The Role of Opioidergic Systems in Breathing Based Analgesia
Condition: Pain
MeSH terms: Respiratory Aspiration
Study type: Interventional
Phase: Early Phase 1

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.
    

Intervention name(s): Mindfulness Meditation; Placebo Meditation; Slow-Breathing; Naloxone; Saline
Intervention type(s): Behavioral; Behavioral; Behavioral; Drug; Other
Intervention description(s): A well-validated brief mindfulness-based mental training regimen [four sessions; 20 min/session] was used to teach patients to independently practice mindfulness meditation.; 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.; 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.; 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.; 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.
Other intervention name(s): mental training; mental training; mental training
Intervention MeSH terms: Naloxone
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: The study employed a double blind 3x2x2 crossover factorial design. Baseline pain intensity and pain unpleasantness ratings were assessed using visual analog scales (11 point) obtained before and after four, 5-minute noxious heat stimulation series (49°C). Study volunteers (20/group; 60 total) were randomized and subsequently participated in a four session (20min/session) mindfulness meditation, placebo-meditation, or slow-breathing training regimen. After training completion, subjects reported to the Wake Forest Clinical Research Unit to test the study hypotheses across two separate experimental sessions. Half of the study volunteers (n=10) from each group were administered naloxone (opioid antagonist; 0.15 mg/kg bolus+ 0.1mg/kg/hour infusion) and in the subsequent session were administered IV placebo-saline and vice versa.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Pain; Slow-Breathing; Mindfulness; Opioids; Placebo