Shifting pain modulation towards anti-nociceptivity: Mechanism-specific pharmacological prevention of post sternotomy pain: the MASTER study

INTERVENTION: Trade Name: Cymbalta Pharmaceutical Form: Capsule Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use Trade Name: Lyrica Pharmaceutical Form: Capsule Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use CONDITION: chronic pain Therapeutic area: Body processes [G] ‐ Physiological processes [G07] SECONDARY OUTCOME: Secondary end point(s): Consumption of analgesics; Pain assessment Timepoint(s) of evaluation of this end point: Postoperative (up to one year postoperative) INCLUSION CRITERIA: Patients of either sex with American Society of Anesthesiologists score 1, 2 or 3, aged 18 to 70 years planned to undergo elective surgery involving a sternotomy may be enrolled in the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 290 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10 PRIMARY OUTCOME: Main Objective: In this research project we explore anti‐nociception as a state of pain modulation. Our main objectives in utilizing the plasticity of the central pain pathways are to: ; (i) Shift individuals from a pro‐nociceptive pain modulation profile to an anti‐nociceptive profile;; (ii) Explore how this affects their chances of developing chronic pain; and ; (iii) Explore whether a pharmacologically induced shift towards an anti‐nociceptive state is efficient in the prevention of chronic postoperative pain. Primary end point(s): Psychophysical assessments: temporal summation (TS) and conditioned pain modulation (CPM); Psychological assessments: anxiety level (Spielberger State‐Trait Anxiety Inventory), pain catastrophizing (Pain Catastrophizing Scale), the Big Five Inventory, Hospital Anxiety and Depression Score; Pain assessment at rest and during coughing (pain numerical rating scores) Secondary Objective: Specific aim (SA) 1: To explore the transition from pro‐nociception to anti‐nociception by augmenting pain inhibition or attenuating pain facilitation.; SA 2: To explore whether a mechanism‐specific shift of a pain modulatory profile (PMP) from pro‐ to anti‐nociception yields better preemptive analgesia then mechanism non‐specific one. ; SA 3: To explore whether pharmacologically induced shift from pro‐ to anti‐nociception is as effective as innate anti‐nociception in lowering post‐operative pain. ; Additional points that could potentially be addressed by the proposed study, but will not be defined as specific aims, will include the question of the relative weight of shift to anti‐nociception based on the inhibitory line compared to that based on the facilitatory line. ; We would also be interested to assess the effect of the non‐specific effects of the study drugs. This is since these drugs have modes of action additional to their primary one, which might play a significant role. Timepoint(s) of evaluation of this end point: Pre‐operative (day ‐14); Pre‐operative (day ‐1); Post‐operative (days 3‐5)