Neural and Psychological Mechanisms of Pain Perception
2 other identifiers
interventional
500
1 country
1
Brief Summary
Background: \- Painful stimuli cause changes in a network of brain regions called the "Pain Matrix." But most of these regions respond to many other stimuli, not just pain. Researchers want to understand how different factors influence pain. They want to test what happens when people expect different levels of pain and receive treatments that can modify pain. They want to see if these factors influence decisions about pain and how the body responds to it. They also want to compare pain with responses like taste and vision. Objectives: \- To better understand how pain and emotions are processed and influenced by psychological factors. Eligibility: \- Healthy volunteers ages 18-50. Design:
- This study requires 1 to 2 clinic visits that last 1 to 3 hours.
- Participants will be screened with medical history and physical exam.
- Some participants will have one or more magnetic resonance imaging (MRI) scans of their brain. For MRI, participants will lie on a table that slides in and out of a cylinder. The scanner makes loud knocking noises. They will get earplugs.
- Participants heart activity will be recorded with electrocardiogram. Their pulse, sweating, and breathing will be monitored.
- Some participants will take a taste test. Others may perform simple tasks. Others may receive pain in their arm, leg, or hand. The pain will come from heat or electric shocks. Others may judge pain using a topical pain-relieving cream. Some of these tests may be given during MRI.
- Participants will fill out questionnaires.
- The study will last 3 years.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable pain
Started Jun 2015
Longer than P75 for not_applicable pain
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 14, 2015
CompletedFirst Posted
Study publicly available on registry
May 18, 2015
CompletedStudy Start
First participant enrolled
June 11, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 20, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 20, 2027
March 9, 2026
January 5, 2026
11.7 years
May 14, 2015
March 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Physiological responses (heart rate, skin conductance, respiration, pupil dilation, eye gaze position)
In behavioral and fMRI experiments, we measure autonomic responses in anticipation and response to painful and non-painful stimuli using non-invasive measures.
During the study visit in response to painful and non-painful stimuli.
Pain perception (pain ratings)
Substudies of pain collect pain ratings using a visual analogue scale, either verbally or via computer.
During the study visit in response to painful stimuli.
BOLD response in brain regions of interest measured using fMRI
FMRI substudies proceed following behavioral substudies. We measure brain responses in anticipation and response to painful and non-painful stimuli.
During the study visit in response to painful and non-painful stimuli.
Secondary Outcomes (1)
Questionnaire measures (e.g. State-trait anxiety index, Fear of Pain questionnaire, Intolerance of Uncertainty questionnaire, McGill Pain Questionnaire)
Trait measures are collected during initial screening visit ; State measures are collected on every visit
Study Arms (8)
Substudy 1: Instructed subjects
OTHERParticipants are instructed about outcomes
Substudy 1: Uninstructed subjects
OTHERParticipants learn through experience
Substudy 2: heat group
OTHERParticipants learn about heat outcomes through conditioning
Substudy 2: salt group
OTHERParticipants learn about salt outcomes through conditioning
Substudy 2: sugar group
OTHERParticipants learn about sugar outcomes through conditioning
Substudy 3: healthy volunteers
NO INTERVENTIONAll participants experience all outcomes, within subjects designs
Substudy 4: healthy volunteers
OTHERParticipants are instructed to attend toward or away from the stimulus
Substudy 5: healthy volunteers
OTHERParticipants experience both placebo and cue-based expectations within subjects
Interventions
In sub-study 1, half the participants are instructed about outcomes, half learn through experience.
In sub-study 4, participants learn about outcomes and we manipulate attention toward or away from the pain.
In sub-studies 2 and 3, participants are exposed to thermal stimuli and/or tastants (sugar water, salt water, neutral rinse) and we are measuring how learning varies based on the type of outcome.
In sub-study 5, we test whether placebo effects and expectancy cues modulate pain through similar mechanisms.
Eligibility Criteria
You may qualify if:
- Healthy
- Between 18 and 50 years old
- Fluent in English
- Able to provide written informed consent.
You may not qualify if:
- Unable to comply with study procedures or follow-up visits.
- Has a major medical condition or medical history that in a clinician's assessment could affect heat sensitivity, pain thresholds, or ability to comply with study procedures. This may include cardiovascular, autonomic, or neurological conditions, including stroke, blindness, deafness, a history of brain damage, or a chronic systemic disease (e.g., diabetes).
- Has a current mood disorder, anxiety disorder, or substance use disorder, or has a history of psychosis, hospitalization for a mental health condition, or recurrent psychiatric episodes.
- Has a medical condition that in a clinician's assessment might affect somatosensation (e.g., Raynaud s disease, peripheral neuropathy, or circulatory disorder).
- Has a current chronic pain condition or has had chronic pain in the past (painful condition lasting more than six months).
- Has a dermatological condition affecting the testing region such as scars, burns, or recent tattoos that might influence cutaneous sensibility.
- Regular use of prescription medication that has a significant effect on pain or heat perception. Excluded medications include central-acting agents such as opiates (morphine, tramadol), antidepressants (amitriptyline, duloxetine, milnacipran), anticonvulsants (gabapentin, pregabalin), anxiolytics (barbituates, benzodiazepines), hypnotics (zolpidem, sodium oxybate), antipsychotics (valproate, lithium, olanzapine), antimigraine agents (sumatriptan, ergotamine), and muscle relaxants (cyclobenzaprine, carisoprodol). Use of analgesic medications, such as non-steroidal anti-inflammatories, salicylates, and acetaminophen, taken on an "as needed" basis is acceptable as long as the last dose taken was within 5 half-lives of testing.
- Is pregnant.
- NIH staff member who is a subordinate/relative/co-worker of any investigator on the protocol.
- Individuals with conditions that could pose a risk relating to the safety of the fMRI procedure or pain stimulation will be excluded from the MRI portion of the protocol, but may participate in the non-fMRI sessions (with the exception of pregnant women). Such conditions include:
- Those with ferromagnetic metal in the cranial cavity or eye, e.g. aneurysm clip, implanted neural stimulator, cochlear implant, ocular foreign body.
- Those with an abnormality on a structural MRI.
- Those with an implanted cardiac pacemaker or auto-defibrillator.
- Those with an insulin pump.
- Those with irremovable body piercing.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (2)
Necka EA, Akintola T, Yu Q, Amir CM, Oretsky O, Atlas LY. Isolating Brain Mechanisms of Expectancy Effects on Pain: Cue-Based Stimulus Expectancies versus Placebo-Based Treatment Expectancies. J Neurosci. 2025 Aug 20;45(34):e0050252025. doi: 10.1523/JNEUROSCI.0050-25.2025.
PMID: 40721322DERIVEDAtlas LY, Dildine TC, Palacios-Barrios EE, Yu Q, Reynolds RC, Banker LA, Grant SS, Pine DS. Instructions and experiential learning have similar impacts on pain and pain-related brain responses but produce dissociations in value-based reversal learning. Elife. 2022 Nov 1;11:e73353. doi: 10.7554/eLife.73353.
PMID: 36317867DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lauren Y Atlas, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, OUTCOMES ASSESSOR
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 14, 2015
First Posted
May 18, 2015
Study Start
June 11, 2015
Primary Completion (Estimated)
February 20, 2027
Study Completion (Estimated)
February 20, 2027
Last Updated
March 9, 2026
Record last verified: 2026-01-05
Data Sharing
- IPD Sharing
- Will not share
We will share deidentified data only as per language in the protocol.