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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01024

Rescue of noradrenergic system as a novel pharmacological strategy in the treatment of chronic pain: focus on microglia activation

  • 1Department of Drug Sciences, University of Catania, Italy
  • 2Oasi Maria SS. Association ONLUS (IRCCS), Italy
  • 3Department of Biomedical and Biotechnological Sciences, University of Catania, Italy

Different types of pain can evolve towards a chronic condition characterized by hyperalgesia and allodynia, with an abnormal response to normal or even innocuous stimuli, respectively.
A key role in endogenous analgesia is recognized to descending noradrenergic pathways that originate from the locus coeruleus and project to the dorsal horn of the spinal cord. Impairment of this system is associated with pain chronicization. More recently, activation of glial cells, in particular microglia, towards a pro-inflammatory state has also been implicated in the transition from acute to chronic pain. Both α2- and β2-adrenergic receptors are expressed in microglia and their activation leads to acquisition of an anti-inflammatory phenotype. This review analyses in more detail the interconnection between descending noradrenergic system and neuroinflammation, focusing on drugs that, by rescuing the noradrenergic control, exert also an anti-inflammatory effect, ultimately leading to analgesic effect. More specifically the potential efficacy in the treatment of neuropathic pain of classes of drugs will be analyzed. On one side drugs acting as inhibitors of the reuptake of serotonin and noradrenaline, such as duloxetine and venlafaxine, on the other, tapentadol, inhibitor of the reuptake of noradrenalin and agonist of the µ-opioid receptor.

Keywords: neuropathic pain, Neuroinflammantion, Microglia, Noradrenalin reuptake inhibitors, Opioid receptor agonists

Received: 13 Jul 2019; Accepted: 12 Aug 2019.

Copyright: © 2019 Caraci, Merlo, Drago, Caruso, Parenti and Sortino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Filippo Caraci, Department of Drug Sciences, University of Catania, Catania, Italy,