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

Abstract

Objective

This paper presents and discusses recent evidence on the pathophysiological mechanisms of pain. The role of tapentadol – an opioid characterized by an innovative mechanism of action (i.e. µ-opioid receptor [MOR] agonism and inhibition of noradrenaline [NA] reuptake [NRI]) – in the modulation of pain, and the most recent pharmacological evidence on this molecule (e.g. the µ-load concept) are also presented and commented upon.

Methods

Narrative review.

Results

Solid evidence has highlighted the importance of central sensitization in the transition from acute to chronic pain. In particular, the noradrenergic system holds a major role in limiting central sensitization and the progression to chronic pain. Therefore, pharmacological modulation of the noradrenergic system appears to be a well-grounded strategy for the control of chronic pain. Tapentadol is characterized by a to-date-unique mechanism of action, since it acts both as a MOR agonist and as an inhibitor of NA reuptake. The synergistic interaction of these two mechanisms allows a strong analgesic effect by acting on both ascending and descending pathways. Of note, the reduced µ-load of tapentadol limits the risk of opioid-related adverse events, such as gastrointestinal disturbances. Moreover, the NA component becomes predominant, at least, in some types of pain, with consequent specific clinical efficacy in the treatment of neuropathic and chronic pain.

Conclusions

According to these characteristics, tapentadol appears suitable in the treatment of severe uncontrolled chronic pain characterized by both a nociceptive and a neuropathic component, such as osteoarthritis or back pain.

Keywords:

• Tapentadol
• neuropathic pain
• pharmacology
• µ-load
• chronic pain
• central sensitization
• noradrenaline
• opioids
• μ-receptor

Transparency

Declaration of funding

The article was initiated by Grünenthal Italia Srl, who also supported the medical writing and editorial costs.

Declaration of financial/other relationships

AHD has received speaker fees from Grunenthal, Teva, and Allergan. FCaraci has received speaker fees from Grunenthal, Lundbeck, and Janssen. FColuzzi served as a speaker for Grunenthal, Angelini, and Malesci. PR has received speaker fees from Grunenthal, Angelini, and Molteni. FM has received speaker fees from Grunenthal, MSD, Molteni, and Kyowa Kirin. SM has received speaker fees from Grunenthal, Molteni, Angelini, and Kyowa Kirin. GR has received speaker fees from Grunenthal. FN is an employee of Grunenthal. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work but have no other relevant financial relationships to disclose.

Author contributions

All authors contributed to the definition of the scopes of this manuscript and the collection of data. AHD wrote the first draft, which was revised by all other authors. All authors have read and approved the final draft.

Acknowledgements

Editorial assistance was provided by Luca Giacomelli, PhD, whose assistance was supported by Grunenthal, and Aashni Shah and Sara Di Nunzio (Polistudium srl, Milan, Italy), whose assistance was supported by internal funds.