Fentanyl Ultra Low Doses Effects on the Nociceptive Threshold

NCT00454259 | Completed Phase 4 DMC

• 2 other identifiers: CHUBX 2006/082006-006847-30
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pain, Postoperative

Keywords

Postoperative Hyperalgesia; Human volunteer; Fentanyl; Randomized Controlled Trial; Pain chronicisation; Predictive test

Outcome Measures

Primary Outcomes (1)

• Nociceptive threshold evaluated with sternal electronical Von Frey mechanical stimulation. The stimulation will increase until the volunteer presses a trigger when the stimulation becomes painful.

  5 min after injection, and every 15 min during 1 hour

Secondary Outcomes (1)

• Non invasive blood pressure (SBP, DBP), heart rate, respiratory rate, pulse oxymetry and cognitive functions evaluation (sedation score).

  all along the experimentation

Study Arms (4)

1

EXPERIMENTAL

0,5 µg/kg

Drug: Fentanyl/Placebo injection

2

EXPERIMENTAL

0,05 µg/kg

Drug: Fentanyl/Placebo injection

3

EXPERIMENTAL

0,005 µg/kg

Drug: Fentanyl/Placebo injection

4

PLACEBO COMPARATOR

NaCl 0,9 %

Drug: Fentanyl/Placebo injection

Interventions

Fentanyl/Placebo injection DRUG

Ultra low dose intravenous injection

1; 2; 3; 4

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In both groups:
• 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.

You may not qualify if:

• In both groups:
• 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
• Any contraindication to fentanyl use
• Use of any medication interacting with fentanyl
• In "healthy" group:
• Any history of general anesthesia or surgery

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (1)

CHU de Bordeaux Département d'Anesthésie-Réanimation II

Pessac, Hôpital Cardiologique, 33604, France

Location

Related Publications (13)

• Hsu YW, Somma J, Hung YC, Tsai PS, Yang CH, Chen CC. Predicting postoperative pain by preoperative pressure pain assessment. Anesthesiology. 2005 Sep;103(3):613-8. doi: 10.1097/00000542-200509000-00026.

  PMID: 16129988 BACKGROUND

• Kalkman JC, Visser K, Moen J, Bonsel JG, Grobbee ED, Moons MKG. Preoperative prediction of severe postoperative pain. Pain. 2003 Oct;105(3):415-423. doi: 10.1016/S0304-3959(03)00252-5.

  PMID: 14527702 BACKGROUND

• Perkins FM, Kehlet H. Chronic pain as an outcome of surgery. A review of predictive factors. Anesthesiology. 2000 Oct;93(4):1123-33. doi: 10.1097/00000542-200010000-00038. No abstract available.

  PMID: 11020770 BACKGROUND

• Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.

  PMID: 16698416 BACKGROUND

• Celerier E, Laulin JP, Corcuff JB, Le Moal M, Simonnet G. Progressive enhancement of delayed hyperalgesia induced by repeated heroin administration: a sensitization process. J Neurosci. 2001 Jun 1;21(11):4074-80. doi: 10.1523/JNEUROSCI.21-11-04074.2001.

  PMID: 11356895 BACKGROUND

• Coderre TJ, Katz J, Vaccarino AL, Melzack R. Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain. 1993 Mar;52(3):259-285. doi: 10.1016/0304-3959(93)90161-H.

  PMID: 7681556 BACKGROUND

• Shen KF, Crain SM. Cholera toxin-B subunit blocks excitatory effects of opioids on sensory neuron action potentials indicating that GM1 ganglioside may regulate Gs-linked opioid receptor functions. Brain Res. 1990 Oct 29;531(1-2):1-7. doi: 10.1016/0006-8993(90)90751-v.

  PMID: 1981160 BACKGROUND

• Crain SM, Shen KF. Modulation of opioid analgesia, tolerance and dependence by Gs-coupled, GM1 ganglioside-regulated opioid receptor functions. Trends Pharmacol Sci. 1998 Sep;19(9):358-65. doi: 10.1016/s0165-6147(98)01241-3.

  PMID: 9786023 BACKGROUND

• Richebe P, Rivat C, Laulin JP, Maurette P, Simonnet G. Ketamine improves the management of exaggerated postoperative pain observed in perioperative fentanyl-treated rats. Anesthesiology. 2005 Feb;102(2):421-8. doi: 10.1097/00000542-200502000-00028.

  PMID: 15681961 BACKGROUND

• Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000 Jun 9;288(5472):1765-9. doi: 10.1126/science.288.5472.1765.

  PMID: 10846153 BACKGROUND

• Rivat C, Laulin JP, Corcuff JB, Celerier E, Pain L, Simonnet G. Fentanyl enhancement of carrageenan-induced long-lasting hyperalgesia in rats: prevention by the N-methyl-D-aspartate receptor antagonist ketamine. Anesthesiology. 2002 Feb;96(2):381-91. doi: 10.1097/00000542-200202000-00025.

  PMID: 11818772 BACKGROUND

• Simonnet G, Rivat C. Opioid-induced hyperalgesia: abnormal or normal pain? Neuroreport. 2003 Jan 20;14(1):1-7. doi: 10.1097/00001756-200301200-00001. No abstract available.

  PMID: 12544821 BACKGROUND

• Richebe P, Capdevila X, Rivat C. Persistent Postsurgical Pain: Pathophysiology and Preventative Pharmacologic Considerations. Anesthesiology. 2018 Sep;129(3):590-607. doi: 10.1097/ALN.0000000000002238.

  PMID: 29738328 RESULT

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Fentanyl

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Philippe RICHEBE, Dr

  University Hospital, Bordeaux

  STUDY DIRECTOR

• Gérard JANVIER, PHD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Claude DUBRAY, PHD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Alain ESCHALIER, PHD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• jean DUALE CHRISTIAN, Dr

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Gisèle PICKERING, Dr

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2007
• First Posted: March 30, 2007
• Study Start: March 1, 2007
• Primary Completion: August 1, 2007
• Study Completion: August 1, 2007
• Last Updated: May 14, 2026

Record last verified: 2007-03

Locations

FR (1)