C-C motif chemokine ligand 12 (CCL12) is a critical chemokine driving postoperative pain
Source: Pain
Authors: Sabrina de Souza, Hannah Hua, Sophie Laumet, Jaewon Sim, Charlotte Vanacker, Alexis Bavencoffe, Geoffroy Laumet, Publication Date: Mon, 09 Mar 2026 06:00:00 -0400
Pain. 2026 May 1;167(5):1098-1109. doi: 10.1097/j.pain.0000000000003936. Epub 2026 Feb 27.
ABSTRACT
The development of persistent postoperative pain remains a major clinical challenge, partly because of limited understanding of the molecular mediators driving inflammation and pain after surgery. The interaction between the nervous and immune systems plays a critical role in the initiation and maintenance of pain, but immune mediators in this process remain poorly characterized. Targeting cytokines and chemokines represents an attractive strategy to regulate inflammation in both the peripheral and central nervous systems and to modulate pain. Here, we demonstrated that the understudied chemokine C-C motif chemokine ligand 12 (CCL12) is significantly elevated in surgically incised skin. Administration of recombinant CCL12 induced dose-dependent mechanical and thermal hypersensitivity in naïve mice. C-C motif chemokine ligand 12 acted directly on nociceptors to increase calcium influx and neuronal excitability in dissociated dorsal root ganglia neurons. Notably, neutralization of CCL12 reduced pain behaviors and prevented the development of hyperalgesic priming. Surprisingly, CCL12 did not modulate the immune response to incision. These findings suggest that CCL12 is a key mediator of postoperative pain and highlights its potential as a therapeutic target for improving pain management after surgery.
PMID:41800753 | DOI:10.1097/j.pain.0000000000003936
Pubmed ID: pubmed:41800753
Identifiers: pmid:41800753, doi:10.1097/j.pain.0000000000003936,
Paper chosen by Rajesh Khanna
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In this paper, the Laumet group identified CCL12 as a vital chemokine that drives postoperative pain by facilitating communication between the immune and nervous systems. Using a mouse model of surgical incision, the study found that CCL12 levels rise significantly in damaged skin, particularly within tissue-resident macrophages. The researchers demonstrated that this chemokine directly increases neuronal excitability and calcium influx in sensory neurons, leading to heightened mechanical and thermal sensitivity. Interestingly, the study discovered that CCL12 does not rely on the common CCR2 receptor to induce pain, nor does it alter the overall inflammatory immune response. Most importantly, neutralizing this chemokine effectively reduced acute pain and prevented the transition to chronic hypersensitivity, known as hyperalgesic priming. Consequently, the authors propose that targeting CCL12 offers a promising new therapeutic strategy for managing recovery after surgery.