Intra-articular Injection of Pure Platelet-Rich Plasma Is the Most Effective Treatment for Joint Pain by Modulating Synovial Inflammation and Calcitonin Gene-Related Peptide Expression in a Rat Arthritis Model

Abstract

Background: Platelet-rich plasma (PRP) has emerged as a treatment for osteoarthritis (OA). However, the effect that leukocyte concentrations in PRP have on OA remains unclear. Purpose: To clarify the optimal PRP formulation for OA treatment by comparing pure PRP, leukocyte-poor PRP (LP-PRP), and leukocyte-rich PRP (LR-PRP) in a rat arthritis model. Study Design: Controlled laboratory study. Methods: Knee arthritis was induced bilaterally in male Wistar rats with intra-articular injections of monosodium iodoacetate (MIA) on day 0. Rats were randomly assigned to 1 of 3 treatment groups (pure PRP, LP-PRP, and LR-PRP). On day 1, allogenic PRP was injected into the right knee of rats and phosphate-buffered saline was injected into the left knee as a control. Weight distribution on the hindlimbs was measured for 14 days to assess pain behavior. Rats were euthanized at day 5 or 14 for histological assessment of synovial tissue and cartilage. Immunohistochemical staining of calcitonin gene-related peptide (CGRP) and α-smooth muscle actin was performed to determine the mechanism of pain relief induced by the PRP preparations. Results: In all groups, PRP increased the load-sharing ratio on PRP-injected knees, with pure PRP eliciting the largest effect among the 3 kinds of PRP (P < .05). Structural changes in the synovial tissue were significantly inhibited in the pure-PRP group compared with the control group after both 5 and 14 days (P < .001 and P = .025, respectively), whereas no significant difference was found between the control, LP-PRP, and LR-PRP groups. An inhibitory effect on cartilage degeneration was observed only in the pure-PRP group on day 14. Pure PRP also significantly inhibited expression of CGRP-positive nerve fibers in the infrapatellar fat pad compared with the other groups (P < .05). Conclusion: In an MIA-induced arthritis model, pure PRP injection was the most effective treatment for reduction of pain-related behavior and inhibition of synovial inflammation and pain sensitization. Clinical Relevance: PRP formulations should be optimized for each specific disease. This study shows the superiority of pure PRP for treatment of arthritis and joint pain.