Mechanisms of Sleep Disruption Hyperalgesia

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.

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