Hyperalgesia, Secondary Clinical Trial
Official title:
Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by Parecoxib or Ketorolac in Humans
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.
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.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
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