processing in the Context of Neurodegenerative Disorders.

The exacerbation of a clinical condition or the occurrence of negative symptoms after an inert substance dispensation or a sham treatment is known as "nocebo effect." Nocebo is the psychobiological effect due to the negative psychosocial context that accompanies a therapy, and it is a direct consequence of negative expectations by the patients and their own personal characteristics. Although the clinical relevance of the phenomenon is now recognized, a small number of studies have tried to ascertain its neural underpinnings (that it means nocebo responses). Moreover, there is no consensus on the brain networks involved in nocebo processes in humans. In particular, nocebo hyperalgesia has attracted almost no research attention. We conducted a mini-review on the few experimental pain functional magnetic resonance imaging (fMRI) studies of nocebo responses to discuss how negative expectancies and conditioning effects engage brain networks to modulate pain experiences. Moreover, we present possible clinical implications considering Alzheimer's disease and behavioral frontotemporal dementia, in which the existence of a hypothetically disrupted neurocognitive anticipatory network-secondary to an endogenous pain modulatory system damage-may be responsible for pain processing alterations.

Brain Mechanisms of Anticipated Painful Movements and Their Modulation by Manual Therapy in Chronic Low Back Pain.

Heightened anticipation and fear of movement-related pain has been linked to detrimental fear-avoidance behavior in chronic low back pain (cLBP). Spinal manipulative therapy (SMT) has been proposed to work partly by exposing patients to nonharmful but forceful mobilization of the painful joint, thereby disrupting the relationship among pain anticipation, fear, and movement. Here, we investigated the brain processes underpinning pain anticipation and fear of movement in cLBP, and their modulation by SMT, using functional magnetic resonance imaging. Fifteen cLBP patients and 16 healthy control (HC) subjects were scanned while observing and rating video clips depicting back-straining or neutral physical exercises, which they knew they would have to perform at the end of the visit. This task was repeated after a single session of spinal manipulation (cLBP and HC group) or mobilization (cLBP group only), in separate visits. Compared with HC subjects, cLBP patients reported higher expected pain and fear of performing the observed exercises. These ratings, along with clinical pain, were reduced by SMT. Moreover, cLBP, relative to HC subjects, demonstrated higher blood oxygen level-dependent signal in brain circuitry that has previously been implicated in salience, social cognition, and mentalizing, while observing back straining compared with neutral exercises. The engagement of this circuitry was reduced after SMT, and especially the spinal manipulation session, proportionally to the magnitude of SMT-induced reduction in anticipated pain and fear. This study sheds light on the brain processing of anticipated pain and fear of back-straining movement in cLBP, and suggests that SMT may reduce cognitive and affective-motivational aspects of fear-avoidance behavior, along with corresponding brain processes. PERSPECTIVE: This study of cLBP patients investigated how SMT affects clinical pain, expected pain, and fear of physical exercises. The results indicate that one of the mechanisms of SMT may be to reduce pain expectancy, fear of movement, and associated brain responses.