Abstract

The current protocols for neuropathic pain management include µ-opioid receptor (MOR) analgesics alongside other drugs; however, there is debate on the effectiveness of opioids. Nevertheless, dose escalation is required to maintain their analgesia, which, in turn, contributes to a further increase in opioid side effects. Finding novel approaches to effectively control chronic pain, particularly neuropathic pain, is a great challenge clinically. Literature data related to pain transmission reveal that angiotensin and its receptors (the AT1R, AT2R, and MAS receptors) could affect the nociception both in the periphery and CNS. The MOR and angiotensin receptors or drugs interacting with these receptors have been independently investigated in relation to analgesia. However, the interaction between the MOR and angiotensin receptors has not been excessively studied in chronic pain, particularly neuropathy. This review aims to shed light on existing literature information in relation to the analgesic action of AT1R and AT2R or MASR ligands in neuropathic pain conditions. Finally, based on literature data, we can hypothesize that combining MOR agonists with AT1R or AT2R antagonists might improve analgesia.

Highlights

  • Among different types of chronic pain, neuropathic pain is defined by the International Association for the Study of Pain (IASP) as pain caused by a lesion or disease of the somatosensory nervous system (IASP 2012)

  • Current evidence indicates that AT1, AT2, and MASRs are involved in the control of neuropathic pain; their mechanism of action related to neuropathic pain has not yet been fully verified

  • Data on the impact of AT2R in neuropathic pain are contradictory, though its activation or inhibition can result in neuroprotection or analgesia, respectively; future studies are needed to justify this issue

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Summary

Introduction

Among different types of chronic pain, neuropathic pain is defined by the International Association for the Study of Pain (IASP) as pain caused by a lesion or disease of the somatosensory nervous system (IASP 2012). Continuing preclinical research based on the application of multi-target drugs or combination strategies that involve implementing different agents might bring a new treatment option for neuropathic pain. In the former case, for instance, applying opioid receptor ligands that display agonist and non-opioid effects, such as tapentadol, display both the MOR agonist and norepinephrine reuptake inhibitory effects in the same molecule [15]. We need to consider how the individual drugs affect pain transmission

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