Amniotic Tissue Modulation of Knee Pain-A Focus on Osteoarthritis.

The use of intra-articular therapies as sources of growth factors, anti-inflammatory mediators, and medicinal signaling cells for osteoarthritis (OA) is rapidly evolving. Amnion, chorion, amniotic fluid, and the umbilical cord are distinct placental tissues that have been investigated for use in OA. Amniotic membrane (AM) synthesizes a variety of growth factors, cytokines, and vasoactive peptides that modulate inflammation. In addition, they contain amniotic epithelial cells and amniotic mononuclear undifferentiated stromal cells, which have chondrogenic and osteogenic differentiation capacity. AMs are also rich sources of hyaluronic acid and proteoglycans, which could play a role in the potential therapeutic relief of OA. Currently, there are several commercially available formulations of AM that differ based on content as well as how they were preserved. Understanding the processing of amniotic tissue is important because of their distinct mechanical and biologic effects of preservation on AM grafts. To date, there have been two preclinical and only one clinical study on the use of AM for OA, which show promising results. Many high level of evidence clinical trials are currently underway investigating the use of AM of OA. Future basic science and clinical research is warranted to better understand the anti-inflammatory and chondroregenerative properties of amniotic tissue and to determine clinically what amniotic tissue product is most efficacious for symptomatic OA.

Autologous protein solution prepared from the blood of osteoarthritic patients contains an enhanced profile of anti-inflammatory cytokines and anabolic growth factors.

The objective of this clinical study was to test if blood from osteoarthritis (OA) patients (n = 105) could be processed by a device system to form an autologous protein solution (APS) with preferentially increased concentrations of anti-inflammatory cytokines compared to inflammatory cytokines. To address this objective, APS was prepared from patients exhibiting radiographic evidence of knee OA. Patient metrics were collected including: demographic information, medical history, medication records, and Knee Injury and Osteoarthritis Outcome Score (KOOS) surveys. Cytokine and growth factor concentrations in whole blood and APS were measured using enzyme-linked immunosorbent assays. Statistical analyses were used to identify relationships between OA patient metrics and cytokines. The results of this study indicated that anti-inflammatory cytokines were preferentially increased compared to inflammatory cytokines in APS from 98% of OA patients. APS contained high concentrations of anti-inflammatory proteins including 39,000 ± 20,000 pg/ml IL-1ra, 21,000 ± 5,000 pg/ml sIL-1RII, 2,100 ± 570 pg/ml sTNF-RI, and 4,200 ± 1,500 pg/ml sTNF-RII. Analysis of the 82 patient metrics indicated that no single patient metric was strongly correlated (R(2) > 0.7) with the key cytokine concentrations in APS. Therefore, APS can be prepared from a broad range of OA patients.

Evidence-based approach of treatment options for postoperative knee pain.

Optimal pain management is critical after knee surgery to avoid adverse events and to improve surgical outcomes. Pain may affect surgical outcomes by contributing to limitations in range of motion, strength, and functional recovery. The causes of postoperative pain are multifactorial; therefore, an appropriate pain management strategy must take into account preoperative, intraoperative, and postoperative factors to create a comprehensive and individualized plan for the patient. Preoperative assessment includes management of patient expectations, recognition of conditions and early counseling for high-risk patients (ie, opioid dependence, psychiatric comorbidities), and use of preemptive analgesia techniques (ie, preoperative IV medications, peripheral nerve blocks, incisional field blocks). Intraoperative strategies include meticulous surgical technique, limiting the use of tourniquets (ie, duration and pressure), and using preventive analgesia methods (ie, postoperative field block, continuous nerve catheters, intra-articular injection). Postoperative analgesia may be facilitated by cryotherapy, early mobilization, bracing, and rehabilitation. Certain modalities (ie, continuous passive motion devices, transcutaneous electrical nerve stimulation units, iontophoresis) may be important adjuncts in the perioperative period as well. There may be an evolving role for alternative medicine strategies. Early recognition and treatment of exaggerated postoperative pain responses may mitigate the effects of complex regional pain syndrome or the development of chronic pain.

Pulsed electrical stimulation in patients with osteoarthritis of the knee: follow up in 288 patients who had failed non-operative therapy.

BACKGROUND: Optimized pulsed electrical stimulation (PES) regulates chondrocyte genes, enhances production of cartilage matrix materials, and inhibits production of matrix catabolic factors. METHODS: This prospective, cohort study examined the use of a PES device in treatment of knee osteoarthritis (OA) in patients who had failed non-operative therapy. Primary outcome measures were patient and physician global evaluation, and patient assessment of knee pain. RESULTS: This study included 288 (95 men, 193 women) patients who used the device from 16 to more than 600 days (mean: 889 hours). Improvement in all efficacy variables (p < 0.001) occurred. A dose-response relationship between effect size and hours of usage was observed as cumulative time increased to more than 750 hours. Improvement in patient or physician global occurred in 59.0% of patients who used it less than 750 hours, and for 73.0% of those who used it more than 750 hours. An economic analysis of a sub-group of patients showed that 45.3% reduced nonsteroidal anti-inflammatory drug (NSAID) use by 50.0% or more. CONCLUSIONS: A highly optimized PES device successfully attenuated knee OA symptoms in patients who had failed non-surgical therapy. Less than 250 hours of therapy provided relief, but improvement increased in a dose-response manner after 750 hours of cumulative use.