Pain Prevention and Treatment Through the Enhancement of the Anti-nociceptive Component of Pain Modulation Profiles
Condition: Pain
Study type: Interventional

Summary: 
      To utilize the plasticity of the central pain pathways in order to (i) shift individuals with
      a pro-nociceptive pain modulation profile towards an anti-nociceptive one, and (ii) assess
      its relevance in minimizing pain-derived morbidity.
    

Detailed description: 
      In the project proposed here our main aim is to shift pain modulation towards
      anti-nociception as a novel approach to pain prevention and treatment. Our first hypothesis
      is that individual's modulation profile, when not anti-nociceptive, can be pharmacologically
      shifted into being anti-nociceptive. We assert (the first hypothesis) that such shift can be
      optimized by coupling the drug's mode of action with the individual's pain modulation
      profile; based on limited available data, it is suggested that less efficient inhibitory pain
      modulation will be modified best by serotonin-norepinephrine reuptake inhibitors (SNRIs),
      whereas enhanced facilitatory modulation will be modified best by Ca++ channel ligands. Pain
      modulation will be assessed by psychophysical tools, and will include dynamic tests of pain
      modulation. The conditioned pain modulation (CPM) test protocol will be used for assessing
      pain inhibition, and the temporal summation (TS) test protocol will be used for assessment of
      pain facilitation. Our second hypothesis is that SNRIs will be most efficacious in shifting
      individuals into being antinociceptive if these individuals had lower activation of the
      anterior brain pain network in the CPM test paradigm. In turn, Ca++ channel ligands will be
      most efficacious for individuals showing enhanced activation of the posterior pain network
      sites in response to the TS test protocol. Our third hypothesis is that an anti-nociceptive
      pain modulation profile protects individuals from acquiring pain. The model we chose for this
      study is surgery for coronary artery bypass grafting (CABG). Individuals scheduled for
      surgery, who are pain free, will be assigned to 3 arms - (1) duloxetine (DUL) (SNRI), (2)
      pregabalin (PGB) (Ca++ channel ligand) and (3) placebo. Drugs will be taken for 48 hours
      prior to surgery in a double-blind non cross-over parallel design. Pain modulation will be
      assessed before treatment, 2-4 hours prior to surgery and at its end, 6 weeks before surgery.
      Post operative acute and chronic pain will be assessed up to 2 month after surgery.
    

Intervention name(s): Duloxetine; Pregabalin; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): duloxetine 60mg; pregabalin 150mg; non active placebo
Intervention MeSH terms: Pregabalin; Duloxetine Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: endogenous pain modulation; coronary artery bypass grafting; quantitative sensory testings; duloxetine; pregabalin; preemptive treatment