Tuina Attenuates Pain with Reduced Serum Pain- and Inflammation-Related Mediators and p38 MAPK Phosphorylation in Selected Brain Regions in Rats with Knee Osteoarthritis.

PURPOSE: To investigate the effects of tuina on pain-related behaviors, serum pain- and inflammation-related mediators, and p38 mitogen-activated protein kinase (p38 MAPK) immunoreactivity in selected brain regions in rats with knee osteoarthritis (KOA). METHODS: Forty male Sprague-Dawley rats were initially randomized to a blank group (n = 10) and a KOA modeling cohort (n = 30). After successful model induction, the 30 modeled rats were randomized to the model, tuina, and drug groups (n = 10 per group). KOA was induced by intra-articular injection of L-cysteine-activated papain combined with treadmill training. The tuina group received tuina intervention, the drug group received celecoxib, and the blank and model groups received normal saline. Joint function and mechanical hypersensitivity were assessed using the modified Lequesne MG score and mechanical withdrawal threshold (MWT). Serum calcitonin gene-related peptide (CGRP), substance P (SP), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) were measured by ELISA. Phosphorylated p38 MAPK (p-p38 MAPK) immunoreactivity in the periaqueductal gray, nucleus accumbens, amygdala, and habenular nucleus was assessed by immunohistochemistry. RESULTS: KOA rats showed impaired joint function, reduced MWT, increased serum CGRP, SP, COX-2, and PGE2 levels, and elevated p-p38 MAPK immunoreactivity in the selected brain regions. Tuina and celecoxib both improved Lequesne MG scores and MWT, with no significant difference between the two interventions. Tuina reduced all four serum mediators, whereas celecoxib reduced only CGRP and SP, with no significant differences observed for COX-2 or PGE2. Serum CGRP, SP, and COX-2 levels were lower in the tuina group than in the celecoxib group. Both interventions reduced p-p38 MAPK immunoreactivity in the selected brain regions. CONCLUSION: Tuina improved pain-related behaviors and joint function in KOA rats. These effects may be associated with reductions in serum pain- and inflammation-related mediators and decreased p-p38 MAPK immunoreactivity in selected brain regions.