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| ID | Type | Description | Link |
|---|---|---|---|
| 2006-006847-30 | EudraCT Number |
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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.
Inclusion criteria :
In both groups:
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:
In "healthy" group:
- Any history of general anesthesia or surgery
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | 0,5 µg/kg |
|
| 2 | Experimental | 0,05 µg/kg |
|
| 3 | Experimental | 0,005 µg/kg |
|
| 4 | Placebo Comparator | NaCl 0,9 % |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fentanyl/Placebo injection | Drug | Ultra low dose intravenous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Non invasive blood pressure (SBP, DBP), heart rate, respiratory rate, pulse oxymetry and cognitive functions evaluation (sedation score). | all along the experimentation |
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Inclusion Criteria:
In both groups:
In "operated" group:
Exclusion Criteria:
In both groups:
In "healthy" group:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU de Bordeaux Département d'Anesthésie-Réanimation II | Pessac | Hôpital Cardiologique | 33604 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16129988 | Background | 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. | |
| 14527702 | 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. |
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| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
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| ID | Term |
|---|---|
| D005283 | Fentanyl |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| 11020770 | 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. |
| 16698416 | 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. |
| 11356895 | 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. |
| 7681556 | 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. |
| 1981160 | 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. |
| 9786023 | 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. |
| 15681961 | 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. |
| 10846153 | 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. |
| 11818772 | 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. |
| 12544821 | 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. |
| 29738328 | Result | 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. |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |