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Lasmiditan (LY573144/COL-144) is a high-affinity, centrally penetrant, selective 5-HT receptor agonist currently under investigation for acute treatment of migraine. Although lasmiditan is not known to induce vasoconstriction, it remains important to understand its effect on cardiovascular parameters because it is likely to be coadministered with β-adrenergic receptor antagonists used for migraine prophylaxis, such as propranolol. This phase 1, single-center, open-label, fixed-sequence study evaluated the cardiovascular and pharmacokinetic effects of 200 mg lasmiditan in 44 healthy subjects receiving repeated oral doses of twice-daily 80 mg propranolol under fasting conditions. Coadministration caused statistically significant decreases in mean hourly heart rate relative to propranolol alone, but the maximum magnitude of this effect was -6.5 bpm and recovered to predose levels by 3 to 4 hours before stabilizing. Additionally, short-lived (≤2.5 hours) statistically significant increases in systolic blood pressure (8.3 mm Hg) and diastolic blood pressure (6.4 mm Hg) were observed following coadministration. Consistent with the largely nonoverlapping metabolic pathways of lasmiditan and propranolol, exposure to either drug was not affected by coadministration. Overall, compared with administration of either drug alone, coadministration was generally well tolerated.
Learn More >Offset analgesia (OA), a large reduction in pain after a brief increase in intensity of an otherwise stable painful stimulus, has been established by a large body of research. But the opposite effect, onset hyperalgesia (OH), a disproportional hyperalgesic response after a briefly decreased intensity of a painful stimulus, has only been investigated in one previous study.
Learn More >Engaging in altruistic behaviors is costly, but it contributes to the health and well-being of the performer of such behaviors. The present research offers a take on how this paradox can be understood. Across 2 pilot studies and 3 experiments, we showed a pain-relieving effect of performing altruistic behaviors. Acting altruistically relieved not only acutely induced physical pain among healthy adults but also chronic pain among cancer patients. Using functional MRI, we found that after individuals performed altruistic actions brain activity in the dorsal anterior cingulate cortex and bilateral insula in response to a painful shock was significantly reduced. This reduced pain-induced activation in the right insula was mediated by the neural activity in the ventral medial prefrontal cortex (VMPFC), while the activation of the VMPFC was positively correlated with the performer's experienced meaningfulness from his or her altruistic behavior. Our findings suggest that incurring personal costs to help others may buffer the performers from unpleasant conditions.
Learn More >To investigate pain sensitivity in the masseter muscle and index finger in response to acute psychologic stress in healthy participants.
Learn More >Naltrexone reversibly blocks the effects of opioids and has been shown to decrease placebo analgesia. However, it is not clear (1) to what extent naltrexone affects pain modulation in a nontreatment context, for example, in response to pain cues or (2) how naltrexone given prior to pain-cue learning shapes pain responses. In a double-blind procedure prior to pain-cue conditioning, 30 healthy participants were randomized to receive an oral dose of naltrexone (50 mg) or inert pill. During functional magnetic resonance imaging, high and low pain pressures were paired with two different visual cues: a high pain cue and a low pain cue (learning sequence). During a test sequence, medium levels of pressure were used for both cues and the difference in subjective pain ratings following high and low pain cues was calculated. Results showed significant conditioned pain responses across groups (<.001); however, no significant difference between participants receiving naltrexone or inert pill (=.193). There was a significant correlation between the difference in high and low pain ratings during the learning sequence and the effect of high and low pain cues during the test sequence (r = .575, =.002). Functional magnetic resonance imaging analyses revealed no significant difference in brain activation between groups. Here, we demonstrate comparable learning of pain responses in participants treated with naltrexone or inert pill. The results point to the possibility that associative learning, and conditional responding to pain cues, is not dependent on endogenous opioids. Our results, using pain-cue conditioning to create reduced pain responses, contrast previous studies where opioid antagonists significantly reduced the placebo effect in treatment of pain.
Learn More >To compare somatosensory function profiles and psychologic factors in patients with primary burning mouth syndrome (BMS) and healthy controls and to evaluate correlations of subjective pain ratings with somatosensory and psychologic parameters.
Learn More >This study aims to (1) examine the temporal influence of peer victimization on mood, sleep quality, pain, and activity limitations in clinical and community samples of youth, and (2) test mood and sleep as mediators of peer victimization-pain pathways. One hundred fifty-six adolescents (n=74 chronic pain group) completed a week of online diary monitoring assessing their daily peer victimization experiences, negative mood, sleep quality, pain intensity, and pain-related activity limitations. In multilevel models controlling for group status, person-mean peer victimization (averaged across days) significantly predicted worse mood, pain, and activity limitations (all ps < .01) while daily victimization predicted worse mood (p < .05). Results from within-person mediation indicated a significant indirect effect of daily peer victimization on next-day activity limitations, through daily negative mood. Results from between-person mediation indicated that negative mood significantly mediated the relation between peer victimization and pain and the relation between peer victimization and activity limitations. Peer victimization is associated with negative health indicators in clinical and community samples of youth and may exert its influence on pain and pain-related activity limitations through negative mood. PERSPECTIVE: This article examines the temporal influence of peer victimization on pain in adolescents with and without chronic pain, and examines mood and sleep quality as mechanisms linking victimization to pain. This information may be useful for pain prevention researchers as well as providers who assess and treat pain in childhood.
Learn More >Fibromyalgia is a syndrome characterized by chronic widespread pain, with a multifactorial etiopathogenesis and high incidence of neuropsychiatric comorbidity. It has been inaccurately considered a pathological condition affecting only middle-aged women. The study aimed to explore the association of sociodemographic and clinical factors in patients with fibromyalgia with depression and/or anxiety. The present study is an analysis of a cross-sectional study of a secondary source. The prevalence ratio (PR) between the demographic and clinical variables of patients with fibromyalgia and concomitant depression and/or anxiety was calculated. Overall, 1,106 medical records were obtained with a confirmed diagnosis of fibromyalgia between 2010 and 2016; of these, 318 (28.75%) patients had an associated diagnosis of depression and/or anxiety. Approximately 28% women (295 of 1,052) and 42.6% men (23 of 54) suffered from depression and/or anxiety. In the adjusted explanatory model of depression and/or anxiety in patients with fibromyalgia, the relationship between sex (female PR = 0.5 [0.28-0.86]) and low socioeconomic strata (PR = 0.53 [0.33-0.70]) remained constant. In the study population, patients with fibromyalgia belonging to lower social strata were less likely to present with depression and anxiety. The male sex may pose as a risk factor for depression and/or anxiety in patients with fibromyalgia. Fibromyalgia has a huge impact on men's physical as well as mental health.
Learn More >We explored the ongoing question of whether placebo analgesia alters afferent nociceptive processing in a novel paradigm designed to minimize the role of response bias in placebo measurement. First, healthy adult participants received a standard heat placebo induction and conditioning procedure using a topical "analgesic" cream applied to one arm. During a subsequent placebo testing procedure, participants rated stimuli on the placebo-treated arm and untreated arm, using a task that minimized subjects' ability to guess the expected response, thus reducing experimenter demand. Retrospectively participants reported moderate analgesia effectiveness (mean=5.3/10), but for individual temperature ratings, only 2 subjects exhibited a perceptual placebo response >5 points. Next, these subjects completed a novel, exploratory task designed to measure changes in inter-arm in discriminative accuracy that would be expected from changes in afferent nociception. Both placebo responders (but no non-responders) showed reduced discriminative ability when the hotter stimulus occurred on the placebo arm, an effect consistent with alterations in nociceptive afferent flow and unlikely to be caused by response bias.
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