The Role of Opioidergic Systems in Breathing Based Analgesia
- Conditions
- Pain
- Interventions
- Behavioral: Mindfulness MeditationBehavioral: Placebo MeditationBehavioral: Slow-BreathingOther: Saline
- Registration Number
- NCT03419858
- Lead Sponsor
- University of California, San Diego
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Mindfulness Meditation Group Mindfulness Meditation Subjects participated in four sessions (20 min/session) of mindfulness training. Participants were taught that perceived sensory events are "momentary" and "fleeting" and require no further evaluation. They were asked to close their eyes, relax and to focus on the flow of their breathing and "simply let go" of discursive thoughts. Mindfulness Meditation Group Saline Subjects participated in four sessions (20 min/session) of mindfulness training. Participants were taught that perceived sensory events are "momentary" and "fleeting" and require no further evaluation. They were asked to close their eyes, relax and to focus on the flow of their breathing and "simply let go" of discursive thoughts. Placebo Meditation Group Placebo Meditation The purpose of this intervention was to lead subjects to attend to one's breathing in a non-evaluative manner. Subjects were instructed to sit with a straight posture, closed eyes, and to take a deep, slow breaths every 2-3 minutes. Placebo Meditation Group Saline The purpose of this intervention was to lead subjects to attend to one's breathing in a non-evaluative manner. Subjects were instructed to sit with a straight posture, closed eyes, and to take a deep, slow breaths every 2-3 minutes. Slow-Breathing Group Slow-Breathing A validated (Chalaye et al., 2009) slow breathing training regimen was employed, using fluctuating light, to teach individuals to independently lower their respective respiration rate. Subjects practiced lowering their respiration rates across four, 20 minute sessions. Slow-Breathing Group Saline A validated (Chalaye et al., 2009) slow breathing training regimen was employed, using fluctuating light, to teach individuals to independently lower their respective respiration rate. Subjects practiced lowering their respiration rates across four, 20 minute sessions. Mindfulness Meditation Group Naloxone Subjects participated in four sessions (20 min/session) of mindfulness training. Participants were taught that perceived sensory events are "momentary" and "fleeting" and require no further evaluation. They were asked to close their eyes, relax and to focus on the flow of their breathing and "simply let go" of discursive thoughts. Placebo Meditation Group Naloxone The purpose of this intervention was to lead subjects to attend to one's breathing in a non-evaluative manner. Subjects were instructed to sit with a straight posture, closed eyes, and to take a deep, slow breaths every 2-3 minutes. Slow-Breathing Group Naloxone A validated (Chalaye et al., 2009) slow breathing training regimen was employed, using fluctuating light, to teach individuals to independently lower their respective respiration rate. Subjects practiced lowering their respiration rates across four, 20 minute sessions.
- Primary Outcome Measures
Name Time Method 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. 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 Outcome Measures
Name Time Method Pain Catastrophizing Scale (PCS) 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.
Respiration Rate Measures Up to 3 weeks A respiratory transducer (TSD 201; Biopac Systems) was placed around the chest to measure the participant's rate of respiration.
Treatment Effectiveness Scale 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.
Center for Epidemiological Studies Depression Scale (CES-D) 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.
Stress-Level Visual Analogue Scale 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.
Naloxone Symptom Assessments 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."
State Anxiety Inventory 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.
Cohen Perceived Stress Scale (CPS) 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.
Attitude Toward Treatment Scale (ATTS) 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.
Trial Locations
- Locations (1)
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States