A Brain Imaging Study of Opioid (Morphine) and Non-opioid (Ketorolac) Conditioning Effects

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 51

Inclusion Criteria

Healthy male and female adults, aged 21-50
No contraindications to fMRI scanning
Within 15% of normal BMI
Right handed (dominant hand is right hand)
Have taken an opioid drug at least once in the past (for example, after a surgery)

Exclusion Criteria

Current or past history of major medical, neurological, or psychiatric illness
Women who are pregnant or breast feeding, have gone through menopause, or have irregular menstrual cycles (length of cycle must be within 26 to 32 days)
Contraindications to morphine administration:
- i) Hypersensitivity to morphine or other phenanthrene-derivative opioid agonists (codeine, oxycodone, etc.), morphine salts, or any component of the product
- ii) Concomitant use of other CNS depressants including antihistamines or alcohol
- iii) History of drug or alcohol abuse
- iv) History of head trauma
- v) History of liver problems
- vi) Pre-existing respiratory conditions (ex. COPD, asthma)
- vii) Current use of any drugs that interact with morphine
Contraindications to ketorolac administration
- i) Allergic-type reaction, or urticaria in response to exposure to aspirin or other NSAIDS
- ii) Concomitant aspirin or NSAID use
- iii) Hypersensitivity previously demonstrated to ketorolac tromethamine or to any product component
- iv) Peptic ulcer disease (active or history), or other gastrointestinal problems
- vi) Current use of any drugs that interact with ketorolac (ex. heparin/warfarin)
- vii) History of bleeding disorder
- viii) Low body weight, under 50 kg
Contraindications to fMRI scanning (including cardiac pacemaker, metal implants, claustrophobia, pregnancy)
Contraindications to either of the emergency medications (Ondansetron or Narcan)
History of head trauma
High blood pressure (>140 systolic, >90 diastolic)
History of impaired urinary elimination
Major kidney problems, bleeding problems, severe dehydration, or recovering from a recent surgery (within past year).
Instability of responses to experimental pain (see Study Procedures Section)
History of asthma
History of diabetes
Liver Function Test results greater than 2.5 times the upper limit of normal (ULN) at Screening
History of smoking (past or current)
Use of psychotropic drugs, hormone treatments (including hormonal birth control) within 1 year
Non-fluent speaker of English
Positive urine drug screen (i.e. positive on any of the 10 measures tested, including cocaine, marijuana, opiates, amphetamines, methamphetamines, phencyclidine, barbiturates, benzodiazepines, methadone, and tricyclic antidepressants)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Morphine condition	Integrated MR-PET scan	-
Ketorolac condition	Integrated MR-PET scan	-
Ketorolac condition	Ketorolac	-

Primary Outcome Measures

Name	Time	Method
fMRI Signal Changes	one day	Obtain information about brain activity, including BOLD (Blood-oxygen-level dependent) signal, using an fMRI system. Data analysis was applied using SPM 12 with a standard pipeline.
Pain Ratings	One day	The primary endpoint was the morphine and ketorolac conditioning effects as indicated by subjective pain rating changes between pain only (a control condition with no injection of glucose, but subject's did see an image of an hour glass displaying how much time they had before receiving a painful stimulus) and pain+glucose (subjects received a glucose injection accompanied by an injection schematic followed by a painful stimulus) within the morphine and ketorolac groups. We used the Gracely pain rating scale (ranging from 0, no sensation to 20, extremely painful).

Secondary Outcome Measures