<p>Pharmacological rationale for tapentadol therapy: a review of new evidence</p>

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.

Modulation of sensitization processes in the management of pain and the importance of descending pathways: a role for tapentadol?

“…Multiple regions are involved, such as the hypothalamus, amygdala and cortex, as well as the nucleus accumbens and the periaqueductal grey [5,8]. Pathways run back from the brain to the spinal cord and many of the descending tracts are monoaminergic: at spinal synapses, the A c c e p t e d M a n u s c r i p t descending pathways induce the release of several mediators, including endogenous opioids, NA, serotonin (5-HT) and gamma-aminobutyric acid (GABA), thus modulating the transmission between primary and secondary neurons [9]. Remarkably, NA pathways exert an inhibitory effect on the transmission of acute and chronic pain, thus counteracting the establishment of chronic pain [9].…”

“…Pathways run back from the brain to the spinal cord and many of the descending tracts are monoaminergic: at spinal synapses, the A c c e p t e d M a n u s c r i p t descending pathways induce the release of several mediators, including endogenous opioids, NA, serotonin (5-HT) and gamma-aminobutyric acid (GABA), thus modulating the transmission between primary and secondary neurons [9]. Remarkably, NA pathways exert an inhibitory effect on the transmission of acute and chronic pain, thus counteracting the establishment of chronic pain [9]. Conversely, serotoninergic pathways may have a facilitatory effect in the advanced stages of chronicity and therefore, might play a pro-nociceptive role [10].…”

“…Conversely, serotoninergic pathways may have a facilitatory effect in the advanced stages of chronicity and therefore, might play a pro-nociceptive role [10]. Imbalance between amplified spinal ascending signals and inadequate activation of the descending inhibitory pathways plays a key role in the development and maintenance of many chronic pain syndromes [9]. Activity in the descending noradrenergic system can be gauged in animals and humans by diffuse noxious inhibitory controls (DNIC) and conditioned pain modulation (CPM), respectively, whereby one painful stimulus can inhibit another [11].…”

“…Effective involvement of inhibitory descending pathways could protect against the development of chronic pain [27]. Moreover, the activation of the opioid receptor is particularly relevant in acute nociceptive pain, while the inhibition of NA reuptake activity plays a crucial role in chronic neuropathic pain [9].…”

“…Tapentadol is a centrally acting analgesic drug, considered the first representative of the MOR-NRI class of drugs. It displays an analgesic efficacy comparable to that of strong classical opioids [9,37,38]. The pharmacology of tapentadol has recently been reviewed [9].…”