Effects of Combined Shinbaro and Celecoxib in a Complete Freund's Adjuvant-Induced Inflammatory Pain Mouse Model

Persistent inflammation resulting from injury, infection, or arthritis contributes to both peripheral and central sensitization. Various combinations of natural extracts have been explored to minimize the side effects associated with conventional medications. Shinbaro, which has traditionally been used in Eastern medicine to treat inflammatory conditions, was chosen due to its known anti-inflammatory properties. However, previous studies have not yet investigated the combined administration of celecoxib and Shinbaro for their anti-inflammatory and analgesic effects. In this study, we examined the anti-inflammatory and analgesic effects of combining celecoxib with Shinbaro in a complete Freund's adjuvant (CFA)-induced inflammatory pain model.

We randomly assigned 66 mice to 6 groups (n = 11 per group) and administered intraplantar injections of 100 μL CFA or saline into their right hind paw, followed by oral administration of Shinbaro (100 mg/kg), celecoxib (15 or 30 mg/kg), or both 30 minutes later. Behavioral assessments were conducted blindly at baseline and on days 1, 3, and 7 post-injection. The right hind paw and spinal cord were harvested 3 days post-injection to examine the molecular mechanisms, including macrophage infiltration in the right hind paw, as well as glial cell activation and inflammatory cytokine levels in the spinal cord. Statistical analysis was performed using Tukey's post-hoc test.

The combination of Shinbaro (100 mg/kg) and celecoxib (15 mg/kg) synergistically reduced mechanical hyperalgesia and paw edema by preventing the conversion of monocytes to macrophages and inhibiting macrophage infiltration. Moreover, it decreased the expression of pro-inflammatory cytokines and mediators in the spinal cord by inhibiting spinal microglial activation.

The combination of Shinbaro and celecoxib demonstrates significant anti-inflammatory and analgesic effects, suggesting its potential for managing inflammatory pain with fewer side effects than conventional therapies.