Impairment of Inhibition of Trigeminal Nociception via Conditioned Pain Modulation in Persons with Migraine Headaches.

OBJECTIVE: To assess conditioned pain modulation efficiency in persons with and without migraine headaches. DESIGN: Cross-sectional assessment of experimental pain. SETTING: University campus and surrounding community in a large Midwestern US city. SUBJECTS: Twenty-three adults with and 32 without a history of migraine headaches participated in the study. Participants were mostly female (N = 40) with an average age of 23 years. METHODS: Four electrocutaneous stimulations of the supraorbital branch of the left trigeminal nerve were delivered at 150% of an individually determined pain threshold. Conditioned pain modulation was assessed by applying a noxious counterstimulus (forearm ischemia) and delivering four more electrocutaneous stimulations. After each stimulation, pain and the nociceptive blink reflex were assessed. Depression and pain catastrophizing were assessed to control for the potential influence of these variables on pain modulation. RESULTS: Participants with and without migraine headaches had similar baseline pain responsivity, without significant differences in pain report or nociceptive blink reflexes. Pain report was inhibited by conditioned pain modulation in both the migraine and control groups. However, unlike nonmigraine controls, participants with migraines did not exhibit an inhibition of nociceptive blink reflexes during the ischemia task. This pattern persisted after controlling for level of pain catastrophizing and depression. CONCLUSIONS: Migraine sufferers exhibited impaired conditioned pain modulation of the nociceptive blink reflex, suggesting a deficiency in inhibition of trigeminal nociception, which may contribute to the development of migraine headaches.

Physiological predictors of response to exposure, relaxation, and rescripting therapy for chronic nightmares in a randomized clinical trial.

STUDY OBJECTIVES: Evidence supports the use of cognitive behavioral therapies for nightmares in trauma-exposed individuals. This randomized clinical trial replicated a study of exposure, relaxation, and rescripting therapy(ERRT) and extended prior research by including broad measures of mental health difficulties, self-reported physical health problems, and quality of life. Additionally, physiological correlates of treatment-related change assessed from a script-driven imagery paradigm were examined. METHODS: Forty-seven individuals were randomized to treatment or waitlist control. RESULTS: The treatment group demonstrated improvements relative to the control group at the one-week post-treatment assessment. At the 6-month follow-up assessment, significant improvements were found for frequency and severity of nightmares, posttraumatic stress disorder symptoms, depression, sleep quality and quantity, physical health symptoms, anger, dissociation, and tension reduction behaviors. Participants also reported improved quality of life. Treatment-related decreases in heart rate to nightmare imagery were correlated with improvements in sleep quality and quantity; treatment-related decreases in skin conductance to nightmare imagery were correlated with improvements in nightmare severity, posttraumatic stress disorder symptom severity, sleep quality, and fear of sleep; and treatment-related decreases in corrugator activity to nightmare imagery were correlated with improved physical health. CONCLUSIONS: Findings provide additional support for the use of ERRT in treating nightmares and related difficulties and improving sleep.

Are there sex differences in affective modulation of spinal nociception and pain?

UNLABELLED: 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. PERSPECTIVE: Evidence suggests that women are more sensitive to experimental and clinical pain, but the mechanisms contributing to these sex differences are poorly understood. Affective processes are known to play a role in regulating pain signaling and pain experience; therefore, the present study examined whether sex differences in affective experience contribute to sex differences in pain. Results indicate that in healthy individuals affective processes may not contribute to sex differences in pain.

Cognitive-behavioral treatment for chronic nightmares in trauma-exposed persons: assessing physiological reactions to nightmare-related fear.

Cognitive-behavioral treatments (CBTs) that target nightmares are efficacious for ameliorating self-reported sleep problems and psychological distress. However, it is important to determine whether these treatments influence objective markers of nightmare-related fear, because fear and concomitant physiological responses could promote nightmare chronicity and sleep disturbance. This randomized, controlled study (N=40) assessed physiological (skin conductance, heart rate, facial electromyogram) and subjective (displeasure, fear, anger, sadness, arousal) reactions to personally relevant nightmare imagery intended to evoke nightmare-related fear. Physiological assessments were conducted at pretreatment as well as 1-week, 3-months, and 6-months posttreatment. Results of mixed effects analysis of variance models suggested treatment reduced physiological and subjective reactions to nightmare imagery, gains that were generally maintained at the 6-month follow-up. Potential implications are discussed.

Does pain catastrophizing moderate the relationship between spinal nociceptive processes and pain sensitivity?

UNLABELLED: Existing evidence indicates that pain catastrophizing is associated with enhanced pain reports and lower pain threshold/tolerance levels, but is not significantly related to nociceptive flexion reflex (NFR) threshold in healthy and clinical pain samples. This suggests pain catastrophizing may modulate pain threshold at a supraspinal level without influencing descending modulation of spinal nociceptive inputs. To examine this issue further, the present study assessed NFR threshold, electrocutaneous pain threshold, and electrocutaneous pain tolerance, as well as subjective ratings of noxious stimuli in a sample of 105 healthy adults. Pain catastrophizing was assessed prior to testing using traditional instructions and after pain testing with instructions to report on cognitions during testing (situation-specific catastrophizing). As expected, NFR threshold was correlated with pain sensitivity measures, but uncorrelated with both measures of catastrophizing. Although situation-specific catastrophizing was correlated with some pain outcomes, neither catastrophizing measure (traditional or situation specific) moderated the relationship between NFR and pain sensitivity. These findings confirm and extend existing evidence that catastrophizing influences pain reports through supraspinal mechanisms (eg, memory, report bias, attention) without altering transmission of spinal nociceptive signals. PERSPECTIVE: Assessing catastrophic thoughts related to a specific painful event (situation-specific catastrophizing) provides important additional information regarding the negative cognitions that influence pain-related processes. However, neither situation-specific nor traditionally measured pain catastrophizing appear to enhance pain by engaging descending controls to influence spinal nociceptive processes.

Psychophysiological responses to pain: further validation of the nociceptive flexion reflex (NFR) as a measure of nociception using multilevel modeling.

Physiological reactions to noxious stimuli are often used to make inferences about pain, but few studies have thoroughly examined the intra- and interindividual relationships between them. In the present study (N=104), multilevel analyses was used to assess relations between physiological (nociceptive flexion reflex magnitude [NFR], blink reflex magnitude, skin conductance response [SCR], heart rate [HR]) and subjective reactions to electrocutaneous stimuli. All physiological reactions were significant predictors of ratings when entered alone, explaining 1% (SCR) to 29% (NFR) of the variance; but only NFR, blink, and HR were significant in a multivariate predictor model. Significant interindividual variability in slopes was found for blink and HR, but not NFR. A final trimmed model that included NFR, blink, and the blink random slope explained 35% of the variance in ratings.

Physiological-emotional reactivity to nightmare-related imagery in trauma-exposed persons with chronic nightmares.

Script-driven imagery was used to assess nightmare imagery-evoked physiological-emotional reactivity (heart rate, skin conductance, facial electromyogram, subjective ratings) in trauma-exposed persons suffering from chronic nightmares. Goals were to determine the efficacy of nightmare imagery to evoke physiological-emotional reactivity, correlates (mental health, nightmare characteristics) of reactivity, and consequences (sleep and health problems) of reactivity. Nightmare imagery resulted in significant reactivity relative to control imagery. No mental health variable (posttraumatic stress disorder status, depressive symptoms, dissociation) or nightmare characteristic (months experienced, frequency, similarity to trauma) was associated with reactivity level. However, nightmare imagery-evoked autonomic responses were associated with greater sleep disturbance and reported health symptoms, even when nightmare frequency was controlled. These results suggest nightmare-related autonomic reactions may contribute to sleep and health disturbance.

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.

Affective modulation of autonomic reactions to noxious stimulation.

Research suggests that emotion modulates spinal nociception and pain; however, there is limited evidence that other objective, nociceptive reactions are modulated. This study examined the impact of affective picture-viewing on autonomic reactions (skin conductance response, heart rate acceleration) resulting from noxious electric stimulations to the sural nerve. Pictures varying in affective valence (unpleasant, neutral, pleasant) were presented during which noxious stimulations were delivered. Skin conductance response and short-latency heart rate acceleration following each stimulation was calculated and averaged by picture valence. Results suggested that autonomic reactions were modulated in parallel. Specifically, reactions were smaller during pleasant pictures than unpleasant pictures, although unpleasant pictures did not result in significant facilitation relative to neutral pictures. The valence linear trend explained 26% of the variance in the multivariate combination of the reactions, suggesting emotion does modulate autonomic reactions to nociception. These results suggest that SCR and HR acceleration are outcomes that can be assessed together with NFR and pain report during picture-viewing to study affective modulation of spinal (NFR), supraspinal (SCR, HR acceleration), and subjective (pain report) nociceptive reactions.

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 modulation of nociception at spinal and supraspinal levels.

This study was designed to examine the effect of emotion on the nociceptive flexion reflex and pain ratings. To do so, 28 participants viewed pictures varying in emotional valence (unpleasant, neutral, pleasant) and electric stimulations were delivered during and in between pictures. Biceps femoris EMG resulting from the stimulations was used to quantify the nociceptive flexion reflex (spinal nociception), and pain ratings to the stimulations were used as an evaluative measure of supraspinal nociception. Manipulation checks suggested that pictures effectively manipulated emotion. Moreover, nociceptive flexion reflex magnitudes and pain ratings were modulated in a parallel manner. Specifically, viewing unpleasant pictures enhanced the nociceptive flexion reflex and pain, whereas viewing pleasant pictures inhibited the reflex and pain. Analyses suggested that emotional valence, but not arousal, mediated the effects of pictures.