Dexamethasone reduces postoperative pain while delays wound healing in an animal model: Involvement of the NLRP3/Caspase-1/IL-1beta pathway

BMC Anesthesiol. 2026 Mar 26. doi: 10.1186/s12871-026-03780-5. Online ahead of print.

Background

Intravenous dexamethasone has been used clinically to reduce surgical pain. Our study aims to investigate the analgesic efficacy, optimal dosage, mechanisms, and effects on surgical wound healing of dexamethasone in an animal postoperative pain model.

Methods

We first converted 2 commonly used doses of dexamethasone in humans (8 mg and 16 mg) to their rat equivalent doses (0.24 mg and 0.47 mg). Rats then received hind paw incision with either saline, 0.24 mg or 0.47 mg dexamethasone injections. Subsequently, we compared degrees of mechanical and thermal allodynia by the Von Frey Test and the Thermal Place Preference Test. We then performed molecular tests and H&E staining of the hind paw sample to further determine dexamethasone’s effect locally. Blood glucose and body weight were also measured to delineate its systemic effect.

Results

Both 0.24 mg (p < 0.01) and 0.47 mg (p < 0.05) dexamethasone reduced postoperative mechanical and thermal pain in rats on postoperative day (POD) 1. NLRP3, pro Caspase 1, Caspase 1, pro IL-1β and IL-1β levels were significantly lower in both dexamethasone groups when compared to control (p < 0.05). Dexamethasone reduced the M1:M2 macrophage ratio at the incision site. To investigate dexamethasone’s effect on wound healing, bulk RNA sequencing was conducted, which revealed significant downregulation in mKi67. Immunofluorescence showed a dose-related decrease in Ki67 positive keratinocytes in the skin (p < 0.05). H&E staining demonstrated deceleration in wound healing in both doses of dexamethasone on POD1 (p < 0.05), but only 0.47 mg dexamethasone delayed wound healing on POD3 (p < 0.05). There were no gross differences in wound morphology between rats receiving saline, 0.24 mg, or 0.47 mg dexamethasone on POD7 and POD14. As for the systemic effects, there was no significant difference in blood glucose levels between the 3 groups (p > 0.05). There was significant weight loss in rats receiving dexamethasone (p < 0.05).

Conclusions

Although dexamethasone was effective in pain control, using a moderate dose was non-inferior to a high dose. However, use of higher doses was associated with slower wound healing. Hence, our results in an animal model of acute postoperative pain suggest that using a moderate dexamethasone dose (8 mg) in humans may provide a better balance between analgesic efficacy and effects on wound healing.

PMID:41888693 | DOI:10.1186/s12871-026-03780-5