Skip to main content
OpenTrials
Completed

NCT Number: NCT03419858

The Role of Opioidergic Systems in Breathing Based Analgesia

The purpose of this psychophysical and pharmacologic study is to determine if slow-breathing induced pain relief is mediated by endogenous opioids in response to intravenous (IV) administration of the opioid antagonist naloxone during noxious heat stimulation. We were also interested in disentangling the endogenous analgesic mechanisms supporting mindfulness-based analgesia.

Completed

Looking for future studies?

Notify Me

Key information

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

About this study

The proposed study will employ a graded analytical approach to compare mindfulness to placebo-meditation and a slow-breathing exercise in response to double-blind intravenous administration (IV) of naloxone/placebo-saline and noxious heat stimulation. The aim of this study is to determine if slow-breathing induced analgesia is associated with the release of endogenous opioids. The proposed study will disentangle the specific stage of cognitive and/or respiration-based involvement (if any) of opioidergically mediated pain relief, a critical step in identifying the specific analgesic mechanisms corresponding to mindfulness based cognitive techniques.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Normal volunteers with no history of chronic pain problems
  • Volunteers had no prior meditation experience
  • Volunteers could be male and non-pregnant females.
  • Volunteers of all ethnic backgrounds were included.

Exclusion criteria

  • Female volunteers could not be pregnant.
  • They could not be taking opioids or antidepressants.
  • Subjects with a repeated history of syncope, loss of consciousness, light headedness, nausea, dizziness, or vomiting in response to needles or blood could not participate in the study.
  • Subject could not be using exogenous opiates for the complete duration of the study.

Treatment and study plan

Mindfulness Meditation

Behavioral

A well-validated brief mindfulness-based mental training regimen [four sessions; 20 min/session] was used to teach patients to independently practice mindfulness meditation.

Other names: mental training

Placebo Meditation

Behavioral

A well-validated brief meditation-based mental training regimen [four sessions; 20 min/session] was used to teach patients to independently practice closing their eyes and take a deep breath every few minutes.

Other names: mental training

Slow-Breathing

Behavioral

Study volunteers practiced lowering their breathing rate, across four, 20 minute training sessions, in response to a fluctuating light with the guidance of a trained facilitator.

Other names: mental training

naloxone

Drug

A 0.15 mg/kg bolus dose of naloxone (Naloxone Hydrichloride, Amphastar Pharmaceuticals, Inc., Rancho Cucamonga, California) in 25ml normal saline was administered over 10 minutes. We also administered a supplementary IV infusion dose of 0.1mg/kg/hour naloxone immediately after bolus infusion ceased till the end of the experiment.

Saline

Other

A 0.15 mg/kg bolus dose of saline in 25ml normal saline was administered over 10 minutes. We also administered a supplementary IV infusion dose of 0.1mg/kg/hour saline immediately after bolus infusion ceased till the end of the experiment.

Primary outcomes

  1. Change in Visual Analog Scale Pain intensity and Unpleasantness ratings as a function of each respective cognitive manipulations and activation in response to naloxone and/or saline.

    Time frame: Up to 3 weeks

    The visual analog scale (VAS) measures pain ratings that are assessed in response to noxious (49°C) thermal stimuli applied to the back of the right calf muscle.

    Pain intensity and unpleasantness ratings will be assessed with a Visual Analog Scale. The minimum rating ("0") is designated as "no pain" whereas the maximum ("10") is labeled as "most intense imaginable" or "most unpleasant imaginable". Higher values corresponded to higher perceived pain ratings.

    Pain ratings were assessed at baseline (session 1) and again at sessions six and seven to determine the impact of the mental training regimens. At session six and seven, subjects were given an infusion of either naloxone or saline to address the potential contribution of the opioidergic system in the cognitive modulation of pain.

Secondary outcomes

  1. Respiration Rate Measures

    Time frame: Up to 3 weeks

    A respiratory transducer (TSD 201; Biopac Systems) was placed around the chest to measure the participant's rate of respiration.

  2. State Anxiety Inventory

    Time frame: up to 3 weeks

    This inventory is a 20 question test used to measure a subject's state of anxiety. A numeric value between 1 (Not at all) and 4 (Very Much So) is provided in response to each statement. The range of scores for this test is between 20 and 80, with higher scores reflecting higher estimates of anxiety.

  3. Pain Catastrophizing Scale (PCS)

    Time frame: up to 3 weeks

    The PCS is a 13 item scale, with each item rated on a 5-point scale between: 0 (Not at all) and 4 (all the time). The PCS is broken into three subscales including: magnification, rumination, and helplessness. The total range of scores is between 0-52 with higher values reflecting more salient impacts of pain on one's day to day experience.

  4. Cohen Perceived Stress Scale (CPS)

    Time frame: up to 3 weeks

    The CPS is a series of 10 temporally constrained (i.e. in the last month) questions meant to ascertain the relative frequency of stressors in one's life, ranging from never (scored as 0) to very often (scored as 4). All positively stated questions are reversed scored and then all items are summed to yield a final estimate of stress. The higher the score the higher the level of stress.

  5. Treatment Effectiveness Scale

    Time frame: up to 3 weeks

    A VAS assessed the effectiveness of the study's intervention. Values on this scale vary continuously between 0 (not effective) and 10 (most effective imaginable). Higher values indicate a subject's greater confidence in the perceived treatment effectiveness.

  6. Attitude Toward Treatment Scale (ATTS)

    Time frame: up to 3 weeks

    The ATTS was used to monitor a participant's impressions and attitudes about the interventions used in this study. It supplies 5 multiple-choice questions answered on a 10 point scale, ranging from 0 (not logical) to 9 (very logical). Higher scores reflect more positive subject impressions about the therapeutic interventions.

  7. Center for Epidemiological Studies Depression Scale (CES-D)

    Time frame: up to 3 weeks

    This is a brief self-report questionnaire used to measure the severity of depressive symptoms. The CES-D is an inventory of 20 self-report items regarding depressive symptoms. Each question is graded on a 0 to 3 point scale with 0 representing "not at all" and 3 representing "a lot". Four questions (4,8,12, and 16) are reverse scored. A score of 15 or higher indicates a risk for depression.

  8. Stress-Level Visual Analogue Scale

    Time frame: up to 3 weeks

    A VAS was employed to measure subjective stress ratings. Values on this scale vary continuously between 0 (no stress) to 10 (most stress imaginable). Higher values indicate higher assessments of the subject's stress level.

  9. Naloxone Symptom Assessments

    Time frame: Up to 3 weeks

    A numerical ratings scale was used to assess potential naloxone related symptomology after each clinical research unit session. "0" was designated as "non-existent" and "6" was characterized as "extremely strong". We measured symptoms corresponding to "dry mouth, dry skin, blurred vision, sedation, nausea, dizziness, and headache."

Sponsors and collaborators

Lead sponsor

University of California, San Diego

Other

Registry information

Official study title

The Role of Endogenous Opioidergic Systems in Breathing Based Analgesia

Important dates

Study start
2017
Primary completion
2017
Study completion
2017
First posted
Feb 5, 2018
Registry last updated
Jun 11, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.