Study of Pain Processing in Subjects Suffering From Obstructive Sleep Apnea

Experimental Pain Processing and Autonomic Function in Subjects Suffering From Obstructive Sleep Apnea

We would like to test the effect of opioid medication on pain sensitivity in subjects who have been diagnosed with a sleep disorder called Obstructive Sleep Apnea (OSA) compared to other subjects without OSA. Patients with OSA may have an altered sensitivity to the sedative, analgesic, and respiratory depressant effects of opioids.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea, Obstructive
• Intervention / Treatment: Drug: Remifentanil; Procedure: Cold pain threshold and tolerance; Device: Heat pain threshold and tolerance; Procedure: Polysomnography

Detailed Description

The purpose of the study is to test the hypothesis that patients who suffer from moderate-to-severe OSA have increased pain thresholds and are more sensitive to the analgesic effects of opioids compared to patients with normal sleep-related breathing physiology. We will evaluate the effect of remifentanil, a short acting mu-opioid receptor agonist, on pain using an experimental heat and cold-induced pain tests, and compare it between volunteers with and without a polysomnography (PSG)-based diagnosis of obstructive sleep apnea.

• Study Type: Observational
• Enrollment (Actual): 56

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Males at risk for obstructive sleep apnea (OSA). We invited male volunteers (18 55 years old) with a history of habitual snoring and/or a formal diagnosis of OSA to participate in a study evaluating sleep and experimental pain processing.

Description

Inclusion Criteria:1. Male 2 .18 - 55 years of age 3. Body mass index (BMI) lower or equal to 30 kg/m2 4. Absence of severe systemic disease that results in functional limitations (i.e. poorly controlled hypertension, angina pectoris, prior myocardial infarction, pulmonary disease that limits activity) 5.Subjects must be able to comprehend spoken and written English

Exclusion Criteria:1. Major psychiatric, neurological, or neuromuscular disorder 2. Known diabetes mellitus or thyroid disease 3. Allergy to study medication (remifentanil) 4. History of addiction 5. Alcohol consumption which exceeds 2 drinks per day and /or drug abuse. 6. Chronic or acute use of opioids, or other medications affecting the CNS.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Males at risk for OSA; Males at risk for obstructive sleep apnea were invited to have a "sleep study" either at home or at Stanford Sleep Center. A week after their sleep study (Polysomnography), all volunteers underwent quantitative sensory testing in the laboratory, during which their pain thresholds and tolerances to heat (Heat pain threshold and tolerance) and cold (Cold pain threshold and tolerance) stimuli were assessed, under two different concentrations (1 and 2 mcg/mL, in randomized order) of remifentanil, a short-acting opioid, given as a computer-controlled infusion.

Drug: Remifentanil; Remifentanil was administered as a computer-controlled infusion, targeting two different effect site concentrations, 1 and 2 mcg/mL, in randomized order.; Procedure: Cold pain threshold and tolerance; Ice water was used to assess cold-related pain threshold and tolerance, defined as the time that the volunteers could keep their hands in the water before they started feeling pain or this feeling becomes unbearable, for threshold and tolerance, respectively.; Device: Heat pain threshold and tolerance; TSAII Neuroanalyzer (Medoc Advanced Medical Systems, Durham, NC), was used to assess the heat-related pain and tolerance of the volunteers defined as the respective temperatures where they started feeling as painful or unbearable.; Procedure: Polysomnography; All volunteers underwent a polysomnography study at home or at Stanford Sleep Center, approximately one week before their experimental pain assessment in the laboratory; Other Names: sleep study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Experimental Cold-induced Pain - IGFBP-1	The effect of insulin growth factor binding protein-1 (IGFBP-1), a serum hypoxia marker, on the change of cold-induced pain thresholds under remifentanil was estimated using a mixed linear regression model. The results were expressed by the estimated beta (95% CI), indicating how much the change in the cold pain threshold (expressed in seconds) under remifentanil, was altered per unit of change in the IGFBP-1. For example, for every 1-pg/mL increase in the serum level of IGFBP-1, cold pain threshold will additionally increase by 0.0025 seconds for every 1-mcg/mL increase in the plasma level of remifentanil.	2 to 3 weeks
Experimental Heat-induced Pain - IGFBP-1	The effect of arterial oxyhemoglobin desaturation during sleep (chronic intermittent hypoxia expressed by insulin growth factor binding protein-1 (IGFBP-1), a serum hypoxia marker, on the change of heat-induced pain thresholds under remifentanil was estimated using a mixed linear regression model. The results were expressed by the estimated betas (95% CI), indicating how much the change in the heat pain threshold (expressed in C') under remifentanil, was altered per unit of change in the IGFBP-1. For example, for every 1-pg/mL increase in serum level of IGFBP-1, the heat pain threshold will additionally decrease by 0.0001 'C for every 1-mcg/mL increase in the plasma level of remifentanil.	2 to 3 weeks
Experimental Cold-induced Pain - SaO2	The effect of arterial oxyhemoglobin desaturation during sleep (chronic intermittent hypoxia expressed by nadir SaO2 during polysomnography) on the change of cold-induced pain thresholds under remifentanil was estimated using a mixed linear regression model. The results were expressed by the estimated betas (95% CI), indicating how much the change in the cold pain threshold (expressed in seconds) under remifentanil, was altered per unit of change in the SaO2. For example, for every 1-%-absolute decrease in the nadir SaO2, the cold pain threshold will additionally increase by 0.9694 seconds for every 1-mcg/mL increase in the plasma level of remifentanil.	2 to 3 weeks
Experimental Heat-induced Pain - SaO2	The effect of arterial oxyhemoglobin desaturation during sleep (chronic intermittent hypoxia expressed by nadir SaO2 during polysomnography), on the change of heat-induced pain thresholds under remifentanil was estimated using a mixed linear regression model. The results were expressed by the estimated betas (95% CI), indicating how much the change in the heat pain threshold (expressed in C') under remifentanil, was altered per unit of change in the SaO2. For example, for every 1-%-absolute decrease in the nadir SaO2, the heat pain threshold will additionally increase by 0.0172 'C for every 1-mcg/mL increase in the plasma level of remifentanil.	2 to 3 weeks

Collaborators and Investigators

• Sponsor: Stanford University

Publications and helpful links

General Publications

• Doufas AG, Tian L, Padrez KA, Suwanprathes P, Cardell JA, Maecker HT, Panousis P. Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea. PLoS One. 2013;8(1):e54807. doi: 10.1371/journal.pone.0054807. Epub 2013 Jan 29.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (ACTUAL): August 1, 2010
• Study Completion (ACTUAL): August 1, 2010

Study Registration Dates

• First Submitted: May 2, 2008
• First Submitted That Met QC Criteria: May 5, 2008
• First Posted (ESTIMATE): May 6, 2008

Study Record Updates

• Last Update Posted (ACTUAL): August 7, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil
• Other Study ID Numbers: SU-01222008-985; 10374

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO