Knee osteoarthritis (KOA) is a common, chronic, degenerative disease. Platelet-rich plasma (PRP) can significantly relieve KOA pain; however, the mechanism of PRP-induced analgesia remains to be studied. Macrophages are closely related to KOA pain, and regulating macrophage polarization may be an effective way to relieve KOA pain. Therefore, the aim of this study is: First, to explore whether PRP can effectively relieve pain in a KOA animal model and whether it relieves pain by regulating macrophage polarization. Second, to explore the mechanism by which PRP regulates macrophage polarization. Thirty-six healthy male SD rats were randomly divided into sham group, MIA group and PRP group. The KOA rat model was established by injecting 1 mg of MIA into the joint cavity. Behavioral tests, including weight-bearing asymmetry, hot plate, and von Frey hairs tests, were performed. The positive expression rates of inducible nitric oxide synthase (iNOS) and CD163 in the synovium were detected via immunohistochemical staining. Meanwhile, RAW 264.7 cells induced by lipopolysaccharide were treated with PRP in vitro. The production levels of the nuclear factor kappa-B (NF-κB) pathway-related proteins NF-κB p65, inhibitor-κ binding protein α (IκBα), p-NF-κB p65, p-IκBα and the iNOS and CD163 proteins were measured via western blotting. An enzyme-linked immunosorbent assay was used to detect the release of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), and nerve growth factor (NGF). The behavioral results revealed that PRP relieved pain. PRP reduced the proportion of M1/M2 macrophages among synovial macrophages, significantly inhibited the secretion of TNF-α and IL-1β in the synovium, and increased the secretion of IL-10. In addition, in vivo experiments revealed that PRP decreased the protein expression of iNOS, p-IκBα/IκBα, and p-p65/p65 and increased the protein expression of CD163. Furthermore, PRP decreased TNF-α, IL-1β, and NGF levels in RAW 264.7 cells and increased the secretion of IL-10. Our findings indicate that PRP can improve long-term relief from KOA pain. The analgesic mechanism promotes the transformation of M1 macrophages to M2 macrophages by inhibiting the NF-κB signaling pathway, which reduces the release of downstream pain-causing factors, thus relieving inflammation and pain.

Objective: This study aims to compare the efficacy of platelet-rich plasma and corticosteroids in treating plantar fasciitis, focusing on pain relief, foot function, and plantar fascia thickness to identify the optimal treatment approach. Design: A comprehensive search of medical databases was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, utilizing an extensive keyword strategy. Inclusion criteria encompassed prospective randomized controlled trials involving adult patients with plantar fasciitis treated with local platelet-rich plasma or corticosteroid injections, specifically assessing outcomes such as the visual analog scale, American Orthopedic Foot and Ankle Society scores, and plantar fascia thickness. Results: The meta-analysis included 24 randomized controlled trials with 1653 participants. Platelet-rich plasma injections yielded significantly better visual analog scale scores compared to corticosteroid injections at 3 mos (P = 0.03) and 6 mos (P < 0.001), with no significant differences at 1 mo (P = 0.12) and 12 mos (P = 0.08). American Orthopedic Foot and Ankle Society scores demonstrated that platelet-rich plasma was superior to corticosteroid at 3 (P = 0.05), 6 (P < 0.001), and 12 mos (P < 0.001), with no significant differences at 1 mo (P = 0.31). Regarding plantar fascia thickness, there were no significant differences between platelet-rich plasma and corticosteroid at 1–1.5 mos (P = 0.18), 3 mos (P = 0.64), and 6 mos (P = 0.05). Conclusions: Platelet-rich plasma injections offer superior pain control compared to corticosteroids in the medium term (3–6 mos) but not in the short term or at 1 yr.

Background: The development of neuropathic pain (NP) is one of the reasons why the pain is difficult to treat, and microglial activation plays an important role in NP. Recently, platelet-rich plasma (PRP) has emerged as a novel therapeutic method for knee osteoarthritis (KOA). However, it’s unclarified whether PRP has analgesic effects on NP induced by KOA and the underlying mechanisms unknown. Purpose: To observe the analgesic effects of PRP on NP induced by KOA and explore the potential mechanisms of PRP in alleviating NP. Methods: KOA was induced in male rats with intra-articular injections of monosodium iodoacetate (MIA) on day 0. The rats received PRP or NS (normal saline) treatment at days 15, 17, and 19 after modeling. The Von Frey and Hargreaves tests were applied to assess the pain-related behaviors at different time points. After euthanizing the rats with deep anesthesia at days 28 and 42, the corresponding tissues were taken for subsequent experiments. The expression of activating transcription factor 3 (ATF3) in dorsal root ganglia (DRG) and ionized-calcium-binding adapter molecule-1(Iba-1) in the spinal dorsal horn (SDH) was detected by immunohistochemical staining. In addition, the knee histological assessment was performed by hematoxylin-eosin (HE) staining. Results: The results indicated that injection of MIA induced mechanical allodynia and thermal hyperalgesia, which could be reversed by PRP treatment. PRP downregulated the expression of ATF3 within the DRG and Iba-1 within the SDH. Furthermore, an inhibitory effect on cartilage degeneration was observed in the MIA + PRP group only on day 28. Conclusion: These results indicate that PRP intra-articular injection therapy may be a potential therapeutic agent for relieving NP induced by KOA. This effect could be attributed to downregulation of microglial activation and reduction in nerve injury.

Knee osteoarthritis (KOA) is a major cause of disability in the elderly, with its pain primarily driving medical consultations. Despite numerous studies, the role of Vitamin D in managing KOA pain remains inconclusive. This study seeks to explore the association between serum Vitamin D levels and WOMAC pain scores, providing new insights into potential treatment strategies for KOA. Utilizing data from the Osteoarthritis Initiative (OAI) database, we conducted a cross-sectional analysis involving 524 participants. Serum levels of 25-hydroxyvitamin D were measured using liquid chromatography-tandem mass spectrometry. WOMAC pain scores served as the dependent variable. Multivariable linear regression models and restricted cubic splines were employed to assess the relationship between Vitamin D levels and KOA pain, with subgroup analyses stratified by sex. Higher Vitamin D levels were significantly associated with lower WOMAC pain scores in males across all models. For females, no significant associations were observed. The analysis suggests a nonlinear relationship between Vitamin D levels and KOA pain in the general cohort, which becomes non-significant after adjustment for covariates. Our findings indicate that Vitamin D is associated with reduced pain in male patients with KOA, highlighting a potential sex-specific therapeutic approach. The results warrant further investigation through longitudinal studies and randomized controlled trials to substantiate Vitamin D supplementation as a viable treatment for reducing KOA pain in males.