Emotional Modulation Of Pain Research Articles

Neural dynamics of pain modulation by emotional valence.

Definitions of human pain acknowledge at least two dimensions of pain, affective and sensory, described as separable and thus potentially differentially modifiable. Using electroencephalography, we investigated perceptual and neural changes of emotional pain modulation in healthy individuals. Painful electrical stimuli were applied after presentation of priming emotional pictures (negative, neutral, positive) and followed by pain intensity and unpleasantness ratings. We found that perceptual and neural event-related potential responses to painful stimulation were significantly modulated by emotional valence. Specifically, pain unpleasantness but not pain intensity ratings were increased when pain was preceded by negative compared to neutral or positive pictures. Amplitudes of N2 were higher when pain was preceded by neutral compared to negative and positive pictures, and P2 amplitudes were higher for negative compared to neutral and positive pictures. In addition, a hierarchical regression analysis revealed that P2 alone and not N2, predicted pain perception. Finally, source analysis showed the anterior cingulate cortex and the thalamus as main spatial clusters accounting for the neural changes in pain processing. These findings provide evidence for a separation of the sensory and affective dimensions of pain and open new perspectives for mechanisms of pain modulation.

Opioid Receptor Mu 1 Gene (OPRM1) A118G Polymorphism and Emotional Modulation of Pain.

The A118G polymorphism in the opioid receptor mu 1 gene (OPRM1) is associated with decreased opioid receptor availability, altered emotion, and increased pain. Given that emotions modulate pain (positive emotions inhibit pain, negative emotions enhance pain), we predicted that G allele carriers would experience impaired emotional modulation of pain compared to non-G allele carriers. Emotional pictures (ie, erotica, neutral, attack) from the International Affective Picture System were used by permission from the authors to experimentally manipulate emotions in 64 adult participants while painful electrocutaneous stimulations were delivered in a cross-sectional study. Ratings of arousal and valence/pleasure were made in response to pictures, and pain ratings and a physiological measure of spinal nociception (ie, nociceptive flexion reflex, NFR) were collected in response to painful stimulations. Secondary analyses were conducted to examine the relationship between the A118G polymorphism and emotional modulation of pain/NFR. Exposure to emotional pictures elicited similar changes in valence, but G-carriers rated erotic pictures as more arousing. In non-carriers, pain was facilitated by attack pictures and pain and NFR were inhibited by erotic pictures relative to neutral pictures. Among G-carriers, pain was facilitated by negative emotional pictures but there was no pain or NFR inhibition by positive emotional pictures. The altered response to pleasant stimuli further supports the role of opioids in appetitive behavior and describes how the A118G polymorphism may prevent carriers from inhibiting pain during pleasure.

The effect of emotion regulation on the emotional modulation of pain and nociceptive flexion reflex.

Positive emotions inhibit pain, whereas negative emotions facilitate pain. Thus, many psychosocial interventions capitalize on this emotion-pain relationship to improve patients' abilities to regulate emotion (ie, reduce negative emotion, increase positive emotion), influence nociception, and manage pain. This study extended the existing literature to examine whether emotion regulation procedures could influence emotional modulation of the nociceptive flexion reflex (NFR), a marker of spinal nociception. To elicit emotion, 2 blocks of pleasant, neutral, and unpleasant pictures were presented. In block 1, participants were asked to passively view pictures during which painful electric stimulations were delivered to evoke pain and the NFR. Valence, arousal, corrugator electromyogram, and skin conductance response were used to measure emotional responses to pictures. To manipulate emotion regulation, participants were randomized to either suppress (downregulate) or enhance (upregulate) their emotion during block 2 (other procedures same as block 1). Instructions to suppress decreased subjective and physiological responding to emotional pictures, reduced emotional modulation of pain, and generally decreased NFR magnitude (regardless of picture content). Instructions to enhance emotion increased subjective responding to emotional pictures but did not alter physiological responding to pictures or emotional modulation of pain/NFR in predictable ways. Results imply that downregulation/suppression of negative emotions may work best to reduce pain facilitation. Furthermore, this study contributes to the existing literature that shows that pain and pain signaling is tightly coupled with emotional states and that emotion regulation can impact pain perception.

Pain and masochistic behaviour: The role of descending modulation.

The mechanisms of pain perception in individuals with masochistic behaviour (MB) remain poorly documented. We hypothesized that MB is associated with context-specific changes in descending pain modulation. We compared the effects of four standardized sets of images with positive (erotic), negative (mutilations), masochistic or neutral emotional valences on the RIII nociceptive reflex evoked by electrical stimulation of the sural nerve and recorded on the ipsilateral biceps femoris in 15 controls and 15 men routinely engaging in MB. We systematically assessed the RIII reflex threshold and recruitment curves (up to the tolerance threshold), thermal (heat and cold) pain thresholds measured on the upper and lower limbs and responses to the pain sensitivity questionnaire, to compare basal pain perception between our two groups of participants. We also assessed anxiety, depression, empathy, alexithymia, high sensation seeking and catastrophizing, to investigate their potential influence on the emotional modulation of pain. Thermal pain thresholds, RIII reflex recruitment curves, and responses to the psychological and pain sensitivity questionnaires were similar in the two groups. Neutral, positive and negative images modulated the RIII reflex similarly in the two groups. By contrast, masochistic images induced a significant (p< 0.01) decrease in RIII reflex responses in subjects with MB, whereas it tended to increase these responses in control subjects. Our data suggest that psychological profile, basal pain sensitivity and the emotional modulation of pain are normal in individuals with MB but that these subjects selectively engage descending pain inhibition in the masochistic context. Decrease pain perception related to masochistic behaviours is associated with specific activation of descending pain inhibition.

Carpal tunnel surgery dampens thalamocortical and normalizes corticocortical functional connectivity.

Carpal tunnel syndrome is the most common entrapment neuropathy and is associated with altered brain function and structure. However, little is understood of the central mechanisms associated with its pain, symptom presentation, and treatment-related resolution. This longitudinal study evaluated carpal tunnel syndrome-related alterations in brain network communication and relationships to behavioural signs of central sensitization before and after carpal tunnel release surgery. We tested the hypothesis that carpal tunnel syndrome is associated with condition- and treatment-related plasticity in brain regions involved in somatosensation. We used quantitative sensory testing and clinical and pain questionnaires to assess sensory and pain function in 25 patients with carpal tunnel syndrome before (18 women, 7 men) and after (n = 16) surgery, and 25 sex- and age-matched healthy controls. We also acquired resting-state functional MRI to determine functional connectivity of two key nodes in the somatosensory system, the thalamus and primary somatosensory cortex. Seed-to-whole brain resting-state static functional connectivity analyses revealed abnormally low functional connectivity for the hand area of the primary somatosensory cortex with the contralateral somatosensory association cortex (supramarginal gyrus) before surgery (P < 0.01). After clinically effective surgery: (i) Primary somatosensory functional connectivity was normalized with the contralateral somatosensory association cortex and reduced with the dorsolateral prefrontal cortex (a region associated with cognitive and emotional modulation of pain) and primary visual areas (P < 0.001) from pre-op levels; and (ii) Functional connectivity of the thalamus with the primary somatosensory and motor cortices was attenuated from pre-op levels (P < 0.001) but did not correlate with temporal summation of pain (a behavioural measure of central sensitization) or clinical measures. This study is the first to reveal treatment-related neuroplasticity in resting-state functional connectivity of the somatosensory system in carpal tunnel syndrome. The findings of dysfunctional resting-state functional connectivity point to aberrant neural synchrony between the brain’s representation of the hand with regions involved in processing and integrating tactile and nociceptive stimuli and proprioception in carpal tunnel syndrome. Aberrant neural communication between the primary somatosensory hand area and the dorsolateral prefrontal cortex could reflect increased attention to pain, paraesthesia, and altered sensation in the hand. Finally, reduced thalamocortical functional connectivity after surgery may reflect central plasticity in response to the resolution of abnormal sensory signals from the periphery. Our findings support the concept of underlying brain contributions to this peripheral neuropathy, specifically aberrant thalamocortical and corticocortical communication, and point to potential central therapeutic targets to complement peripheral treatments.

Cerebral Peak Alpha Frequency Is Not Associated with Emotional Modulation of Pain

Chronic pain is a tremendous burden, resulting in increased psychological distress and disability. To prevent and address chronic pain before it develops, more research into chronic pain risk markers is needed. Cerebral peak alpha frequency (PAF) is a promising risk marker as it is associated with pain sensitivity, postsurgical pain outcomes, and several chronic pain conditions. However, it is still unclear how cerebral PAF is related to nociceptive processing and pain modulation. The purpose of this study was to examine the relationship between PAF and one type of pain modulation, emotional modulation of pain. To this end, a well validated affective picture viewing paradigm was used during which 24 IAPS pictures (8 mutilation, 8 neutral, 8 erotica pictures) were presented and painful electric stimulations were delivered. In addition to subjective pain ratings, physiological responses to electric stimulations were recorded at the spinal level (assessed by the nociceptive flexion reflex [NFR]) and the supraspinal level (assessed by the pain-evoked potentials [N2 & P2]). EEG was recorded during a 3-minute period of rest and PAF was extracted using the center of gravity method. The sample consisted of 37 (23 women) healthy, right-handed, pain-free participants. The degree of pain inhibition during erotica was assessed using a change score calculating the difference in pain, NFR, and N2/P2 during erotica relative to neutral pictures. Conversely, the degree of pain facilitation during mutilation was assessed using a change score calculating the difference in pain, NFR, and N2/P2 during mutilation relative to neutral pictures. PAF was entered as predictor in multiple regression analyses that controlled for age and sex, with change scores (erotica-neutral; mutilation-neutral) as outcome variables. Results found no significant association between PAF and emotional modulation. This suggests that any relationship between PAF and chronic pain risk is not due to emotional modulation of pain.

Heart Rate Variability Is Not Associated with Altered Emotional Modulation of Pain or Spinal Nociception.

Heart rate variability (HRV) is a physiological measure of beat-to-beat variation in time between heartbeats that reflects competing influences of the sympathetic and parasympathetic branches of the autonomic nervous system (ANS). Research suggests that both ANS branches, and consequently, HRV, are regulated by the central autonomic network (CAN), a widely distributed and interconnected circuit of cortical, limbic, and brainstem areas that modulate ANS activity to meet environmental demands based on current internal physiological conditions. Given its role in modifying internal states, the CAN has been implicated as an important circuit in emotion regulation, and previous researchers have hypothesized that HRV may be a physiological marker related to emotion regulation ability. Indeed, low HRV has been associated with disorders characterized by emotion dysregulation (i.e., depressive and anxiety disorders.) Thus, the current study was conducted to determine whether HRV (calculated using the root mean square of successive differences [RMSSD] and autoregressive high frequency spectral power), divided into tertiles reflecting low, medium, and high levels of HRV, was associated with altered emotional modulation of pain or spinal nociception (assessed from the nociceptive flexion reflex, NFR) during and emotional picture-viewing paradigm known as emotional controls of nociception (ECON). The sample was comprised of 261 healthy, pain-free men and women. It was hypothesized that low HRV would be associated with altered emotional modulation of pain/NFR relative to the other tertile groups for both measures of HRV, with greater facilitation of pain/NFR during negatively valenced pictures and impaired inhibition of pain/NFR during positively valenced pictures. Multilevel modeling analyses revealed that emotional modulation of pain and spinal nociception were not moderated by HRV. Thus, HRV does not appear to promote amplification of pain and nociception via emotional processes, at least not in healthy individuals. These research results were supported by a grant titled, "Native American Pain Disparities: Exploring Nociceptive Processing Differences" (Project Number: 1R01MD007807-01).

The relationship between sleep quality and emotional modulation of spinal, supraspinal, and perceptual measures of pain

Poor sleep quality is often comorbid with chronic pain. Research has also shown that poor and disrupted sleep may increase risk for chronic pain by promoting pronociceptive processes. This could occur through disrupted emotional modulation of pain since poor sleep can impact emotional experience and emotional experience modulates pain and nociception. To assess the pain system, nociceptive flexion reflexes (spinal level), pain-evoked potentials (supraspinal level), and perceived pain were recorded during an emotional picture-viewing task in which 37 healthy individuals received painful electric stimulations. The Pittsburgh Sleep Quality Index assessed sleep quality. Individuals with poor sleep quality were unable to inhibit signals at the spinal level in response to positive pictures, whereas emotional modulation of supraspinal nociception and pain perception remained unaffected by sleep quality. This suggests poor sleep quality may promote pronociception by impairing descending, emotional modulation of spinal nociception.

Transcranial Direct Current Stimulation of the Dorsolateral Prefrontal Cortex Alters Emotional Modulation of Spinal Nociception

Emotion has a strong modulatory effect on pain perception and spinal nociception. Pleasure inhibits pain and nociception, whereas displeasure facilitates pain and nociception. Dysregulation of this system has been implicated in development and maintenance of chronic pain. The current study sought to examine whether emotional modulation of pain could be altered through the use of transcranial direct current stimulation (tDCS) to enhance (via anodal stimulation) or depress (via cathodal stimulation) cortical excitability in the dorsolateral prefrontal cortex. Thirty-two participants (15 female, 17 male) received anodal, cathodal, and sham tDCS on three separate occasions, followed immediately by testing to examine the impact of pleasant and unpleasant images on pain and nociceptive flexion reflex (NFR) responses to electrocutaneous stimulation. Results indicated that tDCS modulated the effect of image content on NFR, F(2, 2175.06) = 3.20, P= .04, with the expected linear slope following anodal stimulation (ie, pleasant < neutral < unpleasant) but not cathodal stimulation. These findings provide novel evidence that the dorsolateral prefrontal cortex is critical to emotional modulation of spinal nociception. Moreover, the results suggest a physiological basis for a previously identified phenotype associated with risk for chronic pain and thus a potentially new target for chronic pain prevention efforts. PerspectiveThis study demonstrated that reduction of dorsolateral prefrontal cortical excitability by transcranial direct current stimulation attenuates the impact of emotional image viewing on nociceptive reflex activity during painful electrocutaneous stimulation. This result confirms there is cortical involvement in emotional modulation of spinal nociception and opens avenues for future clinical research.

Functional connectivity of the amygdala is linked to individual differences in emotional pain facilitation.

The amygdala is central to emotional processing of sensory stimuli, including pain. Because recent findings suggest that individual differences in emotional processes play a part in the development of chronic pain, a better understanding of the individual patterns of functional connectivity that makes individuals susceptible to emotionally modulated facilitation of pain is needed. We therefore investigated the neural correlates of individual differences in emotional pain facilitation using resting-state functional magnetic resonance imaging (rs-fMRI) with an amygdala seed. Thirty-seven participants took part in 3 separate sessions, during which pain sensitivity was tested (session 1), participants underwent rs-fMRI (session 2), and emotional pain modulation was assessed (session 3). The amygdala served as seed for the rs-fMRI analysis, and whole-brain voxel-wise connectivity was tested. Pain modulatory scores were entered as regressor for the group analysis. Stronger connectivity of the amygdala to S1/M1, S2/operculum, and posterior parietal cortex at rest characterized individuals who showed greater pain facilitation by negative emotions. When comparing the amygdala networks associated with pain unpleasantness and with pain-intensity modulation, most of the identified areas were equally related to either pain rating type; only amygdala connectivity to S1/M1 was found to predict pain-intensity modulation specifically. We demonstrate that trait-like patterns of functional connectivity between amygdala and cortical regions involved in sensory and motor responses are associated with the individual amplitude of pain facilitation by negative emotional states. Our results are an early step toward improved understanding of the mechanisms that give rise to individual differences in emotional pain modulation.

Unique brain regions involved in positive versus negative emotional modulation of pain.

Background and aims Research has shown that negative emotions increase perceived pain whereas positive emotions reduce pain. Here we aim to investigate the neural mechanisms underlying this phenomenon. Methods While undergoing functional magnetic resonance imaging of the brain, 20 healthy adult females were presented with negative, neutral, and positive emotion-evoking visual stimuli in combination with the presentation of a noxious thermal stimulus to the hand. Participants rated the intensity and unpleasantness of the noxious thermal stimulus during each of the valence conditions. General linear model analyses were performed on the imaging data for each valence condition and specific contrasts were run. Results Significant differences were detected for the emotional modulation of pain (EMP) between the positive and negative conditions. Unique to the positive condition, there was increased activity in the inferior parietal, parahippocampal/perirhinal, precuneus/superior parietal, and the prefrontal cortices. Unique to the negative condition, there was increased activity in anterior and posterior cingulate and angular gyrus. Conclusions Positive and negative EMP appear to involve different brain regions. Implications Although there is some overlap in the brain regions involved in the positive and negative EMP, brain regions unique to each condition are identified and, moreover, the regions identified are involved in internal and external focus, respectively, pointing to a potential mechanism underlying this phenomenon.

Anger Inhibition and Pain Modulation.

The tendency to inhibit anger (anger-in) is associated with increased pain. This relationship may be explained by the negative affectivity hypothesis (anger-in increases negative affect that increases pain). Alternatively, it may be explained by the cognitive resource hypothesis (inhibiting anger limits attentional resources for pain modulation). A well-validated picture-viewing paradigm was used in 98 healthy, pain-free individuals who were low or high on anger-in to study the effects of anger-in on emotional modulation of pain and attentional modulation of pain. Painful electrocutaneous stimulations were delivered during and in between pictures to evoke pain and the nociceptive flexion reflex (NFR; a physiological correlate of spinal nociception). Subjective and physiological measures of valence (ratings, facial/corrugator electromyogram) and arousal (ratings, skin conductance) were used to assess reactivity to pictures and emotional inhibition in the high anger-in group. The high anger-in group reported less unpleasantness, showed less facial displays of negative affect in response to unpleasant pictures, and reported greater arousal to the pleasant pictures. Despite this, both groups experienced similar emotional modulation of pain/NFR. By contrast, the high anger-in group did not show attentional modulation of pain. These findings support the cognitive resource hypothesis and suggest that overuse of emotional inhibition in high anger-in individuals could contribute to cognitive resource deficits that in turn contribute to pain risk. Moreover, anger-in likely influenced pain processing predominantly via supraspinal (e.g., cortico-cortical) mechanisms because only pain, but not NFR, was associated with anger-in.

(261) Does Anger Inhibition Alter Pain Modulation?

The tendency to inhibit anger (anger-in) is associated with increased pain. This relationship may be explained by the negative affectivity hypothesis such that those with high anger-in experience increased negative affectivity and thus increased pain (because negative affect enhances pain). Alternatively, this relationship may be explained by the cognitive resource hypothesis such that anger-in limits attentional resources normally available for pain modulation. The present study examined these competing hypotheses in healthy, pain-free participants using a well-validated picture viewing paradigm (ie, Emotional Controls of Nociception, ECON). ECON is a paradigm in which painful, electrocutaneous stimulations are delivered during and in between pictures of emotional content (mutilation, neutral, and erotica). Pain ratings were assessed in response to electric stimuli. This allows for the assessment of emotional modulation of pain by comparing pain evoked during mutilation and erotic pictures to pain evoked during neutral pictures. Additionally, ECON allows for the assessment of attentional modulation of pain by comparing pain evoked during neutral pictures (distraction) to pain evoked in the absence of pictures (control). Prior to ECON, participants filled out the Anger Expression Inventory to assess their tendency to inhibit anger and 2 groups were formed (high anger-in, N = 71 and low anger-in, N = 27) from their responses (ie, +/- 1SD from the normative mean of anger-in). Results found that both groups demonstrated similar emotional modulation of pain. By contrast, persons in the low anger-in group displayed attentional modulation of pain, whereas persons in the high anger-in group failed to attentionally modulate pain. These findings suggest that cognitive resource deficits in high anger-in individuals may contribute to increased pain risk.

Emotional Modulation of Pain and Spinal Nociception in Sexual Assault Survivors.

Sexual assault (SA) is associated with an increased risk for chronic pain and affective distress. Given that emotional processes modulate pain (e.g., negative emotions enhance pain, positive emotions inhibit pain), increased pain risk in SA survivors could stem from a disruption of emotional modulation processes. A well-validated affective picture-viewing paradigm was used to study emotional modulation of pain in 33 healthy, pain-free SA survivors and a control group of 33 healthy, pain-free individuals with no reported history of SA (matched on age, sex, race, and number of non-SA traumas). Unpleasant (mutilation), neutral, and pleasant (erotic) pictures were presented, while painful electrocutaneous stimulations were delivered at the ankle. Pain intensity ratings and nociceptive flexion reflex (NFR) magnitudes (a physiologic measure of spinal nociception) were recorded in response to electric stimuli. Multilevel models were used to analyze the data with group (SA versus non-SA) and content (mutilation, neutral, erotic) as independent variables. Both groups demonstrated similar emotional modulation of pain (FGroupbyContent(2,646.52) = 0.44, p = .65), but a main effect of group (FGroup(1,65.42) = 4.24, p = .043) indicated the SA group experienced more overall pain from electric stimuli (hyperalgesia). A significant group by content interaction for NFR (p = .035) indicated that emotional modulation of NFR was present for the non-SA group (FContentSimpleEffect(2,684.55) = 12.43, p < .001), but not the SA group (FContentSimpleEffect(2,683.38) = 1.71, p = .18). These findings suggest that SA survivors have difficulty emotionally engaging brain-to-spinal cord mechanisms to modulate spinal nociception. A disruption of descending inhibition plus hyperalgesia could contribute to comorbidity between sexual trauma and chronic pain.

Diversity in the emotional modulation of pain perception: An account of individual variability.

While emotional state has been shown to modulate pain perception, there has been little consideration for the individual variability in this effect, or what factors may contribute to individual-level differences. The objective of this study was to characterize the variability in emotional modulation of pain in a healthy sample. Twenty-five healthy, adult females participated in a heat pain-rating task. After calibration of the appropriate temperature for each participant, the pain-rating task was combined with viewing of positive, neutral, or negative valence images. Participants rated pain intensity and unpleasantness of the painful stimulus. The magnitude of the effect for emotional modulation of pain was markedly variable across individuals. Some participants exhibited greater pain relief from the positive emotional stimuli while others were more susceptible to pain amplification from the negative emotional stimuli. There were also significant correlations between emotional modulation of pain and specific psychological measures (depression and anxiety). Overall, inducing a positive emotional state mitigates pain perception, while negative emotional state amplifies it. The magnitudes of these separate pain-modulating effects, however, vary across individuals, and are associated with individual levels of depressive and anxious feelings, even within a non-clinical population. The opposite effects of valence on pain amplification and modulation revealed in this study are novel. This study shows that emotional modulation of pain varies markedly across individuals and is related to psychological factors including depression and anxiety. Examining this link in healthy individuals may inform our understanding of the comorbidity between pain and depression/anxiety.

(346) Is resting blood pressure associated with emotional modulation of pain?

(346) Is resting blood pressure associated with emotional modulation of pain?

Increased Low- and High-Frequency Oscillatory Activity in the Prefrontal Cortex of Fibromyalgia Patients.

Recent human neuroimaging studies have suggested that fibromyalgia (FM), a chronic widespread pain disorder, exhibits altered thalamic structure and function. Since the thalamus has extensive reciprocal connection with the cortex, structural and functional thalamic alterations in FM might be linked to aberrant thalamocortical oscillation. This study investigated the presence of abnormal brain rhythmicity in low- and high-frequency bands during resting state in patients with FM and their relationship to clinical pain symptom. Spontaneous magnetoencephalography (MEG) activity was recorded in 18 females with FM and 18 age- and sex-matched healthy control (HC) subjects. The most remarkable finding was that FM patients had general increases in theta, beta and gamma power along with a slowing of the dominant alpha peak. Increased spectral powers in the theta-band were primarily localized to the left dorsolateral prefrontal (DLPFC) and orbitofrontal cortex (OFC). Beta and gamma over-activation were localized to insular, primary motor and primary and secondary somatosensory (S2) cortices, as well as the DLPFC and OFC. Furthermore, enhanced high-frequency oscillatory activities in the DLPFC and OFC were associated with higher affective pain scores in patients with FM. Our results demonstrate that FM patients feature enhanced low- and high-frequency oscillatory activity in the brain areas related to cognitive and emotional modulation of pain. Increased low- and high-frequency activity of the prefrontal cortex may contribute to persistent perception of pain in FM. Therapeutic intervention based on manipulating neural oscillation to restore normal thalamocortical rhythmicity may be beneficial to pain relief in FM.

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.

Cognitive and Emotional Modulation of Pain

Introduction Pain is a personal experience that widely varies between people and even within an individual. It dependson numerous factors which can change over the time. The psychological state of the person, such as cognitive and emotional factors, has an important influence on pain perception. In chronic pain it can occur anatomical and functional alterations in regions involved both in pain control and cognitive or emotional functioning. Aims The authors aim to clarify the role of cognition and emotion in pain modulation and its disruption in chronic pain. Methods Literature review in PubMed database using the following key words: 'pain”, 'chronic pain”, 'pain modulation”,'emotion” and 'cognition”. Discussion Recent studies demonstrate that cognitive – attentional variations – and emotional factors can modulate pain perception. The attentional state changes the perceived intensity of pain, while emotional state changes the perceived unpleasantness of the pain without changing its intensity. Such evidence takes usback to that cognition and emotion modulates pain by different mechanisms. Emotional state activates anterior cingulatecortex, prefrontal cortex and periaqueductal gray. On the other hand, attention activates projections from the superiorparietal lobe to the primary somatosensory cortex and insula. Cross-sectional studies have demonstrated that chronicpain can change these modulatory pathways. Conclusions Despite the personal and interpersonal differences in pain perception, it is established that cognitive and emotional factors are important in pain modulation and perception. However, in chronic pain there are changes in these mechanisms which need to be clarified.

Affective disturbance associated with premenstrual dysphoric disorder does not disrupt emotional modulation of pain and spinal nociception

In healthy individuals, emotions modulate pain and spinal nociception according to a valence linear trend (ie, pain/nociception is highest during negative emotions and lowest during positive emotions). However, emerging evidence suggests that emotional modulation of pain (but not spinal nociception) is disrupted in fibromyalgia and disorders associated with chronic pain risk (eg, major depression, insomnia). The present study attempted to extend this work and to examine whether women with premenstrual dysphoric disorder (PMDD), a cyclical syndrome associated with debilitating affective symptoms during the late-luteal (premenstrual) phase of the menstrual cycle, is also associated with disrupted emotional modulation of pain. To do so, an affective picture-viewing procedure was used to study emotional modulation of pain and spinal nociception in 14 women with PMDD and 14 control women during mid-follicular, ovulatory, and late-luteal phases of the menstrual cycle (verified by salivary hormone levels and luteinizing hormone tests). At each phase, mutilation, neutral, and erotic pictures were presented to manipulate emotion. During picture viewing, suprathreshold electrocutaneous stimuli were presented to evoke pain and the nociceptive flexion reflex (NFR; a physiological measure of spinal nociception). Statistically powerful linear mixed model analyses confirmed that pictures evoked the intended emotional states in both groups across all menstrual phases. Furthermore, emotion modulated pain and NFR according to a valence linear trend in both groups and across all menstrual phases. Thus, PMDD-related affective disturbance is not associated with a failure to emotionally modulate pain, suggesting that PMDD does not share this pain phenotype with major depression, insomnia, and fibromyalgia.