Recruiting

Observational Study

Sponsor:

National Center for Complementary and Integrative Health (NCCIH)

Code:

NCT02446262

Conditions

Pain

Normal Physiology

Healthy Volunteers

Eligibility Criteria

Sex: All

Age: 18 - 50

Healthy Volunteers: Accepted

Interventions

Instructions

Attention

Thermal Pain

Placebo instructions

Study Details

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.

Conditions

Pain

Normal Physiology

Healthy Volunteers

Study ID

NCT02446262

Start date

Jun 11, 2015

Status verified date

Aug 31, 2026

Completion date

Feb 20, 2027

Anticipated

Primary completion date

Feb 20, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 50

Healthy Volunteers: Accepted

  • INCLUSION CRITERIA:
  • Healthy
  • Between 18 and 50 years old
  • Fluent in English
  • Able to provide written informed consent.

EXCLUSION CRITERIA (all sub-studies):

  • 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.

EXCLUSION CRITERIA (fMRI sub-studies):

  • 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.
  • Pregnant women (based on urine test completed within 24 hours prior to scan).
  • Individuals who are left-handed (based on self-report or score on handedness questionnaire) will be excluded from fMRI substudies.

EXCLUSION CRITERIA (placebo analgesia sub-studies):

-Participation in an NIH study of analgesia, as gleaned from CRIS.

Study Design

Enrollment

550 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

other: Substudy 1: Instructed subjects

Participants are instructed about outcomes

other: Substudy 1: Uninstructed subjects

Participants learn through experience

other: Substudy 2: heat group

Participants learn about heat outcomes through conditioning

other: Substudy 2: salt group

Participants learn about salt outcomes through conditioning

other: Substudy 2: sugar group

Participants learn about sugar outcomes through conditioning

no intervention: Substudy 3: healthy volunteers

All participants experience all outcomes, within subjects designs

other: Substudy 4: healthy volunteers

Participants are instructed to attend toward or away from the stimulus

other: Substudy 5: healthy volunteers

Participants experience both placebo and cue-based expectations within subjects

Interventions

Instructions

In sub-study 1, half the participants are instructed about outcomes, half learn through experience.

Attention

In sub-study 4, participants learn about outcomes and we manipulate attention toward or away from the pain.

Thermal 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.

Placebo instructions

In sub-study 5, we test whether placebo effects and expectancy cues modulate pain through similar mechanisms.

Primary outcome measure

  • Physiological responses (heart rate, skin conductance, respiration, pupil dilation, eye gaze position) [ Time Frame: During the study visit in response to painful and non-painful stimuli. ]
  • Pain perception (pain ratings) [ Time Frame: During the study visit in response to painful stimuli. ]
  • BOLD response in brain regions of interest measured using fMRI [ Time Frame: During the study visit in response to painful and non-painful stimuli. ]

Central Contacts and Locations

Central contacts

Adebisi O Ayodele, C.R.N.P.

(240) 593-4226bisi.ayodele@nih.gov

Lauren Y Atlas, Ph.D.

(301) 827-0214lauren.atlas@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

800-411-1222ccopr@nih.gov

More Information

Sponsor

National Center for Complementary and Integrative Health (NCCIH)

Last update posted

Sep 2, 2026

Last verified

Aug 31, 2026

Keywords

  • Pain
  • Visual Analogue Pain Scale
  • Placebo
  • Affective Neuroscience
  • Functional Magnetic Resonance Imaging (fMRI)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Center for Complementary and Integrative Health (NCCIH) on 2026-09-02.