Acupuncture accelerated skin wound healing in mice by activating the CGRP neuropeptide pathway, which reprogrammed inflammatory macrophages into healing-promoting ones.
CGRP pathway = key mediatorBlocking the CGRP receptor with BIBN4096 abolished acupuncture's wound healing and macrophage reprogramming effects — proving the neuropeptide pathway is essential
What the researchers found
Daily acupuncture around full-thickness skin wounds in mice significantly improved wound closure, collagen deposition, and tissue repair quality over 10 days. The treatment enhanced M2 macrophage polarization (the healing-promoting type) within wounds, reduced systemic macrophage burden in the spleen, and lowered both local and systemic levels of the inflammatory cytokines IL-1β and IL-6.
The mechanism was identified as the CGRP-RAMP1-TSP-1 signaling pathway. Blocking this pathway with the CGRP receptor antagonist BIBN4096 abolished acupuncture's effects on macrophage reprogramming and wound healing. However, the anti-inflammatory cytokine suppression was only partially CGRP-dependent, indicating that acupuncture also works through additional neuropeptide or neuronal pathways that remain to be identified.
Why it matters
CGRP is one of the most abundant neuropeptides in the body, and this study provides mechanistic evidence for how nerve-derived peptide signaling can drive immune cell reprogramming to accelerate wound healing. Beyond explaining acupuncture's effects, these findings highlight CGRP as a potential therapeutic target for improving wound healing in patients with chronic or non-healing wounds.
How the study worked
Researchers created 8mm full-thickness dorsal skin wounds in C57BL/6J mice and randomized them into control and acupuncture groups. The acupuncture group received daily 20-minute manual needling at four locations around the wound for 10 days. To test CGRP's role, some mice received the CGRP receptor antagonist BIBN4096 before each treatment. Wound repair was assessed via histology (H&E and Masson's staining), macrophage polarization was measured by flow cytometry and immunofluorescence, and cytokine levels were quantified by ELISA and RT-qPCR.
What this study cannot tell us
This was a mouse study using a specific wound model, and results may not directly translate to human wound healing. The acupuncture protocol was standardized for research but may differ from clinical practice. The additional non-CGRP pathways contributing to anti-inflammatory effects were not identified. Sample sizes per group were not specified in the abstract. The 10-day observation window may not capture long-term healing outcomes.
How to read the evidence
This is a preclinical animal study with a rigorous mechanistic design including receptor antagonist controls. While the evidence is well-controlled for a mouse study, human translation has not been tested.
When this study was published
Published in 2025, this is a very recent study representing current understanding of neuropeptide-immune interactions in wound healing and the first detailed mechanistic characterization of CGRP's role in acupuncture-mediated tissue repair.
The bigger picture
This study bridges neuroscience and immunology by showing how a neuropeptide — CGRP — mediates communication between nerves and immune cells during wound repair. The finding that CGRP drives macrophage reprogramming adds to growing evidence that the nervous system actively directs wound healing. This has implications beyond acupuncture: any intervention that stimulates local CGRP release could potentially accelerate healing, and understanding the additional CGRP-independent pathways could reveal new therapeutic targets.
Questions still open
- Could direct CGRP administration to chronic wounds replicate acupuncture's healing benefits without the needling?
- What are the additional non-CGRP neuropeptide pathways that contribute to acupuncture's anti-inflammatory effects?
- Would this CGRP-mediated mechanism also apply to diabetic wounds, which are notoriously slow to heal?
Common questions
What is CGRP and how does it help wounds heal?
Does this prove acupuncture works for wound healing in people?
Read the original research
Acupuncture accelerates wound healing via CGRP-RAMP1-TSP1-mediated macrophage M2 polarization.
Chinese medicine, 20(1), 192
Citation
Liu, Xiaoer; Chen, Junsheng; Zou, Lingyue; Lu, Xiaohan; Zhu, Boran; Li, Jingwen; Zhu, Yuyan; Jiang, Minjiao; Peng, Rou; Guo, Yifan; Lu, Shengfeng. (2025). Acupuncture accelerates wound healing via CGRP-RAMP1-TSP1-mediated macrophage M2 polarization.. Chinese medicine, 20(1), 192. https://doi.org/10.1186/s13020-025-01255-2