Modulation of Remifentanil-Induced Postinfusion Hyperalgesia
Summary
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.
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.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
Conditions
Hyperalgesia, Secondary
Intervention
Placebo, Remifentanil, Ketorolac and remifentanil, Parecoxib and remifentanil
Location
Ullevaal University Hospital
Oslo
Norway
0407
Status
Completed
Source
Ullevaal University Hospital
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00785863
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Hyperalgesia
An increased sensation to painful stimuli that may follow damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve. Hyperalgesia can occur both at the site of tissue damage (primary hyperalgesia) and in the surrounding undamaged areas (secondary hyperalgesia). (Kandel et al., Principles of Neural Science, 3d ed, p386)
Therapeutic Misconception
Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.
Ketorolac
A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed)
Ketorolac Tromethamine
A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity.
Placebo Effect
An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.
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