Sensory and Opioid Mechanisms of Affective Touch
Condition: Pain; Touch
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Background:

      Medicines called opioids are used to treat pain. The body also produces opioids. These are
      called endorphins. Researchers want to learn more about how these natural opioids work. This
      might lead to new therapies for conditions like depression, anxiety, and chronic pain.

      Objective:

      To determine how opioids affect how pleasant or unpleasant it feels when the skin is touched,
      compressed, or heated.

      Eligibility:

      Healthy right-handed adults ages 18-50.

      Design:

      Participants will be screened under another protocol.

      Participants will have 2 study visits with the same procedures, at least 1 day apart. Each
      visit will last 3-4 hours.

      Participants will wear shorts or change into scrubs so researchers can test on their legs.

      Participants will answer questions and have urine tests.

      Participants will have a brain magnetic resonance imaging (MRI) scan. The scanner is a metal
      cylinder in a strong magnetic field. Participants will lie on a table that slides in and out
      of the cylinder. A device called a coil will be placed over the head.

      During MRI, participants will have sensory testing. They will get several types of touch to
      the calf of the leg. These include gentle brushing of the skin, gentle compression of the
      calf with an inflation sleeve, and heat stimuli.

      Participants will have an intravenous line placed each day. They will get naloxone 1 day and
      saline the other day. Participants will not be told which they get. Naloxone is a drug that
      blocks opioid receptors.

      The MRI and sensory testing will then be repeated.

      After each stimuli block, participants will rate the sensations as well as their mood and
      calmness/anxiety.
    

Detailed description: 
      Objective: Our recent pilot study found evidence suggesting that blocking endogenous opioid
      release increases the pleasantness associated with having the skin stroked. Deep pressure
      touch (observed in hugs and massage) also typically conveys a sense of pleasantness. This
      increased pleasantness contrasts with evidence that blocking endogenous opioid release
      increases pain. The current study will examine the role of endogenous opioids in the
      pleasantness of light skin stroking and deep pressure touch, and contrast it with their role
      in the unpleasantness of a painful heat stimulus. Further, it will examine the neural basis
      of observed perceptual changes, using fMRI. This study constitutes the first study of the K99
      phase of a K99/R00 grant application recently submitted to National Center for Complementary
      and Integrative Health (NCCIH) by Dr. Laura Case.

      Study Population: 30 healthy participants will be enrolled in the study.

      Design: Participants will receive intravenous saline or intravenous naloxone on separate days
      to investigate the effect of mu-opioid antagonism on the intensity and pleasantness of
      superficial and deep affective touch and the intensity and unpleasantness of cutaneous heat
      pain. Using a double-blind cross-over design, functional Magnetic Resonance Imaging (fMRI)
      will be conducted during sensory testing before and after the infusion of each drug to
      examine the neural mediation of opioid effects on touch perception. Ratings of mood, anxiety,
      pain intensity, pleasantness/unpleasantness, wanting and liking will also be collected
      throughout the study session.

      Outcome measures: We will compare subjective ratings (mood, calmness, anxiety, pleasantness,
      wanting, liking, pain intensity and unpleasantness) during naloxone and saline to: 1)
      Determine whether naloxone increases the pleasantness and/or intensity of affective touch
      (light brush and deep compression); 2) Determine whether naloxone increases the
      unpleasantness and/or intensity of cutaneous heat pain; 3) Determine the role of mood or
      anxiety changes in mediating the effect of endogenous opioids on these perceptual measures;
      3) Determine changes in the brain activation related to these effects.
    

Intervention name(s): Placebo; Naloxone
Intervention type(s): Other; Drug
Intervention description(s): saline; We will be using naloxone at normal clinical doses as the study drug. Naloxone is an opiate antagonist and has been used since the 1960 s to reverse the effects of opiate overdoses.
Intervention MeSH terms: Naloxone
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: NALOXONE; fMRI; Functional Magnetic Resonance Imaging (fMRI)