articleBone ResearchJan 19, 2026GOLD OA

Neutrophil-initiated nociceptive ingrowth orchestrates inflammation resolution to potentiate bone regeneration

Shanghai Jiao Tong University · National Clinical Research Center for Digestive Diseases · +10 more institutions

PubMed
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Abstract

Abstract Nociceptive pain is a cardinal feature of traumatic and inflammatory bone diseases. However, whether and how nociceptors actively regulate the immune response during bone regeneration remains unclear. Here, we found that neutrophil-triggered nociceptive ingrowth functioned as negative feedback regulation to inflammation during bone healing. A unique Il4ra + Ccl2 high neutrophil subset drove intense postinjury TRPV1 + nociceptive ingrowth, which in return dissipated inflammation by activating the production of pro-resolving mediator lipoxin A4 (LXA4) in osteoblasts. Mechanistically, osteoblastic autophagy activated by nociceptor-derived calcitonin gene-related peptide (CGRP) suppressed the nuclear…

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