Study of Pain Processing in Subjects Suffering From Obstructive Sleep Apnea

Completed

Conditions: Sleep Apnea, Obstructive

Interventions: Drug: Remifentanil
Procedure: Cold pain threshold and tolerance
Device: Heat pain threshold and tolerance
Procedure: Polysomnography

Registration Number: NCT00672737

Lead Sponsor: Stanford University

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 56

Inclusion Criteria

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

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 & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Males at risk for OSA	Cold pain threshold and tolerance	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.
Males at risk for OSA	Heat pain threshold and tolerance	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.
Males at risk for OSA	Polysomnography	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.
Males at risk for OSA	Remifentanil	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.

Primary Outcome Measures

Name	Time	Method
Experimental Cold-induced Pain - IGFBP-1	2 to 3 weeks	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.
Experimental Heat-induced Pain - IGFBP-1	2 to 3 weeks	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.
Experimental Cold-induced Pain - SaO2	2 to 3 weeks	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.
Experimental Heat-induced Pain - SaO2	2 to 3 weeks	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.