Summary: A narcotic analgesic proposed for severe pain. It may be habituating.

Top Publications

  1. Mitra S, Khandelwal P, Sehgal A. Diclofenac-tramadol vs. diclofenac-acetaminophen combinations for pain relief after caesarean section. Acta Anaesthesiol Scand. 2012;56:706-11 pubmed publisher
    We compared the analgesic efficacy of diclofenac-acetaminophen combination with diclofenac-tramadol combination to optimize multimodal post-operative analgesia in women undergoing caesarean section.
  2. Singh I, Kumar P, Kumar S, Rana V. Formulation and development of matrix tablets of tramadol using katira gum as release modifier. Yakugaku Zasshi. 2010;130:1225-31 pubmed
    ..The present study was aimed to study the drug release retardant property of katira gum in matrix tablets containing tramadol as a model drug. Katira gum was characterized in terms of pH, viscosity and swelling index...
  3. Lin T, Lin F, Chou W, Yeh Y, Lin C, Fan S, et al. Compatibility and stability of binary mixtures of ketorolac tromethamine and tramadol hydrochloride injection concentrate and diluted infusion solution. Acta Anaesthesiol Taiwan. 2010;48:117-21 pubmed publisher
    Ketorolac added to tramadol as an injection mixture convenient for clinical use has been shown to be an effective balanced analgesic regimen in alleviating moderate-to-severe pain...
  4. Ugur K, Karabayirli S, Demircioglu R, Ark N, Kurtaran H, Muslu B, et al. The comparison of preincisional peritonsillar infiltration of ketamine and tramadol for postoperative pain relief on children following adenotonsillectomy. Int J Pediatr Otorhinolaryngol. 2013;77:1825-9 pubmed publisher
    To investigate and compare the effectiveness of preincisional peritonsillar infiltration of ketamine and tramadol for post-operative pain on children following adenotonsillectomy.
  5. Brattwall M, Turan I, Jakobsson J. Pain management after elective hallux valgus surgery: a prospective randomized double-blind study comparing etoricoxib and tramadol. Anesth Analg. 2010;111:544-9 pubmed publisher
    ..In the present prospective, randomized, double-blind study we compared pain management with a selective (COX-2) inhibitor (etoricoxib) with pain management using sustained-release tramadol after elective hallux valgus surgery.
  6. Karabayirli S, Ayrım A, Muslu B. Comparison of the analgesic effects of oral tramadol and naproxen sodium on pain relief during IUD insertion. J Minim Invasive Gynecol. 2012;19:581-4 pubmed publisher
    To compare the analgesic efficacy of oral tramadol and naproxen sodium on pain during insertion of an intrauterine device (IUD).
  7. Elkalioubie A, Allorge D, Robriquet L, Wiart J, Garat A, Broly F, et al. Near-fatal tramadol cardiotoxicity in a CYP2D6 ultrarapid metabolizer. Eur J Clin Pharmacol. 2011;67:855-8 pubmed publisher
    b>Tramadol is a synthetic, centrally acting analgesic for the treatment of moderate to severe pain...
  8. Pergolizzi J, Taylor R, Raffa R. Extended-release formulations of tramadol in the treatment of chronic pain. Expert Opin Pharmacother. 2011;12:1757-68 pubmed publisher
    b>Tramadol is a centrally acting analgesic available throughout the world...
  9. Matkap E, Bedirli N, Akkaya T, Gumus H. Preincisional local infiltration of tramadol at the trocar site versus intravenous tramadol for pain control after laparoscopic cholecystectomy. J Clin Anesth. 2011;23:197-201 pubmed publisher
    To compare the effects of preoperative intravenous (IV) tramadol and preoperative tramadol infiltration of trocar sites on postoperative pain and postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy.

More Information


  1. Tuncer S, Aysolmaz G, Reisli R, Erol A, Yalcin N, Yosunkaya A. [The effects of the administration of subfacial levobupivacaine infusion with the ON-Q pain pump system on postoperative analgesia and tramadol consumption in cesarean operations]. Agri. 2010;22:73-8 pubmed
    In this study, the effects of administration of subfacial levobupivacaine infusion with the ON-Q pain pump system were investigated in elective cesarean operations for postoperative pain control and tramadol-sparing effect.
  2. Sawynok J, Reid A, Liu J. Spinal and peripheral adenosine A? receptors contribute to antinociception by tramadol in the formalin test in mice. Eur J Pharmacol. 2013;714:373-8 pubmed publisher
    b>Tramadol, an analgesic used alone or combined with acetaminophen, has a complex mechanism of action involving opioid and amine mechanisms...
  3. Nagakannan P, Shivasharan B, Thippeswamy B, Veerapur V. Effect of tramadol on behavioral alterations and lipid peroxidation after transient forebrain ischemia in rats. Toxicol Mech Methods. 2012;22:674-8 pubmed publisher
    ..b>Tramadol, a centrally acting opioid analgesic reportedly possesses NMDA antagonistic and GABA agonistic properties, with ..
  4. Rúa Gómez P, Püttmann W. Impact of wastewater treatment plant discharge of lidocaine, tramadol, venlafaxine and their metabolites on the quality of surface waters and groundwater. J Environ Monit. 2012;14:1391-9 pubmed publisher
    The presence of the anesthetic lidocaine (LDC), the analgesic tramadol (TRA), the antidepressant venlafaxine (VEN) and the metabolites O-desmethyltramadol (ODT) and O-desmethylvenlafaxine (ODV) was investigated in wastewater treatment ..
  5. da Costa Araújo F, de Santana Santos T, de Morais H, Laureano Filho J, de Oliveira e Silva E, Vasconcellos R. Comparative analysis of preemptive analgesic effect of tramadol chlorhydrate and nimesulide following third molar surgery. J Craniomaxillofac Surg. 2012;40:e346-9 pubmed publisher
    ..paired trial was to perform a comparative analysis of the preemptive analgesic effect of nimesulide and tramadol chlorhydrate during third molar surgery...
  6. Mejjad O, Serrie A, Ganry H. Epidemiological data, efficacy and safety of a paracetamol-tramadol fixed combination in the treatment of moderate-to-severe pain. SALZA: a post-marketing study in general practice. Curr Med Res Opin. 2011;27:1013-20 pubmed publisher
    To evaluate the efficacy and safety of the paracetamol-tramadol combination (PTC) in treating moderate-to-severe pain, in patients aged 65 years and over within general practitioner (GP) practice centers.
  7. Farshchi A, Ghiasi G. Comparison the analgesic effects of single dose administration of tramadol or piroxicam on postoperative pain after cesarean delivery. Acta Med Iran. 2010;48:148-53 pubmed
    ..pain in a double-blinded, randomized, single-dose comparison of the monoaminergic and mu-opioid agonist tramadol, 100 mg (Group T) and piroxicam 20 mg (Group P) given IM alone--single dose in 150 patients who had elective ..
  8. Cannon C, Kissling G, Hoenerhoff M, King Herbert A, Blankenship Paris T. Evaluation of dosages and routes of administration of tramadol analgesia in rats using hot-plate and tail-flick tests. Lab Anim (NY). 2010;39:342-51 pubmed publisher
    b>Tramadol is an opioid-like analgesic with relatively mild side effects...
  9. Ko S, Kwon H, Yu J, Baik S, Park I, Lee J, et al. Comparison of the efficacy and safety of tramadol/acetaminophen combination therapy and gabapentin in the treatment of painful diabetic neuropathy. Diabet Med. 2010;27:1033-40 pubmed publisher
    This study compared the efficacy and safety of tramadol/acetaminophen (T/A) and gabapentin in the management of painful diabetic neuropathy.
  10. Wagner R, Piler P, Bedanova H, Adamek P, Grodecka L, Freiberger T. Myocardial injury is decreased by late remote ischaemic preconditioning and aggravated by tramadol in patients undergoing cardiac surgery: a randomised controlled trial. Interact Cardiovasc Thorac Surg. 2010;11:758-62 pubmed publisher in coronary artery bypass grafting (CABG) with cold-crystalloid cardioplegia and whether preoperative tramadol modifies myocardial ischaemia-reperfusion injury using the same group of patients in a single-blinded randomized ..
  11. Pandey R, Elakkumanan L, Garg R, Gupta P, Darlong V, Punj J. Prolonged apnea after small single dose of intravenous tramadol. AANA J. 2010;78:110-2 pubmed
    We report an unusual case of respiratory depression and prolonged apnea after a single, 50-mg intravenous dose of tramadol. Shortly after an uneventful surgery and anesthesia, the patient was administered intravenous tramadol...
  12. Barros A, Vale C, Oliveira F, Ventura C, Assunção J, Fontes Ribeiro C, et al. Dexamethasone effect on postoperative pain and tramadol requirement after thyroidectomy. Pharmacology. 2013;91:153-7 pubmed publisher
    b>Tramadol is a central-acting analgesic associated with nausea and vomiting. Clinical studies have demonstrated that glucocorticoids have analgesic and antiemetic effects when administered perioperatively...
  13. Afkhami A, Ghaedi H, Madrakian T, Ahmadi M, Mahmood Kashani H. Fabrication of a new electrochemical sensor based on a new nano-molecularly imprinted polymer for highly selective and sensitive determination of tramadol in human urine samples. Biosens Bioelectron. 2013;44:34-40 pubmed publisher
    ..The electrode was applied to the simple, rapid, highly selective and sensitive determination of tramadol using square wave voltammetry...
  14. Lanier R, Lofwall M, Mintzer M, Bigelow G, Strain E. Physical dependence potential of daily tramadol dosing in humans. Psychopharmacology (Berl). 2010;211:457-66 pubmed publisher
    b>Tramadol is an atypical, mixed-mechanism analgesic involving both opioid and catecholamine processes that appears to have low abuse potential and may be useful as a treatment for opioid dependence.
  15. Leppert W, Majkowicz M. The impact of tramadol and dihydrocodeine treatment on quality of life of patients with cancer pain. Int J Clin Pract. 2010;64:1681-7 pubmed publisher
    b>Tramadol and dihydrocodeine (DHC) are analgesics of step 2 WHO analgesic ladder (opioids for mild to moderate pain, weak opioids) frequently used in the treatment of cancer pain of moderate intensity...
  16. Barber J. Examining the use of tramadol hydrochloride as an antidepressant. Exp Clin Psychopharmacol. 2011;19:123-30 pubmed publisher
    b>Tramadol (Ultram, Ultracet) is a centrally acting synthetic opioid with analgesic efficacy comparable to codeine...
  17. Miranda H, Noriega V, Zepeda R, Sierralta F, Prieto J. Synergism between fentanyl and tramadol in tonic inflammatory pain: the orofacial formalin test. Inflammation. 2012;35:1132-7 pubmed publisher
    ..present study was conducted to determine the antinociceptive interaction between the dual mechanism of action of tramadol compared to the main of fentanyl antinociception in the orofacial formalin which represents a model of persistent ..
  18. Akbay B, Yildizbas S, Guclu E, Yilmaz S, Iskender A, Ozturk O. Analgesic efficacy of topical tramadol in the control of postoperative pain in children after tonsillectomy. J Anesth. 2010;24:705-8 pubmed publisher
    ..Therefore, this study was conducted to evaluate the effects of topical tramadol on postoperative pain and morbidity in children undergoing tonsillectomy.
  19. Zhang M, Jing L, Liu Q, Wen R, Li J, Li Y, et al. Tramadol induces conditioned place preference in rats: interactions with morphine and buprenorphine. Neurosci Lett. 2012;520:87-91 pubmed publisher
    Surveys and drug surveillance have demonstrated that the abuse liability of tramadol is considerably low in the general population but appears to be higher in opiate addicts, and this difference could attribute to the poly-drug abuse of ..
  20. Martins T, Kahvegian M, Noel Morgan J, Leon Roman M, Otsuki D, Fantoni D. Comparison of the effects of tramadol, codeine, and ketoprofen alone or in combination on postoperative pain and on concentrations of blood glucose, serum cortisol, and serum interleukin-6 in dogs undergoing maxillectomy or mandibulectomy. Am J Vet Res. 2010;71:1019-26 pubmed publisher
    To compare analgesic effects of tramadol, codeine, and ketoprofen administered alone and in combination and their effects on concentrations of blood glucose, serum cortisol, and serum interleukin (IL)-6 in dogs undergoing maxillectomy or ..
  21. Duke A, Bigelow G, Lanier R, Strain E. Discriminative stimulus effects of tramadol in humans. J Pharmacol Exp Ther. 2011;338:255-62 pubmed publisher
    b>Tramadol is an unscheduled atypical analgesic that acts as an agonist at ?-opioid receptors and inhibits monoamine reuptake...
  22. Bloms Funke P, Dremencov E, Cremers T, Tzschentke T. Tramadol increases extracellular levels of serotonin and noradrenaline as measured by in vivo microdialysis in the ventral hippocampus of freely-moving rats. Neurosci Lett. 2011;490:191-5 pubmed publisher
    b>Tramadol is an atypical opioid with monoamine re-uptake inhibition properties...
  23. Tzvetkov M, Saadatmand A, Lotsch J, Tegeder I, Stingl J, Brockmoller J. Genetically polymorphic OCT1: another piece in the puzzle of the variable pharmacokinetics and pharmacodynamics of the opioidergic drug tramadol. Clin Pharmacol Ther. 2011;90:143-50 pubmed publisher
    We investigated whether tramadol or its active metabolite, O-desmethyltramadol, are substrates of the organic cation transporter OCT1 and whether polymorphisms in OCT1 affect tramadol and O-desmethyltramadol pharmacokinetics...
  24. Zhang J, Wu D, Xie C, Wang H, Wang W, Zhang H, et al. Tramadol and propentofylline coadministration exerted synergistic effects on rat spinal nerve ligation-induced neuropathic pain. PLoS ONE. 2013;8:e72943 pubmed publisher
    Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons...
  25. Eichhorn A, Barth J. [Chronic dizziness in a pain patient--pharmacogenomic identification of tramadol as cause]. Rehabilitation (Stuttg). 2010;49:393-5 pubmed publisher
    This casuistic reports on a 59-year-old pain patient taking normal dosage Tramadol as analgetic drug, who suffered from chronic dizziness leading to immobilisation for more than 9 months...
  26. Neri E, Maestro A, Minen F, Montico M, Ronfani L, Zanon D, et al. Sublingual ketorolac versus sublingual tramadol for moderate to severe post-traumatic bone pain in children: a double-blind, randomised, controlled trial. Arch Dis Child. 2013;98:721-4 pubmed publisher
    To assess the effectiveness of sublingual ketorolac versus sublingual tramadol in reducing the pain associated with fracture or dislocation of extremities in children.
  27. Mei X, Chen L, Wang W, Wu D, Wang L, Zhang T, et al. Combination of tramadol with minocycline exerted synergistic effects on a rat model of nerve injury-induced neuropathic pain. Neurosignals. 2013;21:184-96 pubmed publisher
    Neuropathic pain is a refractory clinical problem. Certain drugs, such as tramadol, proved useful for the treatment of neuropathic pain by inhibiting the activity of nociceptive neurons...
  28. Spagnoli A, Rizzo M, Palmieri A, Sorvillo V, Quadrini L, Scuderi N. A single blind controlled comparison of tramadol/paracetamol combination and paracetamol in hand and foot surgery. A prospective study. In Vivo. 2011;25:291-5 pubmed
    The objective of this study was to compare the efficacy and effectiveness between an analgesic combination of tramadol/paracetamol (37...
  29. Slanar O, Dupal P, Matouskova O, Vondrácková H, Pafko P, Perlik F. Tramadol efficacy in patients with postoperative pain in relation to CYP2D6 and MDR1 polymorphisms. Bratisl Lek Listy. 2012;113:152-5 pubmed
    The aim of our study was to evaluate impact of CYP2D6 and MDR1 polymorphisms on the analgesic efficacy of tramadol in patients after a knee arthroscopy.
  30. Coller J, Michalakas J, James H, Farquharson A, Colvill J, White J, et al. Inhibition of CYP2D6-mediated tramadol O-demethylation in methadone but not buprenorphine maintenance patients. Br J Clin Pharmacol. 2012;74:835-41 pubmed publisher
    ..Hence there is a need to find alternative analgesics to classical opioids and tramadol is potentially one such alternative. Methadone inhibits CYP2D6 in vivo and in vitro...
  31. Bigham A, Habibian S, Ghasemian F, Layeghi S. Caudal epidural injection of lidocaine, tramadol, and lidocaine-tramadol for epidural anesthesia in cattle. J Vet Pharmacol Ther. 2010;33:439-43 pubmed publisher
    ..The aim of this study is to directly compare the time of onset and duration of analgesia produced by a tramadol and lidocaine-tramadol combination with that produced by lidocaine administration in the epidural space of Cattle...
  32. Kaynar M, Kilic O, Yurdakul T. On-demand tramadol hydrochloride use in premature ejaculation treatment. Urology. 2012;79:145-9 pubmed publisher
    To determine the efficacy of tramadol in premature ejaculation (PE) treatment compared with placebo.
  33. Thorn D, Zhang Y, Peng B, Winter J, Li J. Effects of imidazoline I? receptor ligands on morphine- and tramadol-induced antinociception in rats. Eur J Pharmacol. 2011;670:435-40 pubmed publisher
    ..This study examined the antinociceptive effects of the opioids morphine (0.1-10 mg/kg) and tramadol (3...
  34. Hugunin K, Fry C, Shuster K, Nemzek J. Effects of tramadol and buprenorphine on select immunologic factors in a cecal ligation and puncture model. Shock. 2010;34:250-60 pubmed
    ..Female ICR mice were divided into four treatment groups (Ringer's lactate solution, high- or low-dose tramadol,buprenorphine) for 3-week mortality studies (n = 12 per treatment)...
  35. Takasuga S, Yamamoto R, Mafune S, Sutoh C, Kominami K, Yoshida Y, et al. In-vitro and in-vivo transdermal iontophoretic delivery of tramadol, a centrally acting analgesic. J Pharm Pharmacol. 2011;63:1437-45 pubmed publisher
    The feasibility of transdermal delivery of tramadol, a centrally acting analgesic, by anodal iontophoresis using Ag/AgCl electrodes was investigated in vitro and in vivo.
  36. Taghaddosinejad F, Mehrpour O, Afshari R, Seghatoleslami A, Abdollahi M, Dart R. Factors related to seizure in tramadol poisoning and its blood concentration. J Med Toxicol. 2011;7:183-8 pubmed publisher
    This study examines the relation between seizure and plasma tramadol concentration in patients with tramadol poisoning, as a novel centrally acting analgesic used for the treatment of mild to severe pain...
  37. Guedes A, Matthews N, Hood D. Effect of ketamine hydrochloride on the analgesic effects of tramadol hydrochloride in horses with signs of chronic laminitis-associated pain. Am J Vet Res. 2012;73:610-9 pubmed publisher
    To investigate the effects of ketamine hydrochloride on the analgesic effects of tramadol hydrochloride in horses with signs of pain associated with naturally occurring chronic laminitis.
  38. Yang C, Li W, Yu H, Gao Z, Liu X, Zhou Z, et al. Tramadol pretreatment enhances ketamine-induced antidepressant effects and increases mammalian target of rapamycin in rat hippocampus and prefrontal cortex. J Biomed Biotechnol. 2012;2012:175619 pubmed publisher
    ..Moreover, tramadol also has potential antidepressant effects...
  39. Alvarez P, Brun A, Labertrandie A, Lopez J, Correa A, Constandil L, et al. Antihyperalgesic effects of clomipramine and tramadol in a model of posttraumatic trigeminal neuropathic pain in mice. J Orofac Pain. 2011;25:354-63 pubmed
    ..pain such as spontaneous pain, cold allodynia, and chemical÷inflammatory hyperalgesia, and to use this model to investigate the antinociceptive effects of clomipramine and tramadol, two drugs used for the treatment of neuropathic pain.
  40. Matouskova O, Slanar O, Chytil L, Perlik F. Pupillometry in healthy volunteers as a biomarker of tramadol efficacy. J Clin Pharm Ther. 2011;36:513-7 pubmed publisher
    The opioid effect of tramadol, which can be detected by pupillary response, is predominantly mediated by the O-demethylated metabolite, formed via CYP2D6...
  41. Tekelioglu U, Apuhan T, Akkaya A, Demirhan A, Yildiz I, Simşek T, et al. Comparison of topical tramadol and ketamine in pain treatment after tonsillectomy. Paediatr Anaesth. 2013;23:496-501 pubmed publisher
    The primary objective of this study is to evaluate the effects of topically applied ketamine or tramadol on early postoperative pain scores in children undergoing tonsillectomy...
  42. KuKanich B, Papich M. Pharmacokinetics and antinociceptive effects of oral tramadol hydrochloride administration in Greyhounds. Am J Vet Res. 2011;72:256-62 pubmed publisher
    To determine the pharmacokinetics of tramadol, the active metabolite O-desmethyltrcamadol, and the metabolites N-desmethyltramadol and N,O-didesmethyltramadol after oral tramadol administration and to determine the antinociceptive effects ..
  43. Farajidana H, Hassanian Moghaddam H, Zamani N, Sanaei Zadeh H. Tramadol-induced seizures and trauma. Eur Rev Med Pharmacol Sci. 2012;16 Suppl 1:34-7 pubmed
    To determine the prevalence, type and site of the injuries due to tramadol-induced seizures in the patients who had referred after its overdose or use of its therapeutic dose.
  44. Sarsu S, Mizrak A, Karakurum G. Tramadol use for axillary brachial plexus blockade. J Surg Res. 2011;165:e23-7 pubmed publisher
    We investigated the effects of tramadol added to the mixture of local anesthetic for axillary brachial plexus blockade (ABB) in patients to have undergone hand and forearm surgery.
  45. Zegre Cannon C, Kissling G, Goulding D, King Herbert A, Blankenship Paris T. Analgesic effects of tramadol, carprofen or multimodal analgesia in rats undergoing ventral laparotomy. Lab Anim (NY). 2011;40:85-93 pubmed publisher
    In this study, the authors evaluated the analgesic efficacy of tramadol (an opioid-like analgesic), carprofen (a nonsteroidal anti-inflammatory drug) and a combination of both drugs (multimodal therapy) in a rat laparotomy model...
  46. Taheri R, Shayeghi S, Razavi S, Sadeghi A, Ghabili K, Ghojazadeh M, et al. Efficacy of bupivacaine-neostigmine and bupivacaine-tramadol in caudal block in pediatric inguinal herniorrhaphy. Paediatr Anaesth. 2010;20:866-72 pubmed publisher
    ..Therefore, the purpose of this study was to evaluate the effectiveness and safety of bupivacaine in combination with either neostigmine or tramadol for caudal block in children undergoing inguinal herniorrhaphy.
  47. Ayatollahi V, Behdad S, Hatami M, Moshtaghiun H, Baghianimoghadam B. Comparison of peritonsillar infiltration effects of ketamine and tramadol on post tonsillectomy pain: a double-blinded randomized placebo-controlled clinical trial. Croat Med J. 2012;53:155-61 pubmed
    To assess the effect of peritonsillar infiltration of ketamine and tramadol on post tonsillectomy pain and compare the side effects.
  48. Baker B, Sladky K, Johnson S. Evaluation of the analgesic effects of oral and subcutaneous tramadol administration in red-eared slider turtles. J Am Vet Med Assoc. 2011;238:220-7 pubmed publisher
    To determine the dose- and time-dependent changes in analgesia and respiration caused by tramadol administration in red-eared slider turtles (Trachemys scripta).
  49. Salman S, Sy S, Ilett K, Page Sharp M, Paech M. Population pharmacokinetic modeling of tramadol and its O-desmethyl metabolite in plasma and breast milk. Eur J Clin Pharmacol. 2011;67:899-908 pubmed publisher
  50. Esme H, Kesli R, Apiliogullari B, Duran F, Yoldas B. Effects of flurbiprofen on CRP, TNF-?, IL-6, and postoperative pain of thoracotomy. Int J Med Sci. 2011;8:216-21 pubmed
  51. Kongara K, Chambers J, Johnson C. Effects of tramadol, morphine or their combination in dogs undergoing ovariohysterectomy on peri-operative electroencephalographic responses and post-operative pain. N Z Vet J. 2012;60:129-35 pubmed publisher
    ..electroencephalogram (EEG) responses and post-operative analgesic efficacy of pre-operative morphine or tramadol with a combination of low-dose pre-operative morphine and post-operative tramadol, in dogs undergoing ..
  52. Díaz Reval M, Carrillo Munguía N, Martínez Casas M, González Trujano M. Tramadol and caffeine produce synergistic interactions on antinociception measured in a formalin model. Pharmacol Biochem Behav. 2010;97:357-62 pubmed publisher
    ..The aim of this study was to determine the antinociceptive effect of tramadol and caffeine administered separately or in combination, as well as their synergistic interaction...
  53. Nossaman V, Ramadhyani U, Kadowitz P, Nossaman B. Advances in perioperative pain management: use of medications with dual analgesic mechanisms, tramadol & tapentadol. Anesthesiol Clin. 2010;28:647-66 pubmed publisher
    ..b>Tramadol and tapentadol hydrochloride are novel in that their analgesic actions occur at multiple sites...