Protectin DX resolves fracture-induced postoperative pain in mice via neuronal signaling and GPR37-activated macrophage efferocytosis Article Swipe
Yize Li
,
Sangsu Bang
,
Jasmine Ji
,
Jing Xu
,
Min Lee
,
Sharat Chandra
,
Charles N. Serhan
,
Ru-Rong Ji
,
Yize Li
,
Sangsu Bang
,
Jasmine Ji
,
Jing Xu
,
Min Lee
,
Sharat Chandra
,
Charles N. Serhan
,
Ru-Rong Ji
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.11.10.687700
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.11.10.687700
Protectin DX (PDX) is a member of the superfamily of specialized pro-resolving mediators (SPMs) and exerts anti-inflammatory actions in animal models; but the specific signaling pathways involved in its actions have not been fully elucidated. Here we demonstrate the analgesic actions of PDX in a mouse model of tibial fracture-induced postoperative pain (fPOP) via activation of GPR37. Intravenous early-phase and late-phase treatment of PDX (100 ng/mouse) effectively alleviated fPOP. Compared to protectin D1/neuroprotectin D1, DHA, steroid, and meloxicam, PDX produced superior pain relief. While dexamethasone and meloxicam prolonged fPOP, PDX shortened the pain duration. The analgesic effects of PDX were abrogated in Gpr37 −/− mice, which displayed deficits in fPOP resolution. PDX binds GPR37 and induces calcium responses in peritoneal macrophages. LC-MS-MS-based lipidomic analysis revealed that endogenous PDX levels were ∼10-fold higher than PD1 in muscle at the fracture site. PDX promotes macrophage polarization via GPR37-dependent phagocytosis and efferocytosis through calcium signaling in vitro , and it further enhances macrophage viability and efferocytosis in vivo via GPR37. Finally, PDX rapidly modulates nociceptor neuron responses by suppressing C-fiber-induced muscle reflex in vivo and calcium responses in DRG neurons ex vivo and reducing TRPA1/TRPV1-induced acute pain and neurogenic inflammation in vivo . Our findings highlight multiple benefits of PDX to manage postoperative pain and promote perioperative recovery.
Related Topics
Concepts
Efferocytosis
Medicine
Inflammation
Phagocytosis
Nociceptor
Pharmacology
Macrophage
Microglia
Analgesic
Dorsal root ganglion
Calcium
Nociception
Autacoid
Meloxicam
Proinflammatory cytokine
Hyperalgesia
Threshold of pain
Signal transduction
Cordotomy
Prostaglandin
Endogeny
Apoptosis
Agonist
TRPV
Downregulation and upregulation
Neuroprotection
Reflex
Staurosporine
Anesthesia
Neuroscience
Internal medicine
Endocrinology
Metadata
- Type
- article
- Landing Page
- https://doi.org/10.1101/2025.11.10.687700
- https://www.biorxiv.org/content/biorxiv/early/2025/11/12/2025.11.10.687700.full.pdf
- OA Status
- green
- References
- 69
- OpenAlex ID
- https://openalex.org/W7105025429
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W7105025429Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2025.11.10.687700Digital Object Identifier
- Title
-
Protectin DX resolves fracture-induced postoperative pain in mice via neuronal signaling and GPR37-activated macrophage efferocytosisWork title
- Type
-
articleOpenAlex work type
- Publication year
-
2025Year of publication
- Publication date
-
2025-11-12Full publication date if available
- Authors
-
Yize Li, Sangsu Bang, Jasmine Ji, Jing Xu, Min Lee, Sharat Chandra, Charles N. Serhan, Ru-Rong Ji, Yize Li, Sangsu Bang, Jasmine Ji, Jing Xu, Min Lee, Sharat Chandra, Charles N. Serhan, Ru-Rong JiList of authors in order
- Landing page
-
https://doi.org/10.1101/2025.11.10.687700Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2025/11/12/2025.11.10.687700.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2025/11/12/2025.11.10.687700.full.pdfDirect OA link when available
- Concepts
-
Efferocytosis, Medicine, Inflammation, Phagocytosis, Nociceptor, Pharmacology, Macrophage, Microglia, Analgesic, Dorsal root ganglion, Calcium, Nociception, Autacoid, Meloxicam, Proinflammatory cytokine, Hyperalgesia, Threshold of pain, Signal transduction, Cordotomy, Prostaglandin, Endogeny, Apoptosis, Agonist, TRPV, Downregulation and upregulation, Neuroprotection, Reflex, Staurosporine, Anesthesia, Neuroscience, Internal medicine, EndocrinologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
-
69Number of works referenced by this work
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