Crosstalk between Mu-Opioid receptors and neuroinflammation: Consequences for drug addiction and pain

• Published in: Neuroscience and biobehavioral reviews Vol. 145; p. 105011
• Main Authors: Cuitavi, Javier, Torres-Pérez, Jose Vicente, Lorente, Jesús David, Campos-Jurado, Yolanda, Andrés-Herrera, Paula, Polache, Ana, Agustín-Pavón, Carmen, Hipólito, Lucía
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01-02-2023
• Subjects: Analgesics, Opioid - pharmacology; Analgesics, Opioid - therapeutic use; Humans; Morphine - therapeutic use; Neuroimmunity; Neuroinflammatory Diseases; Nociception; Opioid signaling; Pain - drug therapy; Receptors, Opioid, mu - metabolism; Reinforcement; Substance-Related Disorders - drug therapy; VTA; DAMGO; JNK; NF-kB; IKKs; CNS; mRNA; PFC; LPS; NAc; GRK2; SNPs; Reinforcement; Nociception; IL; DOR; MORs; Neuroimmunity; PKC; i.p; siRNA; Akt; MAPK; ORL1; KOR; OIH; ORs; MEK; TNF-α; ROS; NKR1; Opioid signaling; MCLS; TLRs; CFA; ERK
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2022.105011

Mu-Opioid Receptors (MORs) are well-known for participating in analgesia, sedation, drug addiction, and other physiological functions. Although MORs have been related to neuroinflammation their biological mechanism remains unclear. It is suggested that MORs work alongside Toll-Like Receptors to enhance the release of pro-inflammatory mediators and cytokines during pathological conditions. Some cytokines, including TNF-α, IL-1β and IL-6, have been postulated to regulate MORs levels by both avoiding MOR recycling and enhancing its production. In addition, Neurokinin‐1 Receptor, also affected during neuroinflammation, could be regulating MOR trafficking. Therefore, inflammation in the central nervous system seems to be associated with altered/increased MORs expression, which might regulate harmful processes, such as drug addiction and pain. Here, we provide a critical evaluation on MORs’ role during neuroinflammation and its implication for these conditions. Understanding MORs’ functioning, their regulation and implications on drug addiction and pain may help elucidate their potential therapeutic use against these pathological conditions and associated disorders.
•Mu-Opioid receptors (MORs) are drivers of neuroinflammation when activated.•Cytokines regulate MORs expression and probably trafficking.•The MORs-neuroinflammation crosstalk conditions relapse and addictive behaviors.•Alterations in cytokines production and Mu-Opioid receptors modulate pain.