Anticipation Of Pain Research Articles

The effect of anxiety sensitivity on psychological and biological variables during the cold pressor test.

We examined the relationship between anxiety sensitivity (AS) and autonomic nervous system responses (ANS) during the cold pressor test (CPT). Seventy-four university students participated and were divided into low-AS (M=9.06, SD=3.97) and high-AS groups (M=28.68, SD=6.63) based on AS Index scores (n's=36 and 38, respectively). The study included three phases: Rest, CPT, and Recovery. We measured the psychological variables (fear of pain and subjective pain) at pre- and post-CPT. ANS response data were collected during each phase. Fear of pain was experienced more strongly in the high-AS group (M=4.74, SD=3.25) relative to the low-AS group (M=2.72, SD=2.31), and subjective pain was also stronger in the high-AS group (M=3.08, SD=1.91) relative to the low-AS group (M=2.47, SD=1.00) in post-CPT. While parasympathetic nervous system (PNS) responses did not differ between the two groups during the CPT, the high AS-group demonstrated lower PNS activity during the Recovery phase. The high-AS group reported significantly more anticipatory fear and pain prior to the CPT, which appeared to aggravate subjective pain experiences. Furthermore, for individuals with anxiety sensitivity, ANS reactivity may be the mechanism underlying the relationship between negative affect and subjective pain.

Influence Of Physical Activity And Sedentary Behavior On Anticipation-related Pain Sensitivity In Gulf War Veterans With Chronic Muscle Pain

Exercise can alter pain sensitivity among Gulf War Veterans with chronic muscle pain (CMP). Anticipation of a painful experience can influence perceptual and neural responses to non-painful thermal stimuli among Fibromyalgia patients and this may extend to other patient groups with CMP. However, the association between physical activity or sedentary behavior and anticipation-related pain sensitivity has not been adequately studied. PURPOSE: To determine if (i) anticipation of pain influenced perceptual and neural responses to thermal stimuli among Veterans with CMP and (ii) anticipation-related pain sensitivity was associated with physical activity or sedentary behavior. METHODS: Gulf War Veterans with (n=29; 46±6.5 years) and without (n=29; 45±6.7 years) CMP were randomly assigned to conditions in which they were told that they would receive a painful or non-painful heat stimulus. Following one week of physical activity monitoring (ActiGraph GT3X), functional MRI responses to a 20-second warm stimulus (40C) applied to the left palm were measured on a 3T MRI scanner (GE MR750). Participants were then asked to provide ratings of pain intensity and unpleasantness following thermal stimulus administration. RESULTS: Factorial ANOVA with group and condition as between-subjects factors revealed significantly higher pain intensity (p =.003; d =.85) and unpleasantness (p =.006; d=0.76) ratings in the pain anticipation condition. A main effect for group and condition by group interaction was not found. Analyses of fMRI responses showed significantly different lateral postcentral gyrus activation in the pain anticipation condition. Linear regression analyses on Veterans in the pain anticipation condition showed that physical activity (e.g., moderate-vigorous physical activity) and sedentary behavior (e.g., average sedentary bouts of 30 or 60 minutes) did not significantly predict perception of pain intensity or unpleasantness. CONCLUSION: Pain anticipation influences perceptual and neural responses to non-painful stimuli among Gulf War Veterans with or without CMP; however, physical activity or sedentary behavior may not be related to anticipation-related pain sensitivity in this population. Supported by Dept. of Veterans Affairs grant: 561-00436

Fear of pain changes movement: Motor behaviour following the acquisition of pain-related fear.

According to current fear-avoidance models, changes in motor behaviour (e.g. avoidance) are a key component in the development and maintenance of chronic pain complaints. Yet, experimental research assessing actual behavioural changes following painful events is relatively sparse. This study investigated the effects of pain anticipation on changes in motor behaviour using a fear conditioning paradigm and robot-generated standardized movement trajectories of the upper extremities. Pain-free participants (N=20) performed clockwise and counterclockwise fixed, circular movements with a robotic arm without receiving visual feedback. During fear acquisition, moving in one direction (CS+) was paired with a painful stimulus (pain-US) whereas moving in the other direction (CS-) was not. During the subsequent extinction phase, the pain-US was omitted. We assessed self-reported pain-related fear and urge to avoid the movement, as well as several behavioural measures: Velocity, acceleration, exerted force and force direction. Movements that were paired with pain were associated with increased self-reported pain-related fear and urge to avoid. Moreover, movements that were associated with pain were performed faster, more forcefully and more accurately than movements that were not associated with pain. All these differences diminished during the extinction phase. The present study demonstrates the utility of robot-generated force feedback in the study of pain-related fear and associated changes in motor behaviour. Fear of pain changes movement: Movements associated with pain are performed faster, with more force and higher accuracy than movements that are not associated with pain. These changes can inform us how fear of pain translates into avoidance and escape behaviour, two important constructs in the maintenance of chronic pain.

Altered neural responses to heat pain in drug-naive patients with Parkinson disease.

Pain is a frequent but still neglected nonmotor symptom of Parkinson disease (PD). However, neural mechanisms underlying pain in PD are poorly understood. Here, we explored whether the high prevalence of pain in PD might be related to dysfunctional descending pain control. Using functional magnetic resonance imaging we explored neural responses during the anticipation and processing of heat pain in 21 PD patients (Hoehn and Yahr I-III) and 23 healthy controls (HC). Parkinson disease patients were naive to dopaminergic medication to avoid confounding drug effects. Fifteen heat pain stimuli were applied to the participants' forearm. Intensity and unpleasantness ratings were provided for each stimulus. Subjective pain perception was comparable for PD patients and HC. Neural processing, however, differed between groups: PD patients showed lower activity in several descending pain modulation regions (dorsal anterior cingulate cortex [dACC], subgenual anterior cingulate cortex, and dorsolateral prefrontal cortex [DLPFC]) and lower functional connectivity between dACC and DLPFC during pain anticipation. Parkinson disease symptom severity was negatively correlated with dACC-DLPFC connectivity indicating impaired functional coupling of pain modulatory regions with disease progression. During pain perception PD patients showed higher midcingulate cortex activity compared with HC, which also scaled with PD severity. Interestingly, dACC-DLPFC connectivity during pain anticipation was negatively associated with midcingulate cortex activity during the receipt of pain in PD patients. This study indicates altered neural processing during the anticipation and receipt of experimental pain in drug-naive PD patients. It provides first evidence for a progressive decline in descending pain modulation in PD, which might be related to the high prevalence of pain in later stages of PD.

Oxytocin Signaling in Pain: Cellular, Circuit, System, and Behavioral Levels.

Originally confined to the initiation of parturition and milk ejection after birth, the hypothalamic nonapeptide oxytocin (OT) is now recognized as a critical determinant of social behavior and emotional processing. It accounts for the modulation of sensory processing and pain perception as OT displays a potent analgesic effect mediated by OT receptors (OTRs) expressed in the peripheral and central nervous systems. In our chapter, we will first systemically analyze known efferent and afferent OT neuron projections, which form the anatomical basis for OT modulation of somatosensory and pain processing. Next, we will focus on the synergy of distinct types of OT neurons (e.g., magno- and parvocellular OT neurons) which efficiently control acute inflammatory pain perception. Finally, we will describe how OT signaling mechanisms in the spinal cord control nociception, as well as how OT is able to modulate emotional pain processing within the central amygdala. In the conclusions at the end of the chapter, we will formulate perspectives in the study of OT effects on pain anticipation and pain memory, as well as propose some reasons for the application of exogenous OT for the treatment of certain types of pain in human patients.

The relationship between Dispositional Optimism, Pain Experience and Pain anticipation

Background: Dispositional optimism is an individual difference variable that reflects the extent to which people hold generalized favorable expectancies for their future. It has been suggested to be a protective factor for pain. This study investigates the relationship between dispositional optimism and pain experience, and what role pain anticipation plays in this relationship. A positive impact of dispositional optimism on pain experience is expected. Furthermore, it is expected that pain anticipation has a negative association with both dispositional optimism and pain experience, but also may be a mediator in the relationship between dispositional optimism and pain experience. Methods: The study has a cross-sectional design and was performed on 36 bachelor students of Maastricht University. The study population has an age ranged from 18 to 24 years old (mean= 20,75 years; SD= 1,84). Experimental pain was induced by means of the Medoc Pathway Advanced Thermal Stimulator (ATS; MEDOC). Pain experience was separated in pain threshold and pain tolerance measurements. Dispositional optimism was measured with the Life Orientation Test-Revised (LOT-R). Pain anticipation was separated in three items; expected pain, expected unpleasantness, and expected fear, which were measured on a visual analogue scale before the start of the pain stimulus. Results: For pain anticipation and pain experience only expected pain shows a significant correlation with pain experience’s measurement pain tolerance. There is no significant link between dispositional optimism and pain experience; therefore, pain anticipation is not tested as a mediator. In the correlation between pain anticipation and dispositional optimism, the link between expected pain and the total LOT-R score is significant. Furthermore, the links between expected pain, expected unpleasantness and expected fear and the negative subscale of the LOT-R score are significant. Conclusion: This study did not confirm the suggested relationship between dispositional optimism and pain experience, although it does confirm a significant correlation between pain anticipation and dispositional optimism.

Regional Perfusion in Sickle Cell Subjects and Normal Controls Is a Physiological Biomarker of Mental Stress and Fear of Pain

Introduction: Sickle cell disease (SCD) is a genetic disorder characterized by sudden onset of painful vaso-occlusive episodes (VOC) which can be triggered by stress as reported by sickle cell patients. The exact mechanism of VOC origin is not well understood; however, it could result as a progression of microvascular blockade with rigid sickled red blood cells (RBC). Anything that decreases regional blood flow (RBF) will increase the transit time that it takes the RBC to escape the microvasculature before it gets rigid and entrapped, thus increasing the chances of vaso-occlusion that may progress to VOC. The RBF is controlled by the autonomic nervous system (ANS) which is modulated by stress, and as we have previously shown, SCD patients have augmented autonomic mediated vasoconstriction response (VCR) to sigh and pain. Our studies showed significant VCR when subjects were told they were about to experience pain, suggesting that VCR might be the physiologic link between common VOC triggers like stress and sickled RBC retention in the microvasculature.Objectives: To study the effect of mental stress on autonomic parameters peripheral blood flow (PBF) and heart rate variability (HRV) in SCD.Methods: 19 SCD and 16 control (healthy and sickle cell trait) subjects were studied. Two standard mental stress tasks with graded levels of difficulty (N-back test and Stroop test) were presented to subjects using E-prime (Psychological software). Subjects were also exposed to a novel pain anticipation task, previously shown to induce VCR.PBF was measured using photo-plethysmography (PPG) on the left thumb. Reduction in PPG amplitude indicates vasoconstriction. Cardiac beat-to-beat variability (R-to-R interval;RRI) was extracted from electrocardiogram. ANS balance was derived from the following spectral indices of the RRI: high frequency power (HFP) ≈ parasympathetic activity, low frequency power (LFP), and the low/high ratio (LFP/HFP) representing sympathovagal balance.Average changes in PBF and HRV from the baseline were taken as the responses to the mental tasks.Results: There was a significant decrease in mean PBF, RRI and HFP during all the mental stressors (N-back test, Stroop test and pain fear) compared to the baseline (p<0.01). Based on task accuracy scores, there was clear difference in sublevels of task difficulty (p<0.0001). While PBF decreased during all the sublevels of N-back and Stroop compared to baseline (p<0.01), there was no PBF difference between the task sublevels. However, when subjects were told that they were about to experience severe pain from heat applied to their arm in a sham pain instruction that was given after N-back and Stroop, there was a significant decrease in PBF compared to baseline (p<0.001) and compared to the response during N-back (p<0.01). The parasympathetic withdrawal in response to mental tasks and fear of pain followed a similar pattern.Conclusions: Graded mental stress and fear of pain causes significant decrease in regional blood flow and parasympathetic withdrawal in SCD subjects and normal controls. The vasoconstriction response to "fear of pain" was significantly greater than the VRC caused by N-back and to a lesser extent in Stroop. The pattern of responses were not significantly different between SCD and controls however the consequences of decreased blood flow could be quite different because of the resulted entrapment of sickle cells in the microvasculature. This could explain how stress may play a role in the initiation of VOC in SCD by enhancing ANS mediated vasoconstriction, prolonging microvascular transit time and increasing the likelihood of vaso-occlusion.The 1st signal is mental tasks event marker, 2nd signal is photo-plethysmography (PPG) and the 3rd signal is heart rate variability derived from the electrocardiogram signal. [Display omitted] [Display omitted] DisclosuresWood:Celgene: Consultancy; AMAG: Consultancy; Ionis Pharmaceuticals: Consultancy; Vifor: Consultancy; Ionis Pharmaceuticals: Consultancy; Biomed Informatics: Consultancy; Vifor: Consultancy; World Care Clinical: Consultancy; World Care Clinical: Consultancy; Celgene: Consultancy; AMAG: Consultancy; Apopharma: Consultancy; Apopharma: Consultancy; Biomed Informatics: Consultancy.

Direct Interactive Public Education by Breast Radiologists About Screening Mammography: Impact on Anxiety and Empowerment

PurposeAnxiety has been called a “harm” of screening mammography. The authors provided direct, interactive education to lay audiences and measured these sessions’ impact on anxiety and any increased understanding of breast cancer screening. MethodsAcademic breast radiologist provided seven 1-hour sessions of structured lectures and question-and-answer periods. Lay language and radiologic images were used to discuss disease background, screening guidelines, and areas of debate. One hundred seventeen participants (mean age, 45 ± 15 years) completed voluntary, anonymous, institutional review board-approved pre and postsession questionnaires relaying their attitudes regarding screening and the impact of the sessions. Results are summarized descriptively. ResultsMean reported anxiety regarding screening (on a scale ranging from 1-5; 1 = no anxiety) was 2.5 ± 1.3. Anxiety was attributed to unknown results (56.4%), anticipation of pain (21.8%), known risk factors (14.5%), general uncertainty (12.7%), waiting for results (9.1%), possibility of more procedures (3.6%), and personal breast cancer history (3.6%). Ninety-seven percent reported that immediate results would lower anxiety (78% of those women indicated a 75%-100% decrease in anxiety); 93% reported that radiologist consultation with images would lower anxiety (75.6% indicated a 75%-100% decrease in anxiety). After the lecture, women reported (on a scale ranging from 1-5) increased understanding of the topic (4.7 ± 0.6), encouragement to screen (4.6 ± 0.7), and reduced anxiety (4.0 ± 1.1). Ninety-seven percent to 100% provided correct responses to these questions: rationale for screening in the absence of family history, recall does not equate to cancer diagnosis, benefit of prior films, and continued importance of physical examination. ConclusionAttendees of radiologist-provided direct public lectures reported decreased anxiety and improved knowledge regarding screening mammography. The resultant reduced anxiety (“harm”) and educational empowerment help enable informed decision making and may promote screening attendance.

Pilot Study of Functional Magnetic Resonance Imaging Responses to Somatic Pain Stimuli in Youth With Functional and Inflammatory Gastrointestinal Disease.

Brain-gut axis signaling modifies gastrointestinal symptomatology. Altered neural processing of intestinal pain signals involves interoceptive brain regions in adults with functional and inflammatory gastrointestinal disorders. Although these disorders frequently present in childhood, there are no published studies in youth. We determined whether neural processing of somatic pain stimuli differs in adolescents and young adults (AYA) with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), as compared to healthy controls (HC). IBS and IBD AYA (16-20 years) underwent anticipated and thermal pain stimuli of low and high intensity on their forearm and simultaneous blood oxygen level-dependent functional magnetic resonance imaging. Data from adult HC were used for comparison. Subjects answered surveys evaluating alexithymia, anxiety, depression, and pain catastrophizing. Group data were compared using linear mixed effects and analysis of variance. Study groups were similar by sex but not age. Significant group by pain condition interactions were observed in interoceptive brain regions during pain anticipation, and within perceptual brain regions during perceived pain. Higher activation within interoceptive brain regions during anticipated pain was observed in IBS compared with IBD and HC subjects. IBD patients demonstrated increased activation in perceptual brain regions during experienced pain as compared to IBS and HC. IBS and IBD AYA demonstrate altered neural processing of somatic pain compared with each other and with HC. Our results suggest that neuromodulatory interventions targeting interoceptive brain circuits in IBS and perceptual brain regions in IBD may be effective.

Neural Activation during Anticipation of Near Pain-Threshold Stimulation among the Pain-Fearful.

Fear of pain (FOP) can increase risk for chronic pain and disability but little is known about corresponding neural responses in anticipation of potential pain. In this study, more (10 women, 6 men) and less (7 women, 6 men) pain-fearful groups underwent whole-brain functional magnetic resonance imaging (fMRI) during anticipation of near pain-threshold stimulation. Groups did not differ in the proportion of stimuli judged to be painful but pain-fearful participants reported significantly more state fear prior to stimulus exposure. Within the entire sample, stronger activation was found in several pain perception regions (e.g., bilateral insula, midcingulate cortex (MCC), thalamus, superior frontal gyrus) and visual areas linked to decoding stimulus valences (inferior orbital cortex) during anticipation of “painful” stimuli. Between groups and correlation analyses indicated pain-fearful participants experienced comparatively more activity in regions implicated in evaluating potential threats and processing negative emotions during anticipation (i.e., MCC, mid occipital cortex, superior temporal pole), though group differences were not apparent in most so-called “pain matrix” regions. In sum, trait- and task-based FOP is associated with enhanced responsiveness in regions involved in threat processing and negative affect during anticipation of potentially painful stimulation.

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.

Brain responses to uncertainty about upcoming rectal discomfort in quiescent Crohn's disease - a fMRI study.

Patients with Crohn's disease (CD) in remission are exposed to chronic psychological distress, due to the constant risk of relapse. This permanent situation of anticipation and uncertainty can lead to anxiety, which may, in turn, trigger relapse. We aimed to investigate the effects of uncertainty on behavioral and brain responses to anticipation of visceral discomfort in quiescent CD patients. Barostat-controlled rectal distensions were preceded by cued uncertain or certain anticipation in nine CD patients and nine matched healthy volunteers. Brain responses obtained before distension across the different anticipation conditions in regions of interest (ROI) involved in (anticipation of) pain were measured using functional magnetic resonance imaging and compared between CD and controls. The association between anxiety-related psychological variables and cerebral anticipatory activity was tested. During uncertainty, CD patients had significantly stronger activations than controls in the cingulate cortex, insula, amygdala, and thalamus with trends in the hippocampus, prefrontal, and secondary somatosensory cortex. In patients, brain responses to uncertainty in the majority of ROI correlated positively with gastrointestinal symptom-specific anxiety, trait-anxiety, and intolerance of uncertainty. In a context of uncertainty regarding occurrence of uncomfortable visceral sensations, CD is associated with excessive reactivity in brain regions known to be involved in sensory, cognitive and emotional aspects of pain processing and modulation, and threat appraisal. Our findings contribute to a better understanding of the role of emotional and cognitive processes in CD. This may, in turn, lead to the development of new (psycho)therapeutic approaches for management of symptoms and related anxiety.

Altered Neural Activity Associated with Mindfulness during Nociception: A Systematic Review of Functional MRI.

Objective: To assess the neural activity associated with mindfulness-based alterations of pain perception. Methods: The Cochrane Central, EMBASE, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched on 2 February 2016. Titles, abstracts, and full-text articles were independently screened by two reviewers. Data were independently extracted from records that included topics of functional neuroimaging, pain, and mindfulness interventions. Results: The literature search produced 946 total records, of which five met the inclusion criteria. Records reported pain in terms of anticipation (n = 2), unpleasantness (n = 5), and intensity (n = 5), and how mindfulness conditions altered the neural activity during noxious stimulation accordingly. Conclusions: Although the studies were inconsistent in relating pain components to neural activity, in general, mindfulness was able to reduce pain anticipation and unpleasantness ratings, as well as alter the corresponding neural activity. The major neural underpinnings of mindfulness-based pain reduction consisted of altered activity in the anterior cingulate cortex, insula, and dorsolateral prefrontal cortex.

Anticipation of thermal pain in diverticular disease.

BackgroundThe relative importance of peripheral nerve injury or central pain processing in painful diverticular disease (DD) is unclear. Functional magnetic resonance imaging (fMRI) has demonstrated that dysfunctional central pain processing predominates in irritable bowel syndrome (IBS). This study aims to identify anticipatory changes in symptomatic DD (SDD) compared to asymptomatic DD (ADD) and IBS patients.MethodsGastrointestinal symptoms and somatization were evaluated via the Patient Health Question‐12 Somatic Symptom and the SDD group divided into low (≤6 [LSDD]) and high (≥7 [HSDD]) somatization. Cued painful cutaneous thermal stimuli were delivered to the left hand and foot during fMRI. Fixed effect group analysis of the ‘cued’ anticipatory phase was performed.Key ResultsWithin the right posterior insula, greater deactivation was found in the ADD compared to other groups. In emotion processing centers, anterior and middle insula, greater activation was identified in all patient compared to the ADD group, and in LSDD compared to IBS and HSDD groups. In comparison, amygdala deactivation was greater in ADD than the IBS and HSDD groups, and in LSDD vs HSDD groups. Descending nociceptive control centers, such as the superior medial frontal and orbitofrontal cortex, also showed greater deactivation in the ADD and LSDD compared to the HSDD and IBS groups.Conclusions & InferencesThe HSDD group have altered anticipatory responses to thermal pain, similar to IBS group. The LSDD are similar to ADD group. This suggests underlying differences in pain pathophysiology, and the need for individualized treatment strategies to target the cause of their chronic pain.

Using temporal order judgments to investigate attention bias toward pain and threat-related information. Methodological and theoretical issues.

Recently, Vanden Bulcke, Crombez, Durnez, and Van Damme (2015) investigated whether the attentional prioritization of a specific location due to the anticipation of pain is modality specific or multisensory. They used a temporal order judgment task in which participants judged the order of either two tactile or two visual stimuli, one presented on each hand. Additionally, participants either expected the occurrence of a painful stimulus on one hand or the absence of any pain. Results showed that participants' judgments were biased to the advantage of the stimuli, tactile or visual, presented at the location where pain was expected. The authors concluded that the anticipation of pain leads to a multisensory prioritization of information presented at the threatened spatial location. Here, we would like to question their conclusion in terms of a genuine attentional modulation of multisensory nature, based on methodological and theoretical grounds.

From Pavlov to pain: How predictability affects the anticipation and processing of visceral pain in a fear conditioning paradigm

Conditioned pain-related fear may contribute to hyperalgesia and central sensitization, but this has not been tested for interoceptive, visceral pain. The underlying ability to accurately predict pain is based on predictive cue properties and may alter the sensory processing and cognitive–emotional modulation of pain thus exacerbating the subjective pain experience. In this functional magnetic resonance imaging study using painful rectal distensions as unconditioned stimuli (US), we addressed changes in the neural processing of pain during the acquisition of pain-related fear and subsequently tested if conditioned stimuli (CS) contribute to hyperalgesia and increased neural responses in pain-encoding regions. N=49 healthy volunteers were assigned to one of two groups and underwent 3T fMRI during acquisition of either differential fear conditioning (predictable) or non-contingent presentation of CS and US (unpredictable). During a subsequent test phase, pain stimuli signaled randomly by the CSs were delivered. For the acquisition, results confirmed differential conditioning in the predictable but not the unpredictable group. With regard to activation in response to painful stimuli, the unpredictable compared to the predictable group revealed greater activation in pain-encoding (somatosensory cortex, insula) and pain-modulatory (prefrontal and cingulate cortices, periaqueductal grey, parahippocampus) regions. In the test phase, no evidence of hyperalgesia or central sensitization was found, but the predictable group demonstrated enhanced caudate nucleus activation in response to CS−-signaled pain. These findings support that during fear conditioning, the ability to predict pain affects neural processing of visceral pain and alters the associative learning processes underlying the acquisition of predictive properties of cues signaling pain, but conditioned pain-related fear does not result in visceral hyperalgesia or central sensitization.

Brain Areas Involved in Anticipation of Clinically Relevant Pain in Low Back Pain Populations With High Levels of Pain Behavior.

The purpose of this study was to identify neural correlates of pain anticipation in people with nonspecific low back pain (NSLBP) that correlated with pain-related distress and disability, thus providing evidence for mechanisms underlying pain behavior in this population. Thirty NSLBP sufferers, with either high levels of pain behavior or low levels on the basis of Waddell signs, were scanned with functional magnetic resonance imaging while a straight-leg raise (of the side deemed to cause moderate pain in the lower back) was performed. On each trial colored stimuli were presented and used to indicate when the leg definitely would be raised (green; 100% certainty), might be raised (yellow; 50% certainty), or would definitely not be raised (red; 100% certainty). In response to expected versus unexpected pain the group difference in activation between patients with high levels of pain behavior and low levels of pain behavior covaried as a function of anxiety scores in the right insula and pregenual anterior cingulate cortex and as a function of catastrophizing in prefrontal and parietal cortex and hippocampus. The results suggest NSLBP populations with the highest levels of pain-related distress are more likely to attend to and infer threat from innocuous cues, which may contribute to the maintenance of pain behavior associated with some chronic pain states. This article shows a likely neural network for exacerbating pain anticipation in NSLBP contributing to high levels of pain behavior in some people. This information could potentially help clinicians and patients to understand how anticipation of pain may contribute to patient pain and disability.

Early event related fields during visually evoked pain anticipation

ObjectivePain experience is not only a function of somatosensory inputs. Rather, it is strongly influenced by cognitive and affective pathways. Pain anticipatory phenomena, an important limitation to rehabilitative efforts in the chronic state, are processed by associative and limbic networks, along with primary sensory cortices. Characterization of neurophysiological correlates of pain anticipation, particularly during very early stages of neural processing is critical for development of therapeutic interventions. MethodsHere, we utilized magnetoencephalography to study early event-related fields (ERFs) in healthy subjects exposed to a 3s visual countdown task that preceded a painful stimulus, a non-painful stimulus or no stimulus. ResultsWe found that the first countdown cue, but not the last cue, evoked critical ERFs signaling anticipation, attention and alertness to the noxious stimuli. Further, we found that P2 and N2 components were significantly different in response to first-cues that signaled incoming painful stimuli when compared to non-painful or no stimuli. ConclusionsThe findings indicate that early ERFs are relevant neural substrates of pain anticipatory phenomena and could be potentially serve as biomarkers. SignificanceThese measures could assist in the development of neurostimulation approaches aimed at curbing the negative effects of pain anticipation during rehabilitation.

Thermal Pain and Pain Anticipation Induce a Decrease in Microvascular Perfusion in Sickle Cell and Normal Subjects

INTRODUCTION: Sickle cell disease is an inherited blood disorder characterized by vaso-occlusive crises (VOC). HbS in red blood cells (RBC) polymerizes rapidly after it releases oxygen to tissues, causing RBC to become rigid. Anything that decreases flow in the microvasculature increases the chance that this flexible-to-rigid transformation occurs causing the rigid blood cell to lodge in the microvasculature, therefore increasing the chance of vaso-occlusion and the risk of VOC. Although hypoxia and stress are known risk factors for crises, the exact mechanism that initiates VOC events is not well known. We have previously shown that transient hypoxia causes parasympathetic withdrawal and sighs cause vasoconstriction more frequently in SCD subjects than in normal controls. Pain is the hallmark of SCD and is a consequence of VOC but has not been considered as a possible trigger of vasoconstriction that may lead to VOC.OBJECTIVES: To determine if heat induced pain causes decrease in peripheral blood flow (PBF) in SCD.METHODS: 30 SCD and 30 control subjects (healthy and sickle cell traits) were recruited at Children's Hospital Los Angeles (CHLA). Quasi-periodic pulses of pain were induced on the right forearm using TSA-II neuro analyzer heating thermode.We implemented a technique using cross correlation analysis to detect changes in complex microvascular flow signals measured bilaterally on the hands, using laser-Doppler flowmeter (LDF), Peripheral Arterial Tonometer (PAT) and photo-plethysmography (PPG).We also measured the average drop from baseline in the microvascular flow during the heat pain. Data were analyzed using one- and two- sample Student t-test.RESULTS: Data on 53 subjects were analyzed. There was a significant correlation between heat pain pulses and PBF responses, as well as a significant drop in blood flow in all study participants (PPG signal, both p<0.001), indicating that heat pain pulses lead to vasoconstriction.Males had higher correlation (p<0.005) and stronger vasoconstriction (p<0.05) during heat stimuli compared to females. Other Signals (LDF and PAT) had a similar pattern but were less significant.The vasoconstriction response consisted of two components, the first one occurred prior to administration of the painful stimulus indicating that anxiety or anticipation of pain causes significant vasoconstriction. Application of the painful stimulus causes further vasoconstriction.CONCLUSIONS: The findings demonstrate a significant decrease in PBF in both SCD and controls in response to heat pain and possibly to pain anticipation. The decrease in PBF could play a critical role in the genesis of VOC in SCD by markedly prolonging microvascular transit time, increasing the likelihood of red cell entrapment when sickle red cells transform from flexible to rigid. Furthermore, the potent vasoconstriction response to pain in SCD means that pain resulting from VOC could potentially trigger a cascade effect in which vasoconstriction could lead to even more serious VOC. Since regional blood flow is regulated by the autonomic nervous system (ANS), which has been described to be dysfunctional in SCD, our study calls attention to the ANS as a factor in the genesis of crisis in this disorder. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Direct Interactive Public Education by Breast Radiologists About Screening Mammography: Impact on Anxiety and Empowerment

PurposeAnxiety has been called a “harm” of screening mammography. The authors provided direct, interactive education to lay audiences and measured these sessions’ impact on anxiety and any increased understanding of breast cancer screening. MethodsAcademic breast radiologist provided seven 1-hour sessions of structured lectures and question-and-answer periods. Lay language and radiologic images were used to discuss disease background, screening guidelines, and areas of debate. One hundred seventeen participants (mean age, 45 ± 15 years) completed voluntary, anonymous, institutional review board-approved pre and postsession questionnaires relaying their attitudes regarding screening and the impact of the sessions. Results are summarized descriptively. ResultsMean reported anxiety regarding screening (on a scale ranging from 1-5; 1 = no anxiety) was 2.5 ± 1.3. Anxiety was attributed to unknown results (56.4%), anticipation of pain (21.8%), known risk factors (14.5%), general uncertainty (12.7%), waiting for results (9.1%), possibility of more procedures (3.6%), and personal breast cancer history (3.6%). Ninety-seven percent reported that immediate results would lower anxiety (78% of those women indicated a 75%-100% decrease in anxiety); 93% reported that radiologist consultation with images would lower anxiety (75.6% indicated a 75%-100% decrease in anxiety). After the lecture, women reported (on a scale ranging from 1-5) increased understanding of the topic (4.7 ± 0.6), encouragement to screen (4.6 ± 0.7), and reduced anxiety (4.0 ± 1.1). Ninety-seven percent to 100% provided correct responses to these questions: rationale for screening in the absence of family history, recall does not equate to cancer diagnosis, benefit of prior films, and continued importance of physical examination. ConclusionAttendees of radiologist-provided direct public lectures reported decreased anxiety and improved knowledge regarding screening mammography. The resultant reduced anxiety (“harm”) and educational empowerment help enable informed decision making and may promote screening attendance.