Tapentadol in the management of chronic low back pain: a novel approach to a complex condition?

Joseph Pergolizzi1, Eli Alon2, Ralf Baron3, Cesare Bonezzi4, Jan Dobrogowski5, Rafael Gálvez6, Troels Jensen7, Hans-Georg Kress8, Marco AE Marcus9, Bart Morlion10, Serge Perrot11, Rolf-Detlef Treede121Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Universitätsspital Zurich, Switzerland; 3Universitätsklinikum Schleswig-Holstein, Kiel, Germany; 4Fondazione Salvatore Maugeri, Pavia, Italy; 5Zaklad Badania i Leczenia Bólu, Kraków, Poland; 6Hospital Universitario Virgen de las Nieves, Granada, Spain; 7Aarhus University, Denmark; 8Medical University of Vienna, Austria; 9Maastricht University Medical Center and University of Muenster, Maastricht, The Netherlands; 10University Hospitals Leuven, Belgium; 11Hôpital Dieu, Paris, France; 12Ruprecht-Karls-University, Heidelberg, GermanyAbstract: Chronic pain affects approximately 1 in 5 people in Europe, and around half of sufferers receive inadequate pain management. The most common location is the lower back. Pharmacological treatment of this condition is challenging because of the range of causative mechanisms and the difficulty of balancing analgesic efficacy and tolerability. An international panel of clinical pain specialists met in September, 2009, to discuss the treatment of chronic low back pain, and to review preclinical and clinical data relating to the new analgesic, tapentadol. A lack of consensus exists on the best treatment for low back pain. The range of regularly prescribed pharmacological agents extends from nonopioids (paracetamol, NSAIDs, and COX-2 inhibitors) to opioids, antidepressants and anticonvulsants. Pain relief may be compromised, however, by an undetected neuropathic component or intolerable side effects. Treatment is potentially life-long and effective analgesics are urgently needed, with demonstrable long-term safety. Combining separate agents with different mechanisms of action could overcome the limitations of present pharmacological therapy, but clinical evidence for this approach is currently lacking. Tapentadol combines µ-opioid agonism with noradrenaline reuptake inhibition in a single molecule. There is strong evidence of synergistic antinociception between these two mechanisms of action. In preclinical and clinical testing, tapentadol has shown efficacy against both nociceptive and neuropathic pain. Preclinical data indicate that tapentadol’s µ-opioid agonism makes a greater contribution to analgesia in acute pain, while noradrenaline reuptake inhibition makes a greater contribution in chronic neuropathic pain models. Tapentadol also produces fewer adverse events than oxycodone at equianalgesic doses, and thus may have a ‘µ-sparing effect’. Current evidence indicates that tapentadol’s efficacy/tolerability ratio may be better than those of classical opioids. However, further research is needed to establish its role in pain management.Keywords: chronic low back pain, neurophysiological changes, neuropathic component, multimechanistic approach, efficacy/side effect ratio, tapentadol