**Shedding Light on the Pharmacological Interactions between** µ**-Opioid Analgesics and Angiotensin Receptor Modulators: A New Option for Treating Chronic Pain**

**Kornél Király 1,\* ,†, Dávid Á. Karádi 1,†, Ferenc Zádor 1,2, Amir Mohammadzadeh <sup>1</sup> , Anna Rita Galambos <sup>1</sup> , Mihály Balogh <sup>1</sup> , Pál Riba <sup>1</sup> , Tamás Tábi <sup>2</sup> , Zoltán S. Zádori <sup>1</sup> , Éva Szök˝o <sup>2</sup> , Susanna Fürst <sup>1</sup> and Mahmoud Al-Khrasani 1,\***


**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.

**Keywords:** µ-opioid analgesics; angiotensin receptors; chronic pain; neuropathic pain
