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OBJECTIVE To compare spatial pain modulation capabilities between adolescents with and without migraine. BACKGROUND Conditioned pain modulation (CPM) responses at the leg are similar in adolescents with versus without migraine. However, the anatomical region of testing may affect spatial pain modulation capabilities as differences in nociceptive processing between patients with migraine and healthy controls are found in local areas that are near the site of clinical pain but not in nonlocal areas. This study aimed to examine spatial pain modulation capabilities tested by the CPM paradigm using test stimulus applied to a local body area. METHODS Nineteen adolescents with migraine (age 14.9 ± 2.3, mean ± SD; 16 female) and 20 healthy adolescents (age 13.8 ± 2.5, mean ± SD; 16 female) completed this case-control study at Cincinnati Children's Hospital Medical Center. Pressure pain thresholds (PPT) were assessed at the trapezius before and during immersion of the foot in a cold water bath (8°C). RESULTS In the migraine group (146.0 ± 79.1, mean ± SD), compared to healthy controls (248.0 ± 145.5, mean ± SD), significantly lower PPT (kilopascal) values were found (estimate = 124.28, 95% CI: 58.98, 189.59, p

This case-control study examines if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents.Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Sleep is often disturbed in adolescents with migraine, and could contribute to the alterations in functional connectivity.Twenty adolescents with migraine and 20 healthy controls were recruited from Cincinnati Children's Hospital. Participants completed surveys about their headaches and overall sleep quality, sleep hygiene, and perceived sleep difficulties (Insomnia Severity Scale [ISI]); completed wrist-worn actigraphy; and underwent a magnetic resonance imaging scan.Adolescents with migraine differed from healthy controls only in perceived difficulty in sleep initiation and maintenance (ISI: 8.5 ± 4.7 and 4.5 ± 3.7 [mean ± standard deviation], -4.00 [95% confidence: -6.7 to -1.3], p = 0.005) and had greater functional connectivity between the amygdala and the posterior cingulate cortex, precuneus, dorsolateral prefrontal, sensorimotor, and the occipital cortexes. The differences in functional connectivity of the amygdala were not mediated by the subjective/objective sleep measures (ISI/wake minutes after sleep onset).Adolescents with migraine have greater connectivity between the amygdala and areas involved in sensory, affective, and cognitive aspects of pain. These alterations may not be due to higher levels of sleep difficulties in adolescents with migraine, suggesting that both amygdala and sleep alterations may play an independent role in migraine pathophysiology. This advances the understanding of the mechanisms underlying pediatric migraine and can potentially advance migraine management.

Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Considering that sleep is often disturbed in those adolescents with migrane, this study examined if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents. Twenty adolescents with migraine and 20 healthy controls completed surveys about their headaches and overall sleep quality, sleep hygiene and perceived sleep difficulties, wore a wrist-worn actigraphy, and underwent an MRI scan.Adolescents with migraine differed from healthy controls only in perceived sleep difficulties related to sleep initiation and maintenance (pPerspectiveThis article evaluates the role plays by sleep on neural alterations in adolescents with migraine. It indicates that neural alterations due to migraine are not related to alterations in subjective and actigraphic sleep difficulties. This advances the understanding of the mechanisms underlying pediatric migraine and can potentially advance migraine management.

Psychological factors, such as anxiety, depression, and pain catastrophizing, may affect how healthy individuals experience experimental pain. However, current literature puts forth contradictory results, possibly due to differing study methodologies, such as the type of psychophysical measure or survey. To better understand such results, this paper analyzed the relationships between psychological factors and experimental pain outcomes across eight different studies (total n= 595) conducted in different populations of healthy adult and adolescent participants. Analyses were conducted with and without controlling for sex, age, and race. Each study was analyzed separately and as part of an aggregate analysis. Even without correction for multiple comparisons, only a few significant relationships were found for the individual studies. Controlling for demographic factors had minimal effect on the results. Importantly, even the few statistically significant models showed relatively small effect sizes; psychological factors explained no more than 20% of the variability in experimental pain sensitivity of healthy individuals. The aggregate analyses revealed relationships between anxiety and PPT / cold pain ratings and between pain catastrophizing and PPT. Sample size calculations based on the aggregate analyses indicated that several hundred participants would be required to correctly detect relationships between these psychological factors and pain measures. These overall negative findings suggest that anxiety, depression, and pain catastrophizing in healthy individuals may not be meaningfully related to experimental pain outcomes. Furthermore, positive findings in the literature may be subject to small group effects and publication bias towards positive findings.

BACKGROUND. The assessment of alcohol consumption during a drinking bout, known as drinking topography, may help improve understanding of biopsychosocial mechanisms underlying alcohol consumption. However, past studies have been limited by effort-intensive, time-consuming, and error-prone processes involved in collecting, organizing, and standardizing drinking topography data. Recent technologies allowing integrated data collection and greater environmental control, such as virtual reality (VR), could resolve these problems. METHODS. In this pilot project, we assessed alcohol consumption topography of participants in a VR drinking environment with a programmable virtual confederate (i.e., bar goer) during two testing sessions. In one, the confederate drank quickly (30-60 second sip interval). In the other, the confederate drank slowly (60-120 second sip interval). Participants’ hands and beverage were represented in VR. Between sips, beverages were placed on a Bluetooth-enabled scale, allowing real-time updates of drink weight. Participant experience was assessed after each testing visit. Multilevel modeling was used to characterize the effect of confederation condition on sip interval and sip volume. Descriptive analyses were used for participant experience data. RESULTS. Results showed significant, moderate-to-strong between-visit correlations for topographic measures (r=.50 to r=.84) and indicate participants found the experience to be comfortable and acceptable. Multilevel models indicated participants had greater sip volumes and lower sip intervals when the confederate drank quickly. CONCLUSIONS. Future studies should take advantage of the considerable translational value of this technology to improve understanding of risk associated with individual drinking bouts and develop novel interventions for reducing hazardous drinking.

Cognitive behavioral therapy (CBT) is a psychological intervention that involves development of coping strategies to reduce the experience of pain. Although CBT is a promising intervention to reduce headache days in patients with migraine, it may not be effective for all patients. Thus, there is a need to identify markers that could predict which patients will respond to CBT. We aimed to determine whether baseline brain function and amygdalar connectivity, assessed by functional magnetic resonance imaging, or pain modulation capacities, assessed by the conditioned pain modulation (CPM) response, can predict a reduction in headache days after CBT in adolescents with migraine. Patients with migraine (n = 20; age range 10-17 years) completed 8 weekly CBT sessions. The CPM response was examined in the trapezius and the leg. Headache days significantly decreased after CBT (P < 0.001). Greater functional connectivity before CBT between the right amygdala and frontal gyrus, anterior cingulate cortex, and precentral gyrus was related to greater headache reduction after CBT. Greater reduction in headache days after CBT was related with less efficient CPM response before CBT at the trapezius (r = -0.492, P = 0.028) but not at the leg. This study found that headache reduction after CBT was related to right amygdala connectivity with frontal and sensorimotor regions at baseline as well as baseline pain modulation capacities. These findings suggest that individual differences in brain function and pain modulation can be associated with clinical improvements and help with determination of CBT responsiveness.

OBJECTIVES This basic mechanistic study examined the changes in brain activation and resting-state connectivity after 8 weeks of CBT in youth with migraine. BACKGROUND Cognitive behavioral therapy (CBT) is a psychological intervention that is effective in reducing pain in migraine patients. However, the neural mechanisms underlying CBT in adolescents with migraine are not yet known. METHODS Eighteen adolescents with migraine (15 females, age 15.1 ± 2.1 years [mean ± SD]) completed 8 weekly CBT sessions. Before the first and after the final CBT session, participants underwent structural and resting-state blood-oxygen-level-dependent contrast MRI scans. Arterial spin labeling was also used to examine brain activation during the resting state. For connectivity analyses, the right and left amygdala were chosen as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated. RESULTS Headache frequency decreased from 15 ± 7.4 headaches per month before CBT to 10 ± 7.4 after CBT (P

OBJECTIVE: Discrepancies between self-reported and actigraphy sleep measures are common, producing ambiguity about which are better predictors of experimental pain outcomes. The current study tested if pain intensity and situational pain catastrophizing following experimental pain were differentially predicted by self-reported or actigraphy sleep measures in patients with chronic temporomandibular disorder (TMJD) or healthy controls (HCs). METHODS: Forty patients with TMJD and 20 HCs completed self-report sleep measures (Pittsburgh Sleep Quality Index, PSQI; Insomnia Severity Index, ISI; PROMIS Sleep-Related Impairment [SRI] and Sleep Disruption [SD]), underwent an experimental pain induction consisting of four consecutive cold-water hand immersions, and provided pain intensity and situational pain catastrophizing ratings. Participants also wore an actigraphy watch and completed sleep diaries for seven days, which were averaged for actigraphic indices of total sleep time, sleep efficiency, wake after sleep onset, and self-reported sleep quality and restfulness. RESULTS: Individuals with TMJD reported higher pain intensity during experimental pain (M=65.81 vs. 47.77, p=.007) and self-reported worse sleep compared to HCs (all p’s< .02, Cohen’s D=0.73–1.25). No group differences emerged for actigraphy measures (all p’s> .05, Cohen’s D=0.05–0.53). Sleep variables did not interact with group to predict responses to experimental pain (all p’s>.05). Across groups, PROMIS-SRI predicted pain intensity (β=0.36, p=.008) and catastrophizing (β =0.36, p=.009) after controlling for multiple comparisons, smoking, medications, and age. CONCLUSION: Self-reported sleep (but not actigraphy) measures differentiate patients with TMJD from HCs. Sleep-related interference may place people at particular risk for higher pain intensity and catastrophizing following experimental pain.

Quantitative sensory testing (QST) is widely used to assess somatosensory function by application of controlled stimuli across a variety of modalities. The aim of the present meta-analysis is to synthesize QST results across a wide array of studies of patients with migraine to identify the QST parameters that are reliably different between patients with migraine and healthy controls. In addition, we aimed to determine whether such differences vary according to stimulus location. A comprehensive literature search (up to January 2017) was conducted, which included studies comparing QST parameters between patients with migraine and healthy controls. For each QST modality, we calculated up to 3 meta-analyses for combined (combined data from multiple testing locations), local (head and neck), and nonlocal (outside the head or neck) locations. A total of 65 studies were included in the meta-analyses. Lower heat and pressure pain thresholds were observed in patients with migraine compared with healthy controls in the combined locations. Importantly, lower pressure pain threshold in patients with migraine was found in local areas but not in nonlocal areas. In addition, patients with migraine had higher pain ratings to cold suprathreshold stimuli for combined and nonlocal areas, and higher pain ratings to electrical suprathreshold stimuli for nonlocal areas. This meta-analysis indicates that the alterations in nociceptive processing of patients with migraine may be modality, measure, and location specific. These results provide researchers and clinicians the evidence to choose QST parameters optimally suited for differentiating patients with migraine and healthy controls.

While perceived threat (anticipated harm) and challenge (test of abilities) have been previously found to predict pain intensity ratings to thermal stimuli in healthy populations, few studies have assessed the relationship between threat and challenge and experimental pain outcomes in patients with chronic pain. This study examined associations of perceived threat and challenge on quantitative sensory testing (QST) outcomes in patients with temporomandibular joint disorder (TMJD) and healthy controls. In the present study, 40 adults with TMJD (n = 35 female, mean age = 30.4, SD = 6.19) and 22 healthy controls (n = 18 female, mean age = 27.8, SD = 7.07) provided separate ratings of threat and challenge immediately prior to completing painful heat, pressure, and punctate QST. Participants provided ratings of pain intensity following each stimulus. In both patients with TMJD and healthy controls, challenge ratings correlated with ratings of thermal pain intensity (r= .30, p = .02), while ratings of both challenge and threat correlated with ratings of pressure and punctate pain intensity (r’s = .36 - .50, p’s .05). These results replicate and extend prior research by demonstrating that perceived threat and challenge of a QST procedure can predict pain outcomes in patients with chronic pain. Future research should explore relationships between perceptions of threat and challenge with other QST modalities (i.e., delayed-onset muscle pain, electric pain), and explore how perception of QST parameters may influence pain chronicity. Supported by NIDCRR00DE022368-03.