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Pain modulation by intranasal oxytocin and emotional picture viewing - a randomized double-blind fMRI study.

ABSTRACT: The hormone oxytocin has been hypothesized to influence the emotional dimension of pain. This randomized, placebo-controlled, double-blind, crossover study explored whether intranasal oxytocin and emotional context can affect heat pain perception in 30 healthy male volunteers. After receiving 36 IU oxytocin or placebo, participants underwent functional Magnetic Resonance Imaging (fMRI) during which noxious and non-noxious thermode heat stimuli were applied. Simultaneously, scenes from the International Affective Pictures System (IAPS) with positive, neutral, and negative emotional valence were shown. Heat intensity and unpleasantness ratings were obtained. The activity of whole-brain correlates of heat processing was quantified via multi-voxel pattern analysis. We observed no appreciable main effects of oxytocin on ratings or neural pain correlates. Effects of emotional picture valence on ratings were smaller than reported in previous studies. Nevertheless, oxytocin was found to significantly enhance the influence of picture valence on unpleasantness ratings at noxious heat levels. No corresponding changes in whole-brain correlates of heat intensity processing were found. Our study provides evidence that intranasal oxytocin increases the effects of emotional context on the subjective unpleasantness of experimental heat pain. Future studies are needed to determine whether this effect can be utilized in clinical settings.

SUBMITTER: Zunhammer M

PROVIDER: S-EPMC4992880 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Pain modulation by intranasal oxytocin and emotional picture viewing - a randomized double-blind fMRI study.

Zunhammer Matthias M Geis Sandra S Busch Volker V Eichhammer Peter P Greenlee Mark W MW

Scientific reports 20160822

The hormone oxytocin has been hypothesized to influence the emotional dimension of pain. This randomized, placebo-controlled, double-blind, crossover study explored whether intranasal oxytocin and emotional context can affect heat pain perception in 30 healthy male volunteers. After receiving 36 IU oxytocin or placebo, participants underwent functional Magnetic Resonance Imaging (fMRI) during which noxious and non-noxious thermode heat stimuli were applied. Simultaneously, scenes from the Intern ...[more]

PMID: 27546446

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Project description:BACKGROUND:Emotional dysregulation and impaired attachment are potential contributors to the development of psychopathology in adolescence. This raises the question of whether oxytocin (OT), the paradigmatic "attachment hormone," may be beneficial in such contexts. Recent evidence suggests that intranasal administration of OT increases affiliative behavior, including trust and empathy. OT may also facilitate social reciprocity by attenuating the stress response to interpersonal conflict. To date, few studies have investigated the effects of intranasal oxytocin (IN-OT) on neurophysiological emotion regulation strategies in healthy adolescents, particularly during parent-adolescent interaction. To understand these mechanisms, our study will examine the effects of IN-OT on emotion regulation in adolescents during parent-adolescent stressful interactions, and on each adolescent's visual and neurophysiological strategies when visualizing attachment-related pictures. We hypothesize that IN-OT will influence psychophysiological outcomes under conditions of stress. We predict that IN-OT will momentarily increase feelings of safety and attenuate stress and hostile behavior during conflict situations. OT may also enhance attachment security by increasing comfort and proximity-seeking, and reducing neurophysiological hyperactivation. OBJECTIVE:The objective of this study is to evaluate the effects of IN-OT on insecure adolescents by studying their behavior and discourse during a disagreement with one of their parents. Their neurophysiological responses to pictures eliciting attachment-related emotions and their visual exploration strategies will also be investigated. METHODS:In this randomized, double-blind, placebo-controlled parallel-group design, 60 healthy male adolescents classified as insecurely attached will receive 24 international units (IU) of IN-OT versus placebo (PB), 45 minutes before the experimental tasks. Each adolescent will then be invited to engage in an experimental conflict discussion with one of his parents. The conflict session will be videotaped and coded for verbal and non-verbal interaction behavior, using the Goal-Corrected Partnership in Adolescence Coding System (GPACS). Each adolescent will then be asked to visualize attachment-related pictures on a screen. Eye-tracking (ET) and neurophysiological responses, including electrodermal activity (EDA) and heart rate (HR), will be recorded simultaneously and continuously during attachment-related picture viewing (Besançon Affective Picture Set-Adolescents, BAPS-Ado). RESULTS:Enrollment for the study was completed in May 2016. Data analysis commenced in July 2016. Study results will be submitted for publication in the winter of 2017. CONCLUSIONS:OT is a complex molecule with many facets that are not yet fully understood. This experimental protocol will increase scientific and clinical knowledge of emotion regulation skills in insecure adolescents by assessing the impact of IN-OT on parent-adolescent interaction and on the visual processing of attachment-related emotions. Positive results could lead to therapeutic uses of IN-OT to treat emotion dysregulation in adolescence.

Project description:BackgroundIntravenous morphine (IVM) is the most common strong analgesic used in trauma, but is associated with a clear time limitation related to the need to obtain an access route. The intranasal (IN) route provides easy administration with a fast peak action time due to high vascularization and the absence of first-pass metabolism. We aimed to determine whether IN sufentanil (INS) for patients presenting to an emergency department with acute severe traumatic pain results in a reduction in pain intensity non-inferior to IVM.Methods and findingsIn a prospective, randomized, multicenter non-inferiority trial conducted in the emergency departments of 6 hospitals across France, patients were randomized 1:1 to INS titration (0.3 μg/kg and additional doses of 0.15 μg/kg at 10 minutes and 20 minutes if numerical pain rating scale [NRS] > 3) and intravenous placebo, or to IVM (0.1 mg/kg and additional doses of 0.05 mg/kg at 10 minutes and 20 minutes if NRS > 3) and IN placebo. Patients, clinical staff, and research staff were blinded to the treatment allocation. The primary endpoint was the total decrease on NRS at 30 minutes after first administration. The prespecified non-inferiority margin was -1.3 on the NRS. The primary outcome was analyzed per protocol. Adverse events were prospectively recorded during 4 hours. Among the 194 patients enrolled in the emergency department cohort between November 4, 2013, and April 10, 2016, 157 were randomized, and the protocol was correctly administered in 136 (69 IVM group, 67 INS group, per protocol population, 76% men, median age 40 [IQR 29 to 54] years). The mean difference between NRS at first administration and NRS at 30 minutes was -4.1 (97.5% CI -4.6 to -3.6) in the IVM group and -5.2 (97.5% CI -5.7 to -4.6) in the INS group. Non-inferiority was demonstrated (p < 0.001 with 1-sided mean-equivalence t test), as the lower 97.5% confidence interval of 0.29 (97.5% CI 0.29 to 1.93) was above the prespecified margin of -1.3. INS was superior to IVM (intention to treat analysis: p = 0.034), but without a clinically significant difference in mean NRS between groups. Six severe adverse events were observed in the INS group and 2 in the IVM group (number needed to harm: 17), including an apparent imbalance for hypoxemia (3 in the INS group versus 1 in the IVM group) and for bradypnea (2 in the INS group versus 0 in the IVM group). The main limitation of the study was that the choice of concomitant analgesics, when they were used, was left to the discretion of the physician in charge, and co-analgesia was more often used in the IVM group. Moreover, the size of the study did not allow us to conclude with certainty about the safety of INS in emergency settings.ConclusionsWe confirm the non-inferiority of INS compared to IVM for pain reduction at 30 minutes after administration in patients with severe traumatic pain presenting to an emergency department. The IN route, with no need to obtain a venous route, may allow early and effective analgesia in emergency settings and in difficult situations. Confirmation of the safety profile of INS will require further larger studies.Trial registrationClinicalTrials.gov NCT02095366. EudraCT 2013-001665-16.

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Pain modulation by intranasal oxytocin and emotional picture viewing - a randomized double-blind fMRI study.

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Pain modulation by intranasal oxytocin and emotional picture viewing - a randomized double-blind fMRI study.

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