Sleep Deprivation, Pain
Conditions
Brief summary
Twenty percent of Americans suffer from chronic pain. Sleep disturbance is similarly prevalent and among the most common and disabling neurobehavioral problems associated with chronic pain. This research is designed to evaluate the effects of disrupted sleep patterns on mood, inflammation, the perception of pain, and pain relief. This study will help researchers understand the relationship between sleep and pain, and how sleep disturbance might influence chronic pain conditions.
Detailed description
This research is being conducted in order to evaluate the effects of disrupted sleep patterns on mood, inflammation, the perception of pain, and pain relief. This study will help researchers understand the relationship between sleep and pain, and how sleep disturbance might influence chronic pain conditions. Healthy participants will undergo baseline sleep and sleep disruption conditions. Following undisturbed sleep and sleep disruption conditions, sensitivity to pain and analgesic response (via morphine or placebo administration) will be assessed using a heat-capsaicin pain model. This study will be conducted in 2 major parts-3 screening visits (2 outpatient and 1 inpatient) and 2 experimental inpatient visits. Part 1 of the study will involve a 1-week screening period. This will involve two separate screening visits lasting about 2 hours each. At Screening Visit 1, participants will complete questionnaires, an interview, and undergo toxicology screening. At Screening Visit 2, participants will complete questionnaires, undergo a physical exam, and be familiarized with pain testing procedures. At Screening Visit 3, participants will undergo an inpatient sleep study. Part 2 will involve two different inpatient admissions. The two admissions will be separated by at least two weeks. During each of the admissions, participants' sleep will be studied at night. The first admission will begin immediately following the overnight sleep study in Screening Visit 3. One of the admissions will be for one night and the other admission will be for three nights. For the one night admission, participants will sleep undisturbed for an 8-hour period. For the three night admission, participants will undergo sleep disruption for two nights in a row. On the third night, participants will be allowed to sleep undisturbed for 8 hours for recovery. During both inpatient admissions, pain testing procedures will be completed that will last approximately 5 hours during the day. During testing, small amounts of blood will be drawn for analysis. Participants will be randomly assigned to two groups. Group A will be given a standard dose of morphine during pain testing. Group B will be given a placebo during pain testing.
Interventions
DRUGMorphine
0.08mg/kg will be administered to participants randomly assigned to receive the drug via IV bolus during each quantitative sensory testing session (after one night of uninterrupted sleep and after 2 nights of forced awakenings).
DRUGSaline Placebo
Saline Placebo will administered to participants randomly assigned to receive the placebo via IV bolus during each quantitative sensory testing session (after one night of uninterrupted sleep and after 2 nights of forced awakenings).
BEHAVIORALForced Awakenings
Participants will be awakened each hour during an 8 hour sleep opportunity period. One of the awakenings is for 60 minutes and randomly determined. The other 7 awakenings are for 20 minutes each, and are randomly scheduled to occur in either the first second or third tertile of each hour. The maximum total sleep time a participant will receive is 280 minutes.
BEHAVIORALUninterrupted Sleep
Participants will receive an 8 hour period of undisturbed sleep
Sponsors
National Institute on Drug Abuse (NIDA)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 48 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy * Age 18-48 * Meets Research Diagnostic Criteria for Normal Sleepers * Stable sleep phase within 21:00 and 08:00 * Total sleep time between 6.5 and 8.5 hours per night * Sleep efficiency ≥85% * Epworth Sleepiness Scale Score \<10 * Non-smoker/non-nicotine users * Low Caffeine Users (≤2 cups per day)
Exclusion criteria
* Body Mass Index ≥35 * Lifetime history of chronic pain (\>6 months) * Acute pain * Significant medical or psychiatric morbidity within 6 months * Lifetime history of bipolar disorder, psychotic disorder, serious recurrent major depression, serious post-traumatic stress disorder, or seizure disorder * Respiratory, hepatic, renal, or cardiac conditions that would contraindicate opioid use * Lifetime history of alcohol or substance abuse or dependence * Lifetime history of opioid use \>36 doses or \>7 days of consecutive use * Prior adverse reaction to general anesthetics, opioids, or capsaicin * Clinically significant abnormal complete blood count or comprehensive metabolic profile * Positive toxicology screen for opioids or recreational drugs * Pregnant or lactating women * Significant pre-admission psychological distress (T-scores \>64 on the Brief Symptom Inventory Global Scales) * Significant lifetime history of serious head injury that is determined to influence pain processing or sleep systems
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Spinal Sensitization as Assessed by Area of Secondary Hyperalgesia (2HA) After Two Nights of Uninterrupted Sleep and Two Nights of 8 Forced Awakenings | Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep | The area of secondary hyperalgesia (2HA) to mechanical stimulation was quantified by stimulating along eight linear paths near the capsaicin treated site using a 15 gram nonpainful von Frey filament. Stimulation occurred until the participant reported a change in sensation from which a border was marked on the skin. The degree of 2HA was assessed by measuring the total surface area (mm\^2) of the marked borders. Data were collapsed by group to analyze the effects of FA vs US, irrespective of randomization group. Our Primary Secondary Hyperalgesia outcome was measured prior to injection of either morphine or placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Analgesia as Assessed by Analgesia Index (Seconds) | Next day after 2 nights of forced awakenings or uninterrupted sleep | After 2 nights of forced awakenings and after two nights of uninterrupted sleep, opioid analgesia will be assessed by an analgesia index. The analgesia index is calculated using withdrawal latency during cold pressor testing (lasting maximum of 300 seconds). Cold Pressor Testing is done before and after morphine or placebo injection. The difference in withdrawal time before and after morphine or placebo injection is the analgesia index with a minimum score of -300 seconds and maximum score of 300 seconds. These data were log transformed. Mean analgesia index was then calculated for each group. Higher means represent greater analgesia. |
| Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Next day after 2 nights of forced awakenings or uninterrupted sleep, every 60 minutes up to 7 hours | After 2 nights of forced awakenings, and two nights of uninterrupted sleep, blood is drawn (approximately every 60 minutes) during quantitative sensory testing; 4 hours pre-morphine/placebo administration and 2 hours post-morphine/placebo administration to examine markers of inflammation. Two blood samples for each participant are analyzed at 7 separate time points. The marker of inflammation assessed is the number of peripheral blood mononuclear cells expressing Interleukin-6 (IL-6), and the outcome measure represents the mean change in IL-6 levels pre and post stimulation with lipopolysaccharide (LPS). Cellular IL-6 expression was was quantified via flow cytometry. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Total Sleep Time | Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep. | The degree of sleep deprivation will be assessed by total sleep time (TST) in minutes during the uninterrupted sleep condition compared to the forced awakenings conditions. |
Countries
United States
Participant flow
Recruitment details
During screening for the study we evaluated whether participants were generally healthy, pain free, and good sleepers. We screened 255 to obtain 100 participants who met criteria and were randomized to the experimental portion of the study. The experimental phase occurred at an inpatient clinical research unit.
Participants by arm
| Arm | Count |
|---|---|
| Morphine US Then Morphine FA Participants randomized to receive Morphine and the Uninterrupted Sleep (US) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of uninterrupted sleep (US). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of forced awakenings (FA). They will receive the Morphine injection (0.08mg/kg) via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the US and FA sleep conditions are completed. | 25 |
| Morphine FA Then Morphine US Participants randomized to receive Morphine and the Forced Awakenings (FA) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of forced awakenings (FA). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of uninterrupted sleep (US). They will receive the Morphine injection (0.08mg/kg) via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the FA and US sleep conditions are completed. | 29 |
| Placebo US Then Placebo FA Participants randomized to receive the saline placebo and the Uninterrupted Sleep (US) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of uninterrupted sleep (US). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of forced awakenings (FA). They will receive the injection via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the US and FA sleep conditions are completed. | 24 |
| Placebo FA Then Placebo US Participants randomized to receive the saline placebo and the Forced Awakenings (FA) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of forced awakenings (FA). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of uninterrupted sleep (US). They will receive the injection via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the FA and US sleep conditions are completed. | 22 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Intervention 1 (2 Nights) | Adverse Event | 0 | 1 | 0 | 0 |
| Intervention 1 (2 Nights) | Physician Decision | 1 | 1 | 0 | 0 |
| Intervention 1 (2 Nights) | Protocol Violation | 1 | 0 | 1 | 0 |
| Intervention 1 (2 Nights) | Withdrawal by Subject | 3 | 0 | 2 | 4 |
Baseline characteristics
| Characteristic | Morphine US Then Morphine FA | Total | Placebo FA Then Placebo US | Placebo US Then Placebo FA | Morphine FA Then Morphine US |
|---|---|---|---|---|---|
| Age, Continuous | 27.1348 years STANDARD_DEVIATION 5.97835 | 28.0581 years STANDARD_DEVIATION 6.81392 | 27.7272 years STANDARD_DEVIATION 8.18124 | 27.3609 years STANDARD_DEVIATION 5.22747 | 29.6819 years STANDARD_DEVIATION 7.54226 |
| Body Mass Index | 26.1490 kg/m^2 STANDARD_DEVIATION 4.16713 | 25.7235 kg/m^2 STANDARD_DEVIATION 3.93648 | 25.7134 kg/m^2 STANDARD_DEVIATION 4.17552 | 25.8440 kg/m^2 STANDARD_DEVIATION 3.63156 | 25.2645 kg/m^2 STANDARD_DEVIATION 3.95007 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 11 Participants | 1 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 37 Participants | 11 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 10 Participants | 45 Participants | 10 Participants | 11 Participants | 14 Participants |
| Sex: Female, Male Female | 14 Participants | 58 Participants | 17 Participants | 12 Participants | 15 Participants |
| Sex: Female, Male Male | 11 Participants | 42 Participants | 5 Participants | 12 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 49 | 0 / 42 | 0 / 43 |
| other Total, other adverse events | 8 / 52 | 7 / 49 | 1 / 42 | 2 / 43 |
| serious Total, serious adverse events | 0 / 52 | 0 / 49 | 0 / 42 | 0 / 43 |
Outcome results
Primary
Spinal Sensitization as Assessed by Area of Secondary Hyperalgesia (2HA) After Two Nights of Uninterrupted Sleep and Two Nights of 8 Forced Awakenings
The area of secondary hyperalgesia (2HA) to mechanical stimulation was quantified by stimulating along eight linear paths near the capsaicin treated site using a 15 gram nonpainful von Frey filament. Stimulation occurred until the participant reported a change in sensation from which a border was marked on the skin. The degree of 2HA was assessed by measuring the total surface area (mm\^2) of the marked borders. Data were collapsed by group to analyze the effects of FA vs US, irrespective of randomization group. Our Primary Secondary Hyperalgesia outcome was measured prior to injection of either morphine or placebo.
Time frame: Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Morphine US | Spinal Sensitization as Assessed by Area of Secondary Hyperalgesia (2HA) After Two Nights of Uninterrupted Sleep and Two Nights of 8 Forced Awakenings | 1276.25 mm^2 | Standard Deviation 1096.761 |
| Morphine FA | Spinal Sensitization as Assessed by Area of Secondary Hyperalgesia (2HA) After Two Nights of Uninterrupted Sleep and Two Nights of 8 Forced Awakenings | 1582.67 mm^2 | Standard Deviation 1590.784 |
| Placebo US | Spinal Sensitization as Assessed by Area of Secondary Hyperalgesia (2HA) After Two Nights of Uninterrupted Sleep and Two Nights of 8 Forced Awakenings | 1302.93 mm^2 | Standard Deviation 1301.457 |
| Placebo FA | Spinal Sensitization as Assessed by Area of Secondary Hyperalgesia (2HA) After Two Nights of Uninterrupted Sleep and Two Nights of 8 Forced Awakenings | 1447.9 mm^2 | Standard Deviation 1322.52 |
Secondary
Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation
After 2 nights of forced awakenings, and two nights of uninterrupted sleep, blood is drawn (approximately every 60 minutes) during quantitative sensory testing; 4 hours pre-morphine/placebo administration and 2 hours post-morphine/placebo administration to examine markers of inflammation. Two blood samples for each participant are analyzed at 7 separate time points. The marker of inflammation assessed is the number of peripheral blood mononuclear cells expressing Interleukin-6 (IL-6), and the outcome measure represents the mean change in IL-6 levels pre and post stimulation with lipopolysaccharide (LPS). Cellular IL-6 expression was was quantified via flow cytometry.
Time frame: Next day after 2 nights of forced awakenings or uninterrupted sleep, every 60 minutes up to 7 hours
Population: For some participants we could not collect blood samples for all time points and testing sessions. This explains the differences in the numbers of samples analyzed at various timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Morphine US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 7 | 36.47 percentage of IL-6 expression | Standard Deviation 18.9 |
| Morphine US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 5 | 38.67 percentage of IL-6 expression | Standard Deviation 17.93 |
| Morphine US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 2 | 45.44 percentage of IL-6 expression | Standard Deviation 22.95 |
| Morphine US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 4 | 43.96 percentage of IL-6 expression | Standard Deviation 18.2 |
| Morphine US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 6 | 36.83 percentage of IL-6 expression | Standard Deviation 19.39 |
| Morphine US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 3 | 45.99 percentage of IL-6 expression | Standard Deviation 19.12 |
| Morphine US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 1 | 41.98 percentage of IL-6 expression | Standard Deviation 21.18 |
| Morphine FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 7 | 39.92 percentage of IL-6 expression | Standard Deviation 19.6 |
| Morphine FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 3 | 48.99 percentage of IL-6 expression | Standard Deviation 18.96 |
| Morphine FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 6 | 39.15 percentage of IL-6 expression | Standard Deviation 21.23 |
| Morphine FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 1 | 51.82 percentage of IL-6 expression | Standard Deviation 21.13 |
| Morphine FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 2 | 51.84 percentage of IL-6 expression | Standard Deviation 20.34 |
| Morphine FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 4 | 46.94 percentage of IL-6 expression | Standard Deviation 17.81 |
| Morphine FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 5 | 43.45 percentage of IL-6 expression | Standard Deviation 18.3 |
| Placebo US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 3 | 40.76 percentage of IL-6 expression | Standard Deviation 20.1 |
| Placebo US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 1 | 42.91 percentage of IL-6 expression | Standard Deviation 19.53 |
| Placebo US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 5 | 38.71 percentage of IL-6 expression | Standard Deviation 19.11 |
| Placebo US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 6 | 35.64 percentage of IL-6 expression | Standard Deviation 18.58 |
| Placebo US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 2 | 42.93 percentage of IL-6 expression | Standard Deviation 21.81 |
| Placebo US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 7 | 35.49 percentage of IL-6 expression | Standard Deviation 17.03 |
| Placebo US | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 4 | 39.06 percentage of IL-6 expression | Standard Deviation 20.48 |
| Placebo FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 7 | 35.25 percentage of IL-6 expression | Standard Deviation 19.35 |
| Placebo FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 5 | 34.63 percentage of IL-6 expression | Standard Deviation 20.74 |
| Placebo FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 1 | 43.32 percentage of IL-6 expression | Standard Deviation 19.04 |
| Placebo FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 2 | 43.79 percentage of IL-6 expression | Standard Deviation 18.01 |
| Placebo FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 3 | 41.65 percentage of IL-6 expression | Standard Deviation 21.87 |
| Placebo FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 6 | 36.28 percentage of IL-6 expression | Standard Deviation 19.38 |
| Placebo FA | Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation | Timepoint 4 | 41.34 percentage of IL-6 expression | Standard Deviation 21.36 |
Secondary
Opioid Analgesia as Assessed by Analgesia Index (Seconds)
After 2 nights of forced awakenings and after two nights of uninterrupted sleep, opioid analgesia will be assessed by an analgesia index. The analgesia index is calculated using withdrawal latency during cold pressor testing (lasting maximum of 300 seconds). Cold Pressor Testing is done before and after morphine or placebo injection. The difference in withdrawal time before and after morphine or placebo injection is the analgesia index with a minimum score of -300 seconds and maximum score of 300 seconds. These data were log transformed. Mean analgesia index was then calculated for each group. Higher means represent greater analgesia.
Time frame: Next day after 2 nights of forced awakenings or uninterrupted sleep
Population: Each participant had to do four visits and two testing sessions to be termed complete. The data needed for analysis for this outcome measure was obtained from some participants but not all who completed or couldn't complete the entire study. This explains the differences in the number of units analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Morphine US | Opioid Analgesia as Assessed by Analgesia Index (Seconds) | 0.315 seconds (log transformed) | Standard Deviation 0.54 |
| Morphine FA | Opioid Analgesia as Assessed by Analgesia Index (Seconds) | 0.156 seconds (log transformed) | Standard Deviation 0.712 |
| Placebo US | Opioid Analgesia as Assessed by Analgesia Index (Seconds) | -0.124 seconds (log transformed) | Standard Deviation 0.346 |
| Placebo FA | Opioid Analgesia as Assessed by Analgesia Index (Seconds) | -0.006 seconds (log transformed) | Standard Deviation 0.263 |
Other Pre-specified
Total Sleep Time
The degree of sleep deprivation will be assessed by total sleep time (TST) in minutes during the uninterrupted sleep condition compared to the forced awakenings conditions.
Time frame: Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep.
Population: Each participant had to do four visits to be termed complete. The data needed for analysis for this outcome measure was obtained from some participants but not all who completed or couldn't complete the entire study. This explains the differences in the numbers analyzed for each total sleep time.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Morphine US | Total Sleep Time | TST: Forced Awakenings-Night 1 | 217.4556 minutes | Standard Deviation 46.00094 |
| Morphine US | Total Sleep Time | TST: Forced Awakenings-Night 2 | 270.3333 minutes | Standard Deviation 35.23125 |
| Morphine US | Total Sleep Time | TST: Uninterrupted Sleep-Night 2 | 435.2045 minutes | Standard Deviation 41.1612 |
| Morphine US | Total Sleep Time | TST: Uninterrupted Sleep-Night 1 | 442.8909 minutes | Standard Deviation 23.06461 |
| Morphine FA | Total Sleep Time | TST: Uninterrupted Sleep-Night 2 | 420.1375 minutes | Standard Deviation 71.39364 |
| Morphine FA | Total Sleep Time | TST: Uninterrupted Sleep-Night 1 | 425.0280 minutes | Standard Deviation 52.40921 |
| Morphine FA | Total Sleep Time | TST: Forced Awakenings-Night 1 | 225.4192 minutes | Standard Deviation 38.47452 |
| Morphine FA | Total Sleep Time | TST: Forced Awakenings-Night 2 | 258.1083 minutes | Standard Deviation 29.47026 |
| Placebo US | Total Sleep Time | TST: Uninterrupted Sleep-Night 2 | 439.0417 minutes | Standard Deviation 47.06713 |
| Placebo US | Total Sleep Time | TST: Forced Awakenings-Night 1 | 235.1727 minutes | Standard Deviation 50.91526 |
| Placebo US | Total Sleep Time | TST: Uninterrupted Sleep-Night 1 | 443.2375 minutes | Standard Deviation 38.99631 |
| Placebo US | Total Sleep Time | TST: Forced Awakenings-Night 2 | 267.7714 minutes | Standard Deviation 16.9008 |
| Placebo FA | Total Sleep Time | TST: Uninterrupted Sleep-Night 2 | 441.1400 minutes | Standard Deviation 35.93814 |
| Placebo FA | Total Sleep Time | TST: Uninterrupted Sleep-Night 1 | 435.1467 minutes | Standard Deviation 29.12669 |
| Placebo FA | Total Sleep Time | TST: Forced Awakenings-Night 2 | 261.9941 minutes | Standard Deviation 32.01372 |
| Placebo FA | Total Sleep Time | TST: Forced Awakenings-Night 1 | 252.0950 minutes | Standard Deviation 32.7055 |