The effect of the menstrual cycle on affective modulation of pain and nociception in healthy women

Research indicates pain may be influenced by the menstrual cycle. While the mechanisms underlying these effects are unclear, it is possible that menstrual phase-related changes in endogenous pain modulation contribute. The present study used well-validated methods to study affective modulation of pain and the nociceptive flexion reflex (NFR) in healthy women during two menstrual phases (mid-follicular vs. late-luteal). Women (N = 41) tracked their menstrual phases for three complete cycles and were asked to attend two laboratory testing sessions in the second and third cycles to assess affective modulation of pain and nociception (testing order counterbalanced). Menstrual phase was assessed from daily diaries, luteinizing hormone tests, and basal body temperature. At each session, emotionally charged pictures were presented and suprathreshold electrocutaneous stimulations were delivered during and in between pictures. Subjective and physiological emotional reactions were recorded in response to each picture and pain ratings and NFRs were recorded in response to each suprathreshold stimulus. Results suggested pictures effectively manipulated emotion in both menstrual phases. Moreover, arousing unpleasant pictures enhanced pain and NFR, whereas arousing pleasant pictures inhibited pain and NFR. These modulatory effects were similar in both menstrual phases. Together, these findings suggest that affective engagement of corticospinal mechanisms does not differ across these phases of the menstrual cycle. However, future research is needed to directly assess the relationship between affective modulation of pain/nociception and inter- and intra-individual differences in ovarian hormones and to extend these findings to women who suffer from menstrual cycle-related pain (e.g., premenstrual dysphoric disorder, fibromyalgia).     

Emotional control of nociceptive reactions (ECON): Do affective valence and arousal play a role?

Prior research suggests emotional picture-viewing modulates motoric (nociceptive flexion reflex), autonomic (skin conductance response, heart rate acceleration), and subjective (pain rating) reactions to noxious electrodermal stimulation. The present study sought to determine whether emotional valence and arousal contribute to nociception modulation. To do so, pictures varying in emotional content (erotica, food, neutral, loss, attack) were chosen to manipulate emotional valence (pleasant=erotic and food; unpleasant=loss and attack) and arousal (low=food and loss; moderate=erotica and attack). Pictures were presented in pseudorandom order to elicit emotional processing while noxious electric stimulations were delivered to the sural nerve. Nociceptive flexion reflex (NFR) magnitude, skin conductance response (SCR), heart rate (HR) acceleration, and subjective pain ratings to each stimulation were measured, standardized, averaged by picture content, and analyzed. Results suggested that picture-viewing explained 52% of the variance in the multivariate combination of the nociceptive reactions and modulated them in parallel. Pleasant pictures inhibited reactions, whereas unpleasant pictures enhanced them. However, only erotica and attack pictures elicited significant modulation relative to neutral pictures, suggesting arousal also contributed. An exploratory multilevel analysis also supported this conclusion. Together, these data suggest emotional control of nociceptive reactions (ECON) is associated with a valence-by-arousal interaction. Implications of these findings for how emotional picture-viewing can be used to study supraspinal modulation are discussed.     

Are There Sex Differences in Affective Modulation of Spinal Nociception and Pain?

Sex differences in the processing and experience of emotion exist. The present study examined whether sex differences in emotion lead to sex differences in affective modulation of pain and spinal nociception (assessed by nociceptive flexion reflex, NFR). Participants were healthy men (n = 47) and women (n = 73). Prior to affective modulation testing, electrocutaneous pain sensitivity was assessed (NFR threshold, pain threshold, pain tolerance). Affective modulation of pain and NFR was then assessed by presenting pictures that vary in emotional valence and arousal (mutilation, attack, death, neutral, families, adventure, erotica) during which suprathreshold electrocutaneous stimulations were delivered. Subjective emotional reactions were assessed after every picture, and nociceptive reactions were assessed after every suprathreshold stimulus. Results indicated women had greater pain sensitivity and also responded more negatively to attack pictures and less positively to erotic pictures. But despite these differences, affective modulation of pain/NFR was not moderated by sex: erotic pictures inhibited pain/NFR and mutilation pictures enhanced pain/NFR. Together, this implies subjective emotional experience does not completely mediate picture-evoked modulation of pain/NFR, a supposition that was further supported by exploratory analyses that demonstrated picture-evoked modulation of pain/NFR was present even after controlling for intra- and inter-individual differences in emotional reactions to pictures. Implications and limitations of these findings are discussed.     

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.     

Emotional modulation of pain and spinal nociception in persons with major depressive disorder (MDD)

Major depressive disorder (MDD) is associated with risk for chronic pain, but the mechanisms contributing to the MDD and pain relationship are unclear. To examine whether disrupted emotional modulation of pain might contribute, this study assessed emotional processing and emotional modulation of pain in healthy controls and unmedicated persons with MDD (14 MDD, 14 controls). Emotionally charged pictures (erotica, neutral, mutilation) were presented in 4 blocks. Two blocks assessed physiological-emotional reactions (pleasure/arousal ratings, corrugator electromyography (EMG), startle modulation, skin conductance) in the absence of pain and 2 blocks assessed emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations. Results indicated pictures generally evoked the intended emotional responses; erotic pictures elicited pleasure, subjective arousal, and smaller startle magnitudes, whereas mutilation pictures elicited displeasure, corrugator EMG activation, and subjective/physiological arousal. However, emotional processing was partially disrupted in MDD, as evidenced by a blunted pleasure response to erotica and a failure to modulate startle according to a valence linear trend. Furthermore, emotional modulation of pain was observed in controls but not MDD, even though there were no group differences in NFR threshold or emotional modulation of NFR. Together, these results suggest supraspinal processes associated with emotion processing and emotional modulation of pain may be disrupted in MDD, but brain to spinal cord processes that modulate spinal nociception are intact. Thus, emotional modulation of pain deficits may be a phenotypic marker for future pain risk in MDD.     

Modulation of the human nociceptive flexion reflex by pleasant and unpleasant odors

The nociceptive withdrawal reflex (NWR), a defensive response that allows withdrawal from a noxious stimulus, is a reliable index of spinal nociception in humans. It has been shown that various kinds of stimuli (emotional, visual, auditory) can modulate the transmission and perception of pain. The aim of the present study was to evaluate, by means of the NWR, the modulatory effect on the spinal circuitry of olfactory stimuli with different emotional valence. The magnitude of the NWR elicited by electrical stimulation of the sural nerve was measured while 18 subjects (9 women, 9 men) smelled pleasant, unpleasant, or neutral odors. The NWR was conditioned by odor probe with interstimulus intervals (ISIs) of 500 ms and 1,500 ms. The magnitude of NWR was significantly greater after the unpleasant odor probe (P <.001) and reduced following the pleasant odor probe (P < .001) at both ISIs. A significant effect of olfactory stimuli on subjective pain ratings were found at both ISIs for pleasant vs unpleasant odors (P < .000), and for both pleasant and unpleasant odors vs neutral and basal conditions (P < .000). No statistical differences in subjective pain ratings at different ISIs were found. Consistent with the notion that NWR magnitude and pain perception can be modulated by stimuli with different emotional valence, these results show that olfactory stimuli, too, can modulate spinal nociception in humans.     

Emotional modulation of spinal nociception and pain: the impact of predictable noxious stimulation

Recent evidence suggests that emotional picture-viewing is a reliable method of engaging descending modulation of spinal nociception. The present study attempted to replicate these findings and determine the effect of noxious stimulus predictability. Participants viewed pictures from the International Affective Picture System (IAPS), during which pain and nociceptive flexion reflexes (NFR) were elicited by electric shocks delivered to the sural nerve. For half of the participants (n=25) shocks were preceded by a cue (predictable), whereas the other half received no cue (unpredictable). Results suggested emotion was successfully induced by pictures, but the effect of picture-viewing on the NFR was moderated by the predictability of the shocks. When shock was unpredictable, spinal nociception (NFR) and pain ratings were modulated in parallel. Specifically, pain and NFR magnitudes were lower during pleasant emotions and higher during unpleasant emotions. However, when shocks were predictable, only pain was modulated in this way. NFRs from predictable shocks were not altered by pictures. Further, exploratory analyses found that pain ratings, but not NFRs, were lower during predictable shocks. These data suggest emotional picture-viewing is a reliable method of engaging descending modulation of spinal nociception. However, descending modulation could not be detected in NFRs resulting from predictable noxious stimuli. Although preliminary, this study implies that separate mechanisms are responsible for emotional modulation of nociception at spinal vs. supraspinal levels, and that predictable noxious events may disengage modulation at the spinal level. The current paradigm could serve as a useful tool for studying descending modulation.     

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.     

Emotional modulation of pain and spinal nociception in fibromyalgia

Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (eg, depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain-free controls (HC). Mutilation, neutral, and erotic pictures were presented in 4 blocks; 2 blocks assessed only physiological-emotional reactions (ie, pleasure/arousal ratings, corrugator electromyography, startle modulation, skin conductance) in the absence of pain, and 2 blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (eg, reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all 3 groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes.     

Using multilevel growth curve modeling to examine emotional modulation of temporal summation of pain (TS-pain) and the nociceptive flexion reflex (TS-NFR)

Emotion can modulate pain and spinal nociception, and correlational data suggest that cognitive-emotional processes can facilitate wind-up-like phenomena (ie, temporal summation of pain). However, there have been no experimental studies that manipulated emotion to determine whether within-subject changes in emotion influence temporal summation of pain (TS-pain) and the nociceptive flexion reflex (TS-NFR, a physiological measure of spinal nociception). The present study presented a series of emotionally charged pictures (mutilation, neutral, erotic) during which electric stimuli at 2 Hz were delivered to the sural nerve to evoke TS-pain and TS-NFR. Participants (n = 46 healthy; 32 female) were asked to rate their emotional reactions to pictures as a manipulation check. Pain outcomes were analyzed using statistically powerful multilevel growth curve models. Results indicated that emotional state was effectively manipulated. Further, emotion modulated the overall level of pain and NFR; pain and NFR were highest during mutilation and lowest during erotic pictures. Although pain and NFR both summated in response to the 2-Hz stimulation series, the magnitude of pain summation (TS-pain) and NFR summation (TS-NFR) was not modulated by picture-viewing. These results imply that, at least in healthy humans, within-subject changes in emotions do not promote central sensitization via amplification of temporal summation. However, future studies are needed to determine whether these findings generalize to clinical populations (eg, chronic pain).     

Supraspinal modulation of trigeminal nociception and pain

Objective.— This study examined modulation of trigeminal pain/nociception by 2 supraspinal mechanisms: emotional controls of nociception and diffuse noxious inhibitory controls. Background.— Prior research suggests emotional picture viewing (emotional controls) and tonic noxious stimuli (diffuse noxious inhibitory controls) engage supraspinal mechanisms to modulate pain and nociceptive processes. It is currently unknown, however, whether emotional controls modulate trigeminal pain and nociception. Additionally, the influences of emotional controls and diffuse noxious inhibitory controls have not been compared in the same group of participants. Methods.— Noxious electrodermal stimuli were delivered to the trigeminal nerve using a concentric electrode designed to selectively activate nociceptive fibers. Trigeminal nociception and pain were assessed (34 participants) from the nociceptive blink reflex and pain ratings, respectively. Emotional controls were engaged by presentation of standardized picture stimuli (pleasant, neutral, and unpleasant) shown to reliably evoke pleasure-induced inhibition and displeasure-induced facilitation of pain and nociception. Diffuse noxious inhibitory controls were engaged with a forearm ischemia task. Results.— Trigeminal pain (self-report ratings) and nociception (blinks) were facilitated by unpleasant pictures and inhibited by pleasant pictures. Emotion induction (as assessed from trend analysis) explained 51% of the variance in trigeminal pain and 25% of the variance in trigeminal nociception. Additionally, forearm ischemia inhibited trigeminal pain but not nociception. The baseline vs ischemia comparison explained 17% of the variance in pain report and 0.1% of the variance in blinks. Supraspinal modulation by emotional controls and diffuse noxious inhibitory controls were uncorrelated. Conclusions.— Emotional controls and diffuse noxious inhibitory controls modulated trigeminal pain and emotional controls modulated trigeminal nociception. These procedures can be used to study supraspinal modulation of nociceptive processing in disorders of the trigeminal pain system, including headache.     

The modulation of pain by attention and emotion: A dissociation of perceptual and spinal nociceptive processes

Emotions and attention have been shown to influence the perception of pain and several psychophysiological studies have suggested an implication of descending modulatory mechanisms to explain these effects. However, the specificity of the neurophysiological mechanisms underlying the emotional and attentional modulation of pain still remains unclear. In order to differentiate the supra‐spinal and spinal mechanisms involved in emotional and attentional modulation of pain, we measured pain perception (self‐ratings) and the RIII reflex in healthy volunteers during the presentation of pleasant, unpleasant and neutral pictures, as well as during a baseline condition with no visual distractor (Experiment 1). In a second experiment, we manipulated the emotional arousal induced by pleasant and unpleasant pictures in order to compare more directly the effects of distraction and arousal. Whereas emotional valence influenced pain and the amplitude of the RIII reflex in the same direction (negative>positive), distraction by neutral pictures reduced pain but increased the RIII reflex relative to baseline. Increased arousal further potentiated the effects of negative valence on both pain and the RIII reflex and the effects of positive emotions on pain, as previously reported. However, arousal did not potentiate the inhibitory effect of positive pictures on the RIII and seems insufficient to account for the effect of distraction on the RIII. Overall, these data provide further evidence that attention and emotion modulate pain through partially dissociable neurophysiological mechanisms.     

Behavioral Inhibition and Behavioral Activation are Related to Habituation of Nociceptive Flexion Reflex,but Not Pain Ratings

Habituation (ie, decreases in responding) and sensitization (ie, increases in responding) after prolonged or repeated exposures to a fixed stimulus have been identified as important in adaptation to repeated or prolonged noxious stimulation. Determinants of habituation or sensitization are poorly understood, and experimental investigation of habituation of pain ratings have generally relied on pain reports and statistical techniques that average responses across a group of participants. Using a cross-sectional design, the current study used multilevel growth curve analyses to examine changes in the nociceptive flexion reflex (NFR), a spinal nociceptive withdrawal reflex, and pain ratings in response to 12 repeated, constant intensity, noxious electrocutaneous stimuli. Unconditional growth curve models indicated that, on average, participants evidenced habituation of the NFR and sensitization of pain ratings. However, a substantial subgroup of participants exhibited the opposite pattern of change. In conditional models, behavioral inhibition, b = .10, P = .003, and behavioral activation, b = ?.07, P = .07, independently interacted with the growth curve to predict changes in NFR, but not pain ratings, across the 12 stimuli. These findings provide preliminary experimental support for Jensen and colleagues' 2-factor model of pain experience and implicate a role for approach and avoidance motivations in descending modulation of NFR.

Differential development of sensory hypersensitivity and a measure of spinal cord hyperexcitability following whiplash injury

Widespread sensory hypersensitivity is present in acute whiplash and is associated with poor recovery. Decreased nociceptive flexion reflex (NFR) thresholds (spinal cord hyperexcitability) are a feature of chronic whiplash but have not been investigated in the acute to chronic injury stage. This study compared the temporal development of sensory hypersensitivity and NFR responses from soon after injury to either recovery or to transition to chronicity. It also aimed to identify predictors of persistent spinal cord hyperexcitability. Pressure and cold pain thresholds, NFR responses (threshold and pain VAS) were prospectively measured in 62 participants at <3 weeks, 3 and 6 months post whiplash injury and in 22 healthy controls on two occasions a month apart. Pain levels and psychological distress (GHQ-28; IES) were measured at baseline. Whiplash participants were classified at 6 months post-injury using the Neck Disability Index: recovered (?8%), mild pain and disability (10–28%) or moderate/severe pain and disability (?30%). All whiplash groups demonstrated spinal cord hyperexcitability (lowered NFR thresholds) at 3 weeks post-injury. This hyperexcitability persisted in those with moderate/severe symptoms at 6 months but resolved in those who recovered or reported lesser symptoms at 6 months. In contrast generalized sensory hypersensitivity (pressure and cold) was only ever present in those with persistent moderate/severe symptoms and remained unchanged throughout the study period. This suggests different mechanisms underlie sensory hypersensitivity and NFR responses. In multivariate analyses only initial NDI scores (p = 0.003) were a unique predictor of persistent spinal cord hyperexcitability indicating possible ongoing peripheral nociception following whiplash injury.     

The Relationship Between Adverse Life Events and Endogenous Inhibition of Pain and Spinal Nociception: Findings From the Oklahoma Study of Native American Pain Risk (OK-SNAP)

Adverse life events (ALEs) are a risk factor for chronic pain; however, mechanisms underlying this association are not understood. This study examined whether cumulative ALE exposure impairs endogenous inhibition of pain (assessed from pain report) and spinal nociception (assessed from nociceptive flexion reflex; NFR) in healthy, pain-free Native Americans (n = 124) and non-Hispanic Whites (n = 129) during a conditioned pain modulation (CPM) task. Cumulative ALE exposure was assessed prior to testing by summing the number of potentially traumatic events experienced by each participant across their lifespan. Multilevel modeling found that ALEs were associated with NFR modulation during the CPM task even after controlling for general health, body mass index, sex, age, blood pressure, sleep quality, stimulation intensity, stimulus number, perceived stress, and psychological distress. Low exposure to ALEs was associated with NFR inhibition, whereas high exposure to ALEs was associated with NFR facilitation. By contrast, pain perception was inhibited during the CPM task regardless of the level of ALE exposure. Race/ethnicity did not moderate these results. Thus, ALEs may be pronociceptive for both Native Americans and non-Hispanic Whites by impairing descending inhibition of spinal nociception. This could contribute to a chronic pain risk phenotype involving latent spinal sensitization.PerspectiveThis study found that adverse life events were associated with impaired descending inhibition of spinal nociception in a sample of Native Americans and non-Hispanic Whites. These findings expand on previous research linking adversity to chronic pain risk by identifying a proximate physiological mechanism for this association.     

Neural correlates of a 'pessimistic' attitude when anticipating events of unknown emotional valence

Since we do not know what future holds for us, we prepare for expected emotional events in order to deal with a pleasant or threatening environment. From an evolutionary perspective, it makes sense to be particularly prepared for the worst-case scenario. We were interested to evaluate whether this assumption is reflected in the central nervous information processing associated with expecting visual stimuli of unknown emotional valence. While being scanned with functional magnetic resonance imaging, healthy subjects were cued to expect and then perceive visual stimuli with a known emotional valence as pleasant, unpleasant, and neutral, as well as stimuli of unknown valence that could have been either pleasant or unpleasant. While anticipating pictures of unknown valence, the activity of emotion processing brain areas was similar to activity associated with expecting unpleasant pictures, but there were no areas in which the activity was similar to the activity when expecting pleasant pictures. The activity of the revealed regions, including bilateral insula, right inferior frontal gyrus, medial thalamus, and red nucleus, further correlated with the individual ratings of mood: the worse the mood, the higher the activity. These areas are supposedly involved in a network for internal adaptation and preparation processes in order to act according to potential or certain unpleasant events. Their activity appears to reflect a 'pessimistic' bias by anticipating the events of unknown valence to be unpleasant.     

Augmentation of serotonin enhances pleasant and suppresses unpleasant cortical electrophysiological responses to visual emotional stimuli in humans

The serotonergic system is one of the major systems targeted in the pharmacological treatment of a wide range of mood disorders including depression; however, little is known about the neurophysiological mechanisms underlying the effects of serotonin (5-HT) on affective phenomena including emotional behaviours, mood and emotional processing. The aim of the current study was to investigate how 5-HT acutely modulates steady-state visually evoked potentials (SSVEP), heart rate (HR) and verbal ratings associated with the viewing of differently valent emotional images. In a randomised double-blind, placebo-controlled design, 17 healthy subjects were tested under two acute treatment conditions: placebo and citalopram (20 mg) (a selective serotonin re-uptake inhibitor, or SSRI). Participants were tested 2 h post treatment whilst viewing 75 images (categorised as pleasant, neutral or unpleasant). Results indicate that under placebo treatment, processing of unpleasant valence [unpleasant (-) neutral images] was associated with decreases in SSVEP amplitude and latency in frontal and occipital cortices, whereas processing of pleasant valence [pleasant (-) neutral images] was associated with amplitude decreases and latency increases within frontal and left temporoparietal cortices. Decreases in both amplitude and latency are both interpreted as surrogate measures of cortical activation or excitation. Citalopram relative to placebo attenuated the electrophysiological activation to unpleasant valence within frontal and occipital cortices, but potentiated electrophysiological activation (amplitude only) to pleasant valence within parietooccipital cortices. Citalopram relative to placebo also suppressed differences in heart rate associated with the viewing of pleasant and unpleasant images, but did not alter subject's subjective responses to emotional images. Results suggest that responsiveness to pleasant and unpleasant stimuli following neurochemical modulation may vary across different response systems (i.e. self-report, HR and SSVEP). Electrophysiological findings suggest that acute serotonergic augmentation with citalopram modulates cortical processing of emotionally valent stimuli such that response to pleasant valence is potentiated and response to unpleasant valence is suppressed. The findings suggest a possible neurophysiological mechanism underlying antidepressant drug action on emotion.     

The Relationship Between Experienced Discrimination and Pronociceptive Processes in Native Americans: Results From the Oklahoma Study of Native American Pain Risk

Native Americans (NAs) have higher pain rates than the general U.S. population. It has been found that increased central sensitization and reduced pain inhibition are pronociceptive processes that increase pain risk; yet, little attention has focused on the influence of psychosocial factors. Discrimination is a psychosocial factor associated with increased pain in other minoritized groups; however, it is unclear whether it also promotes pain in NAs. This study analyzed data from 269 healthy, pain-free participants (N = 134 non-Hispanic whites [NHWs], N = 135 NAs) from the Oklahoma Study of Native American Pain Risk. Experienced discrimination was measured using the Everyday Discrimination Scale (EDS). Nociceptive processes were measured via static measures of spinal sensitivity (nociceptive flexion reflex [NFR] threshold, 3-stimulation NFR threshold), temporal summation of pain (TS-Pain) and nociceptive flexion reflex (TS-NFR), and conditioned pain modulation of pain (CPM-Pain) and NFR (CPM-NFR). Results demonstrated that greater discrimination was associated with enhanced TS-NFR and impaired CPM-NFR but not static measures of spinal sensitivity or measures of pain modulation (TS-Pain, CPM-Pain). Although the effects of discrimination on outcomes were similar in both groups (not moderated by ethnicity), NAs experienced higher levels of discrimination and therefore discrimination mediated a relationship between ethnicity and impaired CPM-NFR. This indicates experienced discrimination may promote a pain risk phenotype in NAs that involves spinal sensitization resulting from impaired inhibition of spinal nociception without sensitization of pain experience.PerspectiveThis study found that discrimination was associated with spinal sensitization and impaired descending inhibition of spinal nociception. These findings bolster our understanding of how social stressors experienced disproportionately by minoritized groups can contribute to pain outcomes.     

Propranolol selectively blocks the enhanced parietal old/new effect during long-term recollection of unpleasant pictures: A high density ERP study

Evidence from both animal and human research suggests that the formation of emotional memories is triggered by the beta-adrenergic system. To confirm whether modulation of central beta-adrenergic transmission is specifically involved in the neural signature of memory performance, the pre-encoding effect of propranolol (80 mg) on event-related potentials (ERPs) was measured in a placebo-controlled, double-blind, parallel-group study in 46 male healthy subjects using high density EEG and source imaging analysis during encoding and retrieval (after 1 week) of IAPS pictures of unpleasant, neutral and pleasant contents; for recognition 90 old pictures were randomly mixed with 90 new pictures. During retrieval correctly remembered old pictures elicited a significantly larger positive voltage change over the centro-parietal cortex than new pictures. Propranolol significantly reduced this old/new difference of the mean ERP amplitudes (500–800 ms) for unpleasant but not for neutral and pleasant memories. This effect correlated with salivary alpha-amylase activity, a surrogate for central adrenergic stimulation. In conclusion, propranolol selectively blocked the neural signature of unpleasant memories by mechanisms in which the parietal cortex seems to be specifically involved.     

Effects of odors on pain perception: deciphering the roles of emotion and attention

Emotions have been shown to alter pain perception, but the underlying mechanism is unclear since emotions also affect attention, which itself changes nociceptive transmission. We manipulated independently direction of attention and emotional state, using tasks involving heat pain and pleasant and unpleasant odors. Shifts in attention between the thermal and olfactory modalities did not alter mood or anxiety. Yet, when subjects focused attention on the pain, they perceived it as clearly more intense and somewhat more unpleasant than when they attended to the odor. In contrast, odor valence altered mood, anxiety level, and pain unpleasantness, but did not change the perception of pain intensity. Pain unpleasantness ratings correlated with mood, but not with odor valence, suggesting that emotional changes underlie the selective modulation of pain affect. These results show that emotion and attention differentially alter pain perception and thus invoke at least partially separable neural modulatory circuits.