Mas-related G-protein-coupled receptors constitute a distinct family of GPCRs expressed in some subsets of sensory neurons and immune cells. Increasing evidence highlights their contribution to the modulation of nociceptive signaling and neuroimmune interactions. Recent studies demonstrate that Mas-related G-protein-coupled receptors are implicated not only in itch transmission but also in the pathophysiology of neuropathic pain, where aberrant receptor activity influences neuronal excitability, glial activation, and inflammatory responses. This review summarizes current knowledge on the molecular mechanisms by which Mas-related G-protein-coupled receptors regulate pain hypersensitivity, including their interactions with ion channels, neuropeptides, and immune mediators. Moreover, the potential of targeting specific Mas-related G-protein-coupled receptor subtypes for therapeutic intervention is discussed, emphasizing their promise as novel druggable candidates for neuropathic pain, the emerging management. Clarifying the roles of Mas-related G-protein-coupled receptors in sensory modulation may provide critical insights into the development of mechanism-based analgesics.
Mario García-Domínguez (Thu,) studied this question.