A study to investigate the effects of two painkillers as a combination treatment for pain

Analgesic effects measured using the following pre-dose up to 9 h post-dose:
1. Pressure Pain: Pain Detection Threshold (PDT), Pain Tolerance Threshold (PTT), Area Under the Curve (AUC), post-test Visual Analogue Scale (VAS)
2. Heat pain (pre-cold pressor: unexposed/normal and UVB-exposed skin, the latter only for subjects with MED lower than 355 mJ/cm² at screening): PDT, and post-test VAS.
3. Cold Pressor: PDT, PTT, Area Above the Curve (AAC), post-test VAS
4. Electrical Stair test: PDT, PTT, AUC, post-test VAS
5. Electrical burst test: PDT, PTT, AUC, post-test VAS
6. Conditioned Pain Modulation (CPM) Response (change from heat pain pre-and post-cold pressor): PDT
7. Short Form McGill Pain Questionnaire (SFMPQ) for pressure pain, heat pain, cold pressor, electrical stair test and electrical burst test.

To evaluate the drug-sensitive central nervous system (CNS) functioning of morphine, pregabalin and the two drugs as combination by biomarker profiling and the NeuroCart at pre-dose up to 9 h post-dose:
1. Body sway: antero-posterior sway (mm);
2. Visual Analog Scales (VAS) according to Bond and Lader to assess:
2.1. mood (mm),
2.2. alertness (mm), and
2.3. calmness (mm).
3. Visual Analog Scales (VAS) according to Bowdle to assess:
3.1. Feeling high (mm)
3.2. Internal perception (mm)
3.3. External perception(mm)
4. N-back
4.1. Average reaction time (ms) (zero-, one-, two-back)
4.2. Number of correct targets (zero-, one-, two-back)
4.3. Number of incorrect targets (zero-, one-, two-back)
4.4. Number of faulty non-target responses (zero-, one-, two-back)
5. Adaptive Tracking: Average performance (%);
6. Visual Verbal Learning Test (VVLT) memory testing
6.1. Immediate recall trial 3 (number correct)
6.2. Delayed recall (number correct)
6.3. Delayed recognition (number correct)
6.4. Delayed recognition (reaction time correct) (msec)
7. Electroencephalography: Frequency ranges for spectral analysis, Delta, Theta, Alpha, Beta, Gamma
8. Simple Reaction Time Task (SRT): Reaction time (ms) Questionnaires:
9. State-Trait Anxiety Inventory (STAI): State anxiety score
10. Brief Symptom Inventory (BSI)
10.1 General somatic symptoms
10.2 Cognitive symptom so Inter personal sensitivity
10.3 Depressed mood
10.4 Anxiety
10.5 Hostility
10.6 Phobic anxiety
10.7 Paranoid thoughts
10.8 Psychoticism
10.9 Global severity index

To evaluate the blood pharmacokinetic parameters of morphine, pregabalin and the two drugs as a combination at pre-dose up to 24h post-dose:
11. PK parameters of morphine (and metabolitemorphine-6-glucuronide), pregabalin by noncompartmental analysis of the plasma concentration-time data: AUCinf, AUClast, CL(/F), Cmax, t1/2, tlag, tmax, Vz(/F)

To evaluate the safety and tolerability of morphine, pregabalin and the two drugs as combination at Day-1 up to the follow-up visit:
12. Treatment-emergent (serious) adverse events ((S)AEs)throughout the study at every study visit
13. Concomitant medication throughout the study at every study visit
14. Vital signs (Pulse Rate (bpm), Systolic blood pressure (mmHg),Oxygen saturation, Diastolic blood pressure (mmHg)) as per assessment schedule
15. Clinical laboratory tests(Hematology, blood chemistry, glucose, and urinalysis)as per assessment schedule
16. ECG parameters (Heart Rate (HR) (bpm), PR, QRS, QT, QTcF) as per assessment schedule