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Updated: Jan 9, 2026
Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
Prostaglandins prevent long-lasting pain in a mouse model of chronic postsurgical pain
Mohamad Karaky1, Lucas V Lima1, Anahita Oveisi1
1Faculty of Dental Medicine and Oral Health Sciences, Department of Anesthesia, Faculty of Medicine, Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
Background:
Chronic postsurgical pain (CPSP) affects 5-85% of patients, depending on the surgery type, with minimal treatment options. A previous study showed that immune response inhibition by dexamethasone (DEXA) or NSAIDs in inflammatory pain assays in mice leads to pain prolongation, which can be reversed by injection of neutrophils or neutrophil-released S100A8/A9 proteins. Here we tested whether DEXA or NSAIDs similarly lead to prolonged pain in the mouse paw incisional assay, and if prostaglandin (PG) receptor agonists can prevent and resolve this pain through upregulation of S100A8/A9 in myeloid cells.
Methods:
CD-1 mice underwent plantar incision and were treated with DEXA, diclofenac, or saline. PG agonists (beraprost, treprostinil, or misoprostol) were administered postsurgery. Mechanical withdrawal thresholds were measured before and at multiple time points after incision injury. Neutrophils were depleted to confirm their involvement. Pathway validation was conducted using STAT3 and S100A8/A9 inhibitors and a STAT3 activator.
Results:
Saline-treated mice recovered within 2 weeks, whereas DEXA-treated mice experienced prolonged hyperalgesia for >10 weeks. PG agonists both prevented and reversed the DEXA-induced hyperalgesia. Depletion of neutrophils in DEXA-treated mice impaired the effect of treprostinil. Inhibiting STAT3 or S100A8/A9 delayed recovery, whereas STAT3 activation mimicked treprostinil's effect. Diclofenac produced similar effects on pain duration as DEXA, also in a treprostinil-reversible manner.
Conclusions:
We show that prostaglandin agonists can produce a surprising analgesic effect. Prostaglandin receptor agonists show promise in preventing and resolving CPSP by upregulating S100A8/A9 through the PKA-STAT3 pathway in innate immune cells, suggesting a new therapeutic approach for chronic postsurgical pain.
