Pharmacological rationale for tapentadol therapy: a review of new evidence

Patrizia Romualdi,1 Mariagrazia Grilli,2 Pier Luigi Canonico,3 Massimo Collino,4 Anthony H Dickenson5 1Department of Pharmacy and Biotechnologies Alma Mater Studiorum, University of Bologna, Bologna 40126, Italy; 2Laboratory of Neuroplasticity, Department Pharmaceutical Sciences, University of Piemonte Orientale, Novara 28100, Italy; 3Departiment of Pharmacological Sciences, University of Piemonte Orientale, Novara 28100, Italy; 4Department of Drug Science and Technology, University of Turin, Turin 10121, Italy; 5Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK Abstract: Chronic pain could be considered as a neurological disorder. Therefore, appropriate selection of the therapy, which should consider the pathophysiological mechanisms of pain, can result in a successful analgesic outcome. Tapentadol is an analgesic drug which acts both as a μ-opioid receptor (MOR) agonist and as a noradrenaline reuptake inhibitor (NRI), thereby generating a synergistic action in terms of analgesic efficacy, but not for the burden of adverse effects. Therefore, tapentadol can be defined as the first “MOR-NRI” drug. This molecule holds the potential to address at least some of the current limitations of analgesic therapy due to its unique mechanism of action and has shown to be safe and effective in the treatment of chronic pain of cancer and noncancer etiologies including nociceptive, neuropathic and mixed pain. In particular, the MOR component of tapentadol activity predominantly allows for analgesia in nociceptive pain; on the other hand, the NRI component contributes, now in a predominant manner, for analgesic efficacy in cases of neuropathic pain states. This paper will discuss recent pieces of evidence on the pathophysiology of pain, the background on tapentadol and then present some new studies on how the unique mechanism of action of tapentadol provides a key role in its analgesic efficacy in a number of pain states and with a favorable safety profile. Keywords: tapentadol, neuropathic pain, pain chronicization