Neuroimmune interactions are known to play a key role in maintaining peripheral tissue homeostasis, particularly in models of allergy and infection. However, their contribution to tissue repair remains incompletely understood. Previous studies have shown that autonomic nerves—especially sympathetic nerves—facilitate skin healing by modulating the activity of keratinocytes, immune cells, and endothelial cells. By contrast, it is still unclear whether sensory neurons, which detect tissue injury and generate perceptions such as pain and heat, also play a pivotal role in tissue repair.

Emerging evidence indicates that nociceptors, the primary mediators of pain sensation, can promote repair in adipose tissue, skin, muscle, and cornea through diverse mechanisms, including immunoregulation. These mechanisms may include regulation of immune cell recruitment and polarization, modulation of vascular tone and permeability, effects on fibroblasts and extracellular matrix dynamics, and control of epithelial proliferation and differentiation. Axon reflexes and neuropeptides such as CGRP and substance P can drive local neurogenic inflammation and vasodilation, while interactions with trophic factors (e.g., NGF, BDNF, and GDNF-family signaling) may influence progenitor cells and regeneration.

In this Research Topic, we will discuss how sensory neurons regulate tissue repair and regeneration across different tissues and consider their translational potential in clinical settings, focusing (but not limited) to the following subtopics:

1. Sensory neuron diversity and tissue-specific regeneration (e.g., skin, cornea, muscle, bone, heart)

2. Mechanisms of sensory neuron–driven repair (e.g., neuropeptides, immune regulation, angiogenesis, pain signaling)

3. Pathological consequences of sensory neuron dysfunction (neuropathy, non-healing wounds, fibrosis)

4: Therapeutic, bioengineering, and neuromodulatory strategies, such as acupuncture, to restore or modulate sensory neuron function.

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Sensory neurons: drivers of tissue repair and regeneration