Modulation of Remifentanil-induced Postinfusion Hyperalgesia

Overview

In addition to alleviate pain there is growing evidence that µ-opioids enhance pain. This problem is known as opioid induced hyperalgesia(OIH).The NMDA receptor is involved in opioid induced hyperalgesia it may be possible to block OIH by cyclooxygenase inhibitors. This has been demonstrated with parecoxib, a COX-II inhibitor, in a experimental pain model.Both COX-1 and COX-2 are expressed in the spinal cord. It would be of interest to investigate whether a COX-1 preferring inhibitor like ketorolac also can reduce opioid induced hyperalgesic in this experimental pain model.

Full Title of Study: “Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by Parecoxib or Ketorolac in Humans”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Basic Science
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: April 2009

Detailed Description

Remifentanil is an fast acting opioid which has become very popular to use during surgery. There are studies, both experimental 1-3 and clinical 4;5, which indicate that remifentanil after end of infusion trigger enhanced pain experience and enhanced opioid consumption postoperatively. Therefore it is important to look at possibilities to block this enhanced pain experience (opioid induced hyperalgesia – OIH). Ketamin has demonstrated to block this effect 5;6 through the NMDA receptor. Unfortunately ketamin has some seriously side-effects like hallucinations, and is therefore not suitable in ordenary clinical use. Recently, it has been demonstrated that parecoxib (a COX-2 inhibitor) can prevent remifentanil-induced postinfusion hyperalgesia in a study on healthy volunteers.7 COX-2 inhibitors have some disadvantages because of the longterm adverse effects like cardiac arrest. Therefore it would be of interest to look at a COX-1 preferring NSAID, like ketorolac, to see if also non-selective NSAIDs can partly block remifentanil-induced postinfusion hyperalgesia. To investigate this and to provoke pain and secondary hyperalgesia we use an intradermal electrical pain model which is well established.1;7-9 Detailed description of this model look at reference 7. H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi.

Interventions

  • Other: Placebo
    • Placebo IV before placebo infusion
  • Drug: Remifentanil
    • placebo IV and remifentanil infusion
  • Drug: Ketorolac and remifentanil
    • Ketorolac IV and remifentanil infusion
  • Drug: Parecoxib and remifentanil
    • Parecoxib IV and remifentanil infusion

Arms, Groups and Cohorts

  • Placebo Comparator: Placebo
  • Active Comparator: Remifentanil
  • Active Comparator: Ketorolac and remifentanil
  • Active Comparator: Parecoxib and remifentanil

Clinical Trial Outcome Measures

Primary Measures

  • H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi.
    • Time Frame: during the study

Secondary Measures

  • HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi.
    • Time Frame: During the study

Participating in This Clinical Trial

Inclusion Criteria

  • Healthy volunteers Exclusion Criteria:

  • Allergy to the drugs used in the study

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Ullevaal University Hospital
  • Collaborator
    • University of Oslo
  • Provider of Information About this Clinical Study
    • Ullevaal University Hospital, Ullevaal University Hospital
  • Overall Official(s)
    • Harald Lenz, MD, Principal Investigator, Ullevaal University Hospital
    • Johan Raeder, Prof.,MD,PhD, Study Director, Ullevaal University Hospital
    • Audun Stubhaug, Prof.,MD,PhD, Study Director, Rikshospitalet University Hospital

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