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

Study Overview
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Brief Summary
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Healthy right-handed volunteers aged 21 to 50 needed for a research study of the effects of morphine and ketorolac on brain activity in response to pain stimuli as measured by functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET). Study will be conducted on six separate days not requiring an overnight stay in the hospital.

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

Conditions
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Healthy Controls

Intervention / Treatment
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* Radiation: Integrated MR-PET scan
* Drug: Ketorolac


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Morphine condition<br> | Radiation: Integrated MR-PET scan<br>* Integrated MR-PET scan using [11C]diprenorphine<br>|
| Experimental: Ketorolac condition<br> | Radiation: Integrated MR-PET scan<br>* Integrated MR-PET scan using [11C]diprenorphine<br>Drug: Ketorolac<br>* 3 administrations of ketorolac over course of study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fMRI Signal Changes | 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. | one day | 
| Pain Ratings | 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). | One day |