The Neuroimmune Circuitry of Peripheral Sensory Neuron Subtypes in Chronic Pain

Peripheral sensory neurons, long appreciated for their role in detecting environmental stimuli, also play an active role in local and systemic immune responses. In response to tissue damage, the coordinated activation of peripheral sensory neurons and immune cells facilitates tissue repair. When dysregulated, however, these neuroimmune interactions can become maladaptive and contribute to chronic disorders such as chronic pain or headache. Recent single-cell transcriptomic studies have uncovered multiple distinct sensory neuron subtypes, each with unique molecular profiles, anatomical niches, and immune functions. In this review, we examine how distinct sensory neuron subtypes coordinate immune responses in barrier and internal tissues, forming cell type- and context-specific neuroimmune circuits. We also discuss how disruption of these circuits contributes to neuroinflammatory diseases such as atopic dermatitis and neuropathic pain. Clarifying these subtype-specific neuroimmune mechanisms offers a path toward more precise and effective therapies that target maladaptive neuroimmune circuitry in multiple disorders.