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Pain Prevention and Treatment Through the Enhancement of the Anti-nociceptive Component of Pain Modulation Profiles

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02020122
Recruitment Status : Completed
First Posted : December 24, 2013
Last Update Posted : October 4, 2017
Information provided by (Responsible Party):
d_yarnitsky, Rambam Health Care Campus

Brief 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.

Condition or disease Intervention/treatment Phase
Pain Drug: Duloxetine Drug: Pregabalin Drug: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Actual Study Start Date : January 2014
Actual Primary Completion Date : January 2015
Actual Study Completion Date : January 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Duloxetine
DUL 60mg x once a day x 2 days. This arm will also take 2 non-active placebo x once a day x 2 days
Drug: Duloxetine
duloxetine 60mg

Drug: Placebo
non active placebo

Active Comparator: Pregabalin
PGB 150mg x twice a day x 2 days
Drug: Pregabalin
pregabalin 150mg

Placebo Comparator: Placebo
Non active placebo x twice a day x 2 days
Drug: Placebo
non active placebo

Primary Outcome Measures :
  1. The changes in pain response after administration of duloxetine and pregabalin [ Time Frame: 3 years ]
    The changes in the excitatory and inhibitory pain modulation responses (assessed by temporal summation and conditioned pain modulation) will be examined before and after the administration of duloxetine and pregabalin in the set of pre and post coronary artery bypass grafting surgery.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Otherwise healthy, age 18-75.

Exclusion Criteria:

  • Regular use of analgesia for any purpose, including SNRIs, gabapentins, COX inhibitors.
  • Presence of diagnosed chronic pain disorders, psychiatric disorders, cognitive and /or neurological deficit.
  • Inability to give informed consent, communicate and understand the purpose and instructions of this study.
  • Pregnant or nursing women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02020122

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Rambam Health Care Campus
Haifa, Israel
Sponsors and Collaborators
Rambam Health Care Campus
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Principal Investigator: David Yarnitsky, Professor Rambam Health Care Campus
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Responsible Party: d_yarnitsky, Professor, Head of Neurology Deapartment, Rambam Health Care Campus Identifier: NCT02020122    
Other Study ID Numbers: 0472-13-RMB.CTIL
First Posted: December 24, 2013    Key Record Dates
Last Update Posted: October 4, 2017
Last Verified: October 2017
Keywords provided by d_yarnitsky, Rambam Health Care Campus:
endogenous pain modulation
coronary artery bypass grafting
quantitative sensory testings
preemptive treatment
Additional relevant MeSH terms:
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Duloxetine Hydrochloride
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Antidepressive Agents
Dopamine Agents