Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain.

Lidia Bravo,Esther Berrocoso,Juan Antonio Micó,Meritxell Llorca-Torralba

doi:10.3389/fnins.2019.01268

Abstract

Monoamines are involved in regulating the endogenous pain system and indeed, peripheral and central monoaminergic dysfunction has been demonstrated in certain types of pain, particularly in neuropathic pain. Accordingly, drugs that modulate the monaminergic system and that were originally designed to treat depression are now considered to be first line treatments for certain types of neuropathic pain (e.g., serotonin and noradrenaline (and also dopamine) reuptake inhibitors). The analgesia induced by these drugs seems to be mediated by inhibiting the reuptake of these monoamines, thereby reinforcing the descending inhibitory pain pathways. Hence, it is of particular interest to study the monoaminergic mechanisms involved in the development and maintenance of chronic pain. Other analgesic drugs may also be used in combination with monoamines to facilitate descending pain inhibition (e.g., gabapentinoids and opioids) and such combinations are often also used to alleviate certain types of chronic pain. By contrast, while NSAIDs are thought to influence the monoaminergic system, they just produce consistent analgesia in inflammatory pain. Thus, in this review we will provide preclinical and clinical evidence of the role of monoamines in the modulation of chronic pain, reviewing how this system is implicated in the analgesic mechanism of action of antidepressants, gabapentinoids, atypical opioids, NSAIDs and histaminergic drugs.

Highlights

The monoaminergic system is implicated in the maintenance of homeostasis in the nervous system and among their distinct functions, monoamines regulate the endogenous pain system (Bannister et al, 2009)
Monoamines as Target in Chronic Pain these drugs have helped clarify the mechanism of action of some so-called atypical analgesics, the primary effects of which do not involve the monoaminergic system even though their global efficacy as analgesics might well be driven by monoamines
We will present information from various preclinical and clinical studies that investigated the role of monoamines in chronic pain, as well as studies that assessed the mechanisms of action of actual and potential analgesics to treat different types of chronic pain

Summary

INTRODUCTION

The monoaminergic system is implicated in the maintenance of homeostasis in the nervous system and among their distinct functions, monoamines regulate the endogenous pain system (Bannister et al, 2009). Peripheral α-adrenergic stimulation does not affect pain sensation in healthy conditions but interestingly, such excitation enhances pain sensation in chronic pain (Shea and Perl, 1985) This pro-nociceptive effect is the result of increased excitability of primary sensory neurons, known as hypersensitivity to innocuous and noxious stimuli. The increase in α2A-AR efficiency could explain why antidepressants induce spinal analgesia in chronic pain conditions (Luo et al, 1994; Malmberg et al, 2001; Bantel et al, 2005) These central adaptive changes suggest that after nerve injury, the descending noradrenergic inhibitory tone may be FIGURE 1 | Peripheral and central adaptive changes observed in animal models of chronic pain. In animal models of neuropathic pain, the antagonism of 5-HT1A receptors induces analgesia or TABLE 1 | Monoaminergic dysfunction in preclinical models of pain

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Findings

DISCUSSION