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

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.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Duloxetine; Drug: Placebo; Drug: Pregabalin

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel
    • Rambam Health Care Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes in pain response after administration of duloxetine and pregabalin	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.	3 years

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: December 18, 2013
• First Submitted That Met QC Criteria: December 18, 2013
• First Posted (Estimate): December 24, 2013

Study Record Updates

• Last Update Posted (Actual): October 4, 2017
• Last Update Submitted That Met QC Criteria: October 1, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: pregabalin; endogenous pain modulation; duloxetine; coronary artery bypass grafting; preemptive treatment; quantitative sensory testings
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Anti-Anxiety Agents; Anticonvulsants; Serotonin and Noradrenaline Reuptake Inhibitors; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Duloxetine Hydrochloride; Pregabalin
• Other Study ID Numbers: 0472-13-RMB.CTIL