Fentanyl Ultra Low Doses Effects on the Nociceptive Threshold
Condition: Pain, Postoperative
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      Exaggerated pain and hyperalgesia are major issues after surgery and can lead to chronic
      pain. Opioid are parts of pain sensitization processes but remain absolutely necessary in the
      intraoperative period. NMDA receptor antagonists succeed in reducing this pain sensitization
      process. Recent studies show that in pain and opioid-experienced rats (POER) fentanyl ultra
      low doses do not induce analgesia, as observed in naive rats, but hyperalgesia. This is the
      first demonstration that a drug can induce opposite effect depending on individual history.
      We also observed a strong correlation between this hyperalgesic response in POER and the
      intensity of hyperalgesia they develop later, after inflammatory or surgical pain. The main
      aim of this study is to measure the dose effect response to fentanyl "ultra low doses" on
      human volunteer's nociceptive threshold, to determine if such an opposite response profile
      can be revealed.
    

Detailed description: 
      -  Principal Objective : "Evaluate fentanyl "ultra low doses" effects on human volunteer's
           nociceptive threshold depending on their prior pain and opioid experience."

        -  Secondary Objective : "Confirm the innocuousness of this test (the 3 "ultra low doses"
           used in this trial will be 10 to 1,000 fold lower than low doses use for anesthesia and
           analgesia) and to find the fentanyl ultra low dose that could be used to develop a pain
           sensitisation predictive test."

        -  Study design : Bicentric, prospective, randomized, double-blind study.

      Inclusion criteria :

      In both groups:

        -  18-40 years old male volunteer

        -  weight: 60 to 85 kg

        -  ASA score: 1

        -  Informed consent obtained from the patient

        -  Gender : Male

      In "operated" group:

      - At least one history of peripheral surgery under general anesthesia with opioid in the past
      five years

      Exclusion criteria :

      In both groups:

        -  The patient do not accept inclusion to the study

        -  Drug or alcohol abuse history

        -  Chronic use of analgesic drugs or history of chronic pain

        -  Analgesic or opioid consumption within the 12hs preceding the fentanyl or placebo
           injection

        -  Neurological and/or psychiatric disorder, inability to give informed consent

        -  Psychological trauma within the two year preceding the inclusion

        -  Any contraindication to fentanyl use

        -  Use of any medication interacting with fentanyl

        -  Exclusion period from the national healthy volunteer register

        -  Gender : Female

      In "healthy" group:

      - Any history of general anesthesia or surgery

        -  Study plan: comparing two groups that only defer by their surgical and opioid prior
           experience and will receive three fentanyl ultra low doses (10 to 1,000 fold lower than
           low doses use for anesthesia and analgesia) and placebo (cross over administration, one
           week wash out period).

        -  Number of subjects : 48
    

Intervention name(s): Fentanyl/Placebo injection
Intervention type(s): Drug
Intervention description(s): Ultra low dose intravenous injection
Intervention MeSH terms: Fentanyl
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Health Services Research
Keywords: Postoperative Hyperalgesia; Human volunteer; Fentanyl; Randomized Controlled Trial; Pain chronicisation; Predictive test