The Power of Belief: Expectation-driven and Placebo Modulation of Empathic Pain (PoB-EP)

This study investigates how belief and expectation influence empathic pain-the pain we feel when observing others in distress. Healthy adult participants will be randomly assigned to one of three groups: no-treatment control, placebo nasal spray, oxytocin-containing nasal spray. Participants in both the placebo and oxytocin conditions will be informed that they are receiving oxytocin, described as a potent agent for pain relief. During functional MRI scanning, all participants will view naturalistic pain-related videos and provide ratings of perceived subjective pain. The study aims to examine how cognitive beliefs and neuromodulatory interventions alter subjective pain experience and brain activity, including changes in brain network communication.

Study Overview

• Status: Recruiting
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Intranasal Oxytocin (OT) 24 IU; Drug: Intranasal placebo administration

Detailed Description

This study examines how belief-driven expectations modulate empathic pain at both behavioral and neural levels. Healthy adult participants will be randomly assigned to one of three groups: no-treatment control, placebo nasal spray, oxytocin-containing nasal spray. Participants in both the placebo and oxytocin conditions will be informed that they are receiving oxytocin, described as a potent agent for pain relief.

During fMRI scanning, participants will complete a naturalistic empathic pain task by viewing videos depicting others in pain and rating their perceived pain on a standardized scale. Behavioral data will be transformed into analgesia-weighted scores to capture individual sensitivity to expectation-driven analgesia. Neural data will include whole-brain voxel-wise activity, multivariate predictive patterns derived from partial least squares regression (PLSR), and directed functional connectivity assessed using lagged partial-correlation directionality analysis (LPC-DA) to evaluate top-down and bottom-up information flow.

The primary objectives are to (1) assess the behavioral effects of expectation-driven analgesia, (2) identify brain regions predictive of pain modulation, and (3) characterize hierarchical network reorganization under different interventions.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Weihua Zhao; Phone Number: +8618780247797; Email: zarazhao@uestc.edu.cn
• Study Contact Backup: Name: Keith Kendrick; Phone Number: +86-28-61830811; Email: k.kendrick.uestc@gmail.com

Study Locations

• China
  • Chengdu, China
    • Enrolling by invitation
    • University of Electronic Science and Technology of China
  • Sichuan
    • Chengdu, Sichuan, China, 611731
      • Recruiting
      • Weihua Zhao
      • Contact: Weihua Zhao, Phd; Phone Number: 18780247797; Email: zarazhao@uestc.edu.cn
      • Principal Investigator: Weihua Zhao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• (1) Healthy subjects without any past or present psychiatric or neurological disorders; (2) Healthy subjects without any current psychotherapeutic medication.

Exclusion Criteria:

• (1) Participant with any past or present psychiatric or neurological disorders; (2)Participant with any current psychotherapeutic medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intranasal Oxytocin; Administer oxytocin (24 IU) intranasally.	Drug: Intranasal Oxytocin (OT) 24 IU; Administer oxytocin (24 IU) intranasally, 6 individual 0.1 ml puffs (4 IU/0. 1ml), three puffs per nostril one every 30 seconds. The participants will be informed that they are receiving oxytocin, described as a potent agent for pain relief.; Other Names: Intranasal Oxytocin
No Intervention: Intranasal nothing (control); Control condition
Active Comparator: Intranasal placebo; Administer placebo intranasally.	Drug: Intranasal placebo administration; Administer placebo intranasally, 6 individual 0.1 ml puffs, three puffs per nostril one every 30 seconds. The participants will be informed that they are receiving oxytocin, described as a potent agent for pain relief.; Other Names: Intranasal placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analgesia-weighted empathic pain ratings (R')	Subjective pain ratings for each stimulus adjusted for treatment-specific baseline and analgesia-dependent gain to capture individual sensitivity to expectation-driven analgesia.	During fMRI scanning (45 minutes follollowing treament adminstration), for each video stimulus presentation
Whole-brain multivariate predictive patterns	Partial least squares regression (PLSR) will be applied to voxel-wise fMRI contrast maps to identify latent components that predict analgesia-weighted pain scores under different interventions.	During fMRI scanning (45 minutes follollowing treament adminstration), analyzed post-session
Directed functional connectivity and network hierarchy	Lagged partial-correlation directionality analysis (LPC-DA) among key regions identified by PLSR will quantify top-down and bottom-up information flow in empathic pain circuits.	During fMRI scanning (45 minutes follollowing treament adminstration), analyzed post-session

Collaborators and Investigators

• Sponsor: University of Electronic Science and Technology of China
• Investigators: Study Chair: Siying Wang, University of Electronic Science and Technology of China

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): February 20, 2026
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: December 26, 2025
• First Submitted That Met QC Criteria: January 18, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 18, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Oxytocin; fMRI; Placebo; Analgesic expectation; Empathic pain
• Other Study ID Numbers: UESTC-neuSCAN-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No