Opioids are the most effective analgesics used in the clinical management of cancer pain or non-cancer pain. However, chronic opioids therapy can cause many side effects including respiratory depression, nausea, sedation, itch, constipation, analgesic tolerance, hyperalgesia, high addictive potential, and abuse liability. Opioids exert their effects through binding to the opioid receptors belonging to the G-protein coupled receptors (GPCRs) family, including mu opioid receptor (MOR), delta opioid receptor (DOR), and kappa opioid receptor (KOR). Among them, MOR is essential for opioid-induced analgesia and also responsible for adverse effects of opioids. Importantly, MOR can form heterodimers with other opioid receptors and non-opioid receptors in vitro and in vivo, and has distinct pharmacological properties, different binding affinities for ligands, downstream signaling, and receptor trafficking. This mini review summarized recent progress on the function of Mu opioid receptor heterodimers, and we proposed that targeting mu opioid receptor heterodimers may represent an opportunity to develop new therapeutics, especially for chronic pain treatment.

Macrophages are present in many mechanically active tissues and are often subjected to varying degrees of mechanical stimulation. Macrophages play a crucial role in resisting pathogen invasion and maintaining tissue homeostasis. Piezo-type mechanosensitive channel component 1 (Piezo1) is the main cation channel involved in the rapid response to mechanical stimuli in mammals. This channel plays a crucial role in controlling blood pressure and motor performance and regulates urinary osmotic pressure and epithelial cell proliferation and division. In recent years, numerous studies have shown that in macrophages, Piezo1 not only plays a role in regulating the aforementioned physiological processes but also participates in multiple pathological processes such as inflammation and cancer. In this review, we summarize the research progress on Piezo1-mediated regulation of macrophage-mediated inflammatory responses through downstream signalling pathways and the aerobic glycolysis pathway.

Intracerebral hemorrhage (ICH) is the most common subtype of hemorrhagic stroke causing significant morbidity and mortality. Previously clinical treatments for ICH have largely been based on a single pathophysiological perspective, and there remains a lack of curative interventions. Following the rupture of cerebral blood vessels, blood metabolites activate resident immune cells such as microglia and astrocytes, and infiltrate peripheral immune cells, leading to the release of a series of inflammatory mediators. Degradation of hemoglobin produces large amounts of iron ions, leading to an imbalance of iron homeostasis and the production of large quantities of harmful hydroxyl radicals. Neuroinflammation and dysregulation of brain iron metabolism are both important pathophysiological changes in ICH, and both can exacerbate secondary brain injury. There is an inseparable relationship between brain iron metabolism disorder and activated glial cells after ICH. Glial cells participate in brain iron metabolism through various mechanisms; meanwhile, iron accumulation exacerbates neuroinflammation by activating inflammatory signaling pathways modulating the functions of inflammatory cells, and so on. This review aims to explore neuroinflammation from the perspective of iron metabolism, linking the complex pathophysiological changes, delving into the exploration of treatment approaches for ICH, and offering insights that could enhance clinical management strategies.