# Neural correlates of hypoalgesia driven by observation

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $765,487

## Abstract

Project Summary
Placebo effects held an ambivalent place in health care for at least two centuries. On the one hand, placebos
are traditionally used as controls in clinical trials to correct for biases and the placebo response is viewed as an
effect to be factored out in order to isolate and accurately measure the effects of the treatment. On the other
hand, there is scientific evidence that placebo effects represent fascinating psychoneurobiological events
involving the contribution of distinct central nervous as well as peripheral physiological mechanisms that
influence pain perception and clinical pain symptoms and substantially modulate the response to pain
therapeutics. Therefore, placebo effects have shifted from being a challenge for clinical trials to a resource to
trigger the reduction of pain based on endogenous mechanisms that can be activated in the brain to promote
hypolagesia, self-healing, and well-being. This is relevant in acute pain settings given that chronic opioid users
die within approximately 2.5 years of being prescribed their first opioid medication to treat acute pain.
Namely, analgesic effects can also occur without formal conditioning and direct prior experience because
crucial information necessary to build up expectations of analgesia can be acquired through observation of a
therapeutic benefit in others. Placebo analgesic effects following the observation of a benefit in another person
are similar in magnitude to those induced by directly experiencing an analgesic benefit. These observations
emphasize that contextual cues substantially modulate the individual placebo analgesic effects.
In this project, we propose a compelling research agenda to explore the neural mechanisms of hypoalgesia
driven by observation as a foundation for future development of novel nonpharmacological pain therapies
using pharmacological functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and
combined EEG/fMRI. It builds on a decade of experience in placebo research in PI Colloca’s lab and with
University of Maryland collaborators experienced in brain mapping and pain research. In Aim 1, we will
determine the role of endogenous opioids on the neural mechanisms of observationally-induced hypoalgesia
by using the opioid antagonist naloxone in a functional Magnetic Resonance Imaging (fMRI) setting. In Aim 2,
we will identify the impact of empathy by exploring how being in the immersive environment can enhance
observationally-induced analgesia. In Aim 3, we leverage the EEG/fMRI to determine the neural EEG/fMRI
transient changes that could co-occur when socially-induced expectations are violated.
The proposed research will generate mechanistic research that can be directly exploited to develop easily
implementable therapeutic strategies such video clips and virtual reality tools for acute pain management.

## Key facts

- **NIH application ID:** 9994837
- **Project number:** 5R01AT010333-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Luana Colloca
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $765,487
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994837

## Citation

> US National Institutes of Health, RePORTER application 9994837, Neural correlates of hypoalgesia driven by observation (5R01AT010333-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9994837. Licensed CC0.

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