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.

Inclusion Criteria:

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

Exclusion Criteria:

1. Current or past history of major medical, neurological, or psychiatric illness

2. 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)

3. 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

4. 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

5. Contraindications to fMRI scanning (including cardiac pacemaker, metal implants, claustrophobia, pregnancy)

6. Contraindications to either of the emergency medications (Ondansetron or Narcan)

7. History of head trauma

8. High blood pressure (>140 systolic, >90 diastolic)

9. History of impaired urinary elimination

10. Major kidney problems, bleeding problems, severe dehydration, or recovering from a recent surgery (within past year).

11. Instability of responses to experimental pain (see Study Procedures Section)

12. History of asthma

13. History of diabetes

14. Liver Function Test results greater than 2.5 times the upper limit of normal (ULN) at Screening

15. History of smoking (past or current)

16. Use of psychotropic drugs, hormone treatments (including hormonal birth control) within 1 year

17. Non-fluent speaker of English

18. 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)

Adverse event data was collected for each participant over a 3 hours period (from time of drug administration until they left 3 hours later). We collected this for every participant throughout our study.

Our definitions are consistent. After every drug administration we asked a standard questionnaire, which we also asked again a couple of hours following the initial drug administration. Specifically, we asked subjects if they felt nauseous, indigestion, itching, spacey/drugged, lightheadedness/faint, sense of difficulty concentrating, or sleepy.