Tropisetron blocks analgesic action of acetaminophen: A human pain model study

被引:26
作者
Bandschapp, Oliver [1 ]
Filitz, Joerg [2 ]
Urwyler, Albert [1 ]
Koppert, Wolfgang [2 ]
Ruppen, Wilhelm [1 ]
机构
[1] Univ Basel, Univ Basel Hosp, Dept Anesthesia & Intens Care Med, CH-4031 Basel, Switzerland
[2] Univ Hosp Hannover, Dept Anesthesiol, Hannover, Germany
关键词
Interaction of acetaminophen and tropisetron; Serotonin antagonist; Central sensitization; Experimental pain; Hyperalgesia; HUMAN SKIN; ADMINISTERED PARACETAMOL; SEROTONERGIC SYSTEMS; C-NOCICEPTORS; RECEPTOR; RAT; ONDANSETRON; INHIBITION; MECHANISM; RELEASE;
D O I
10.1016/j.pain.2011.02.003
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Because the mechanism underlying the analgesic action of acetaminophen remains unclear, we investigated the possible interaction of acetaminophen with central serotonergic pathways. The effects of acetaminophen, tropisetron, the combination of both drugs, and saline on pain perception and central sensitization in healthy volunteers were compared. Sixteen healthy volunteers were included in this randomized, double-blind, placebo-controlled crossover study. Intracutaneous electrical stimulation (46.1 +/- 19.1 mA) induced acute pain (numeric rating scale, 6 of 10) and stable areas of hyperalgesia and allodynia. Pain intensities and areas of hyperalgesia and allodynia were regularly assessed before, during, and after a 15-min infusion of acetaminophen, tropisetron, the combination of both drugs, and saline. Acetaminophen concentrations were measured to rule out any pharmacokinetic interaction. Both acetaminophen and tropisetron led to decreased pain ratings as compared to saline. However, when acetaminophen and tropisetron were administered simultaneously, the pain ratings were not affected. There was no significant difference in the evolution of the hyperalgesic and allodynic areas during the study period between the study groups (P = .06 and P = .33, respectively). Acetaminophen serum levels were not significantly different when associated with tropisetron (P = .063), although we observed a trend toward lower acetaminophen concentrations when both drugs were concurrently administered. In summary, while the combination of acetaminophen and tropisetron showed no analgesic action, each drug administered alone led to decreased pain ratings as compared to saline. (C) 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1304 / 1310
页数:7
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共 50 条
[1]  
ALHAIDER AA, 1991, J NEUROSCI, V11, P1881
[2]   Tropisetron inhibits the antinociceptive effect of intrathecally administered paracetamol and serotonin [J].
Alloui, A ;
Pelissier, T ;
Dubray, C ;
Lavarenne, J ;
Eschalier, A .
FUNDAMENTAL & CLINICAL PHARMACOLOGY, 1996, 10 (04) :406-407
[3]   Ondansetron pretreatment to alleviate pain on propofol injection: A randomized, controlled, double blinded study [J].
Ambesh, SP ;
Dubey, PK ;
Sinha, PK .
ANESTHESIA AND ANALGESIA, 1999, 89 (01) :197-199
[4]   Characterization of the 5-HT4 binding site in human brain [J].
Arranz, B ;
Rosel, P ;
San, L ;
Sarró, S ;
Navarro, MA ;
Marcusson, J .
JOURNAL OF NEURAL TRANSMISSION, 1998, 105 (6-7) :575-586
[5]   PLASMA AND CEREBROSPINAL-FLUID CONCENTRATIONS OF PARACETAMOL AFTER A SINGLE INTRAVENOUS DOSE OF PROPACETAMOL [J].
BANNWARTH, B ;
NETTER, P ;
LAPICQUE, F ;
GILLET, P ;
PERE, P ;
BOCCARD, E ;
ROYER, RJ ;
GAUCHER, A .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1992, 34 (01) :79-81
[6]   Spinal 5-HT1A receptors differentially influence nociceptive processing according to the nature of the noxious stimulus in rats:: effect of WAY-100635 on the antinociceptive activities of paracetamol, venlafaxine and 5-HT [J].
Bonnefont, J ;
Chapuy, E ;
Clottes, E ;
Alloui, A ;
Eschalier, A .
PAIN, 2005, 114 (03) :482-490
[7]   Orally administered paracetamol does not act locally in the rat formalin test - Evidence for a supraspinal, serotonin-dependent antinociceptive mechanism [J].
Bonnefont, J ;
Alloui, A ;
Chapuy, E ;
Clottes, E ;
Eschalier, A .
ANESTHESIOLOGY, 2003, 99 (04) :976-981
[8]   A randomized controlled clinical trial of the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome [J].
Camilleri, M ;
Chey, WY ;
Mayer, EA ;
Northcutt, AR ;
Heath, A ;
Dukes, GE ;
McSorley, D ;
Mangel, AM .
ARCHIVES OF INTERNAL MEDICINE, 2001, 161 (14) :1733-1740
[9]   COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression [J].
Chandrasekharan, NV ;
Dai, H ;
Roos, KLT ;
Evanson, NK ;
Tomsik, J ;
Elton, TS ;
Simmons, DL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (21) :13926-13931
[10]   Effects of acetaminophen on monoaminergic systems in the rat central nervous system [J].
Courade, JP ;
Caussade, F ;
Martin, K ;
Besse, D ;
Delchambre, C ;
Hanoun, N ;
Hamon, M ;
Eschalier, A ;
Cloarec, A .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2001, 364 (06) :534-537