Supra-additive effects of tramadol and acetaminophen in a human pain model
ABSTRACT The combination of analgesic drugs with different pharmacological properties may show better efficacy with less side effects. Aim of this study was to examine the analgesic and antihyperalgesic properties of the weak opioid tramadol and the non-opioid acetaminophen, alone as well as in combination, in an experimental pain model in humans. After approval of the local Ethics Committee, 17 healthy volunteers were enrolled in this double-blind and placebo-controlled study in a cross-over design. Transcutaneous electrical stimulation at high current densities (29.6+/-16.2 mA) induced spontaneous acute pain (NRS=6 of 10) and distinct areas of hyperalgesia for painful mechanical stimuli (pinprick-hyperalgesia). Pain intensities as well as the extent of the areas of hyperalgesia were assessed before, during and 150 min after a 15 min lasting intravenous infusion of acetaminophen (650 mg), tramadol (75 mg), a combination of both (325 mg acetaminophen and 37.5mg tramadol), or saline 0.9%. Tramadol led to a maximum pain reduction of 11.7+/-4.2% with negligible antihyperalgesic properties. In contrast, acetaminophen led to a similar pain reduction (9.8+/-4.4%), but a sustained antihyperalgesic effect (34.5+/-14.0% reduction of hyperalgesic area). The combination of both analgesics at half doses led to a supra-additive pain reduction of 15.2+/-5.7% and an enhanced antihyperalgesic effect (41.1+/-14.3% reduction of hyperalgesic areas) as compared to single administration of acetaminophen. Our study provides first results on interactions of tramadol and acetaminophen on experimental pain and hyperalgesia in humans. Pharmacodynamic modeling combined with the isobolographic technique showed supra-additive effects of the combination of acetaminophen and tramadol concerning both, analgesia and antihyperalgesia. The results might act as a rationale for combining both analgesics.
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ABSTRACT: Tramadol/paracetamol is a fixed-dose combination prescribed for the relief of moderate to severe pain. The combination acts synergistically and guarantees the rapid onset of paracetamol and the prolonged analgesic effect of tramadol with good tolerability. These drugs are often used in various formulations in the treatment of patients with postoperative pain, e.g. after stomach resection. Gastrectomy leads to pathophysiological changes within the alimentary tract, which may affect the process of drug absorption. The aim of the research was an analysis of the pharmacokinetics of tramadol/paracetamol from effervescent and conventional tablets in patients after total gastrectomy.Pharmacological reports: PR 02/2014; 66(1):159-164. DOI:10.1016/j.pharep.2013.06.010 · 2.17 Impact Factor
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ABSTRACT: Inguinal hernia repair is a very common surgical procedure that deserves performing in ambulatory setting. A comprehensive understanding of the local anatomy and of the surgical procedure is required to adequately adapt the regional anaesthetic technique. Several approaches are satisfactory, such as unilateral spinal anaesthesia, local anaesthetic instillation (for coelioscopic surgery), abdominal wall infiltration, ilio-inguinal, iliohypogastric block, transversus abdominis plane (TAP) block and paravertebral block. Ambulatory management of hernia repair also implies the prevention of urinary retention and postoperative nausea and vomiting.Le Praticien en Anesthésie Réanimation 06/2012; 16(3):167–176. DOI:10.1016/j.pratan.2012.06.003
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ABSTRACT: Noxious stimuli activate a complex cerebral network. During central sensitization to pain, activity in most of these areas is changed. One of these areas is the posterior parietal cortex (PPC). The role of the PPC during processing of acute pain as well as hyperalgesia and tactile allodynia remains elusive. Therefore, we performed a functional magnetic resonance imaging (fMRI) based, neuro-navigated, repetitive transcranial magnetic stimulation (rTMS) study in 10 healthy volunteers. Firstly, pin-prick hyperalgesia was provoked on the right volar forearm, using the model of electrically-induced secondary mechanical hyperalgesia. fMRI was performed during pin-prick stimulation inside and outside the hyperalgesic areas. Secondly, on four different experimental sessions, the left and right individual intraparietal BOLD peak-activations were used as targets for a sham-controlled 1 Hz rTMS paradigm of 10 min duration. We measured psychophysically the (i) electrical pain stimulus intensity on an 11-point numeric pain rating scale (NRS, 0–10), the (ii) area of hyperalgesia, and the (iii) area of dynamic mechanical allodynia. Sham stimulation or rTMS was performed 16 min after induction of pin-prick hyperalgesia and tactile allodynia. Compared to sham stimulation, no significant effect of rTMS was observed on pain stimulus intensity and the area of allodynia. However, a reduction of the hyperalgesic area was observed for rTMS of the left PPC (P<0.05). We discuss the role of the PPC in central sensitization to pain, in spatial discrimination of pain stimuli and in spatial-attention to pain stimuli.Neuroscience 10/2010; 170(2-170):670-677. DOI:10.1016/j.neuroscience.2010.07.024 · 3.33 Impact Factor