Brain Allergy: Molecular Mechanisms with Neuro-Immune Interactions in Light of Therapeutic Innovation

Abstract

The present review study aims to systematically analyze current knowledge on neuro-immune mechanisms across allergic diseases, evaluate emerging therapeutic strategies targeting these pathways (including neuropeptide antagonists and TRP channel modulators), and identify critical gaps for future research to enable development of novel, dual-targeting treatments that address both neural and immunological components of allergy pathogenesis. Allergic diseases such as asthma, atopic dermatitis, and allergic rhinitis are increasingly understood as disorders of dysregulated neuro-immune crosstalk, where bidirectional interactions between sensory neurons and immune cells amplify inflammation through neuropeptides (substance P, CGRP), neurotrophies (NGF, BDNF), and autonomic signaling. The bidirectional relationship between stress pathways and allergic inflammation involves complex neuroendocrine-immune interactions. The behavioural and cognitive aspects of allergy demonstrate the profound integration between psychological processes and immune function. The remarkable capacity of the nervous system to modulate immune responses through learned associations is exemplified by classical conditioning experiments in allergic disorders. This review study synthesizes mechanisms like mast cell-neuron feedback loops, stress-induced glucocorticoid resistance, and disease-specific pathways (e.g., IL-31/TRPV1+ in itch, vagal-plasma cell circuits in asthma), while highlighting behavioural influences (Pavlovian conditioning, stress) and emerging therapies targeting neuro-immune axes (NK1R antagonists, TRP modulators). Therapeutically, novel approaches targeting neuro-immune interfaces show promise, including NK1 receptor antagonists, TRP channel modulators, and neurotrophic inhibitors, though challenges remain in achieving tissue specificity and preserving physiological neural functions. This knowledge opens new therapeutic possibilities that extend beyond conventional immunosuppression. Challenges in developing tissue-specific interventions and the need for integrated, biomarker-driven approaches are discussed, offering a roadmap for next-generation allergy treatments that address both neural and immunological dysfunction.