Fentanyl Ultra Low Doses Effects on the Nociceptive Threshold

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.

* 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

Eligibility Criteria:
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

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 patients 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

In "healthy" group:

* Any history of general anesthesia or surgery