The Role Of Platelet Rich Plasma In Pain Management And Decrease In Opioid Use

Platelet-rich plasma, also known as PRP, has become increasingly popular for the treatment of orthopedic injuries and symptomatic pain that results from such injuries. By promoting a localized inflammatory response, PRP injections increase blood flow to the injured area and expedite the healing process, thereby leading to pain relief. PRP has the potential to be a key player in the future of pain management. However, current evidence of the impact of PRP on pain relief is controversial. This paper aims to review the most current randomized controlled trials evaluating the efficacy of PRP in pain relief in a variety of orthopedic injuries and diseases. THE ROLE OF PLATELET RICH PLASMA IN PAIN MANAGEMENT 3 Today’s America is confronting an epidemic involving the prescription of opioids for chronic pain. This trend started in the late 90’s when pharmaceutical firms began to advertise the use of opioids for non-cancer related chronic pain as a safe alternative (Asim & Juurlink, 2016). Americans experienced a cultural shift in the way pain was viewed and treated. Individuals suffering from chronic pain began to seek opioids in order to achieve pain relief and primary physicians continued to prescribe it. Two decades later, opioid related morbidity and mortality has increased dramatically leading the US Department of Health and Human Services (HHS) and the Centers for Disease Control and Prevention (CDC) to declare the current practice of opioid prescription and the related overdoses an epidemic (Asim & Juurlink, 2016). As professionals who regularly manage pain, anesthetists have an important role in combating overutilization of opioids. Furthermore, alternative and non-opioid methods to treat pain should be explored and incorporated into the anesthetist’s practice. Platelet-rich plasma (PRP) has been proposed to decrease pain in patients suffering from musculoskeletal injury and osteoarthritis. Regenerative medicine has adopted this therapy for its ability to produce cell proliferation, healing and consequently, pain relief. With the ability to relieve pain, PRP has the potential to change the future of pain management therapies and reverse the trend of increased opioid use experienced over the last twenty years. Platelet’s Role in Cell Regeneration Platelets are typically known for their contribution to coagulation and hemostasis. However, these intriguing cells serve several roles in addition to controlling bleeding. As first responders, platelets are the earliest cells to arrive in damaged tissue sites. When activated, they can release more than 300 substances that act in favor of tissue restoration including cytokines, chemokines and growth factors (Goleniewska & Poole, 2014). In addition, platelets recruit THE ROLE OF PLATELET RICH PLASMA IN PAIN MANAGEMENT 4 mesenchymal stem cells (MSC) and tissue smooth muscle cells to migrate towards the injured cells. Examination of the dynamic mechanisms of platelets sheds light as to how they may function as a component of PRP in pain management. Platelets, or thrombocytes, are complex anucleated cells derived from bone marrow cells called megakaryocytes. They are composed of an outer phospholipid cell membrane containing glycoproteins, glucosaminoglycans, and coagulation proteins. Microtubules of actin and myosin form a supporting structure, which is responsible for maintaining the platelet shape. The lack of nucleus makes it infeasible for these cells to reproduce. The energy source for these cells comes from their mitochondria and enzymatic system, which is capable of producing adenosine diphosphate (ADP) and adenosine triphosphate (ATP). In addition, they contain two specific types of granules, alfa and gamma, that are responsible for mediating hemostasis. Alfa granules contain fibrinogen, von Willebrand factor (vWF), fibronectin, factors V and VIII, plateletderived growth factors (PDGF), transforming growth factor-alfa (TGF-alfa) and thrombospondin. Gama-granules contain ADP and ATP, ionized calcium, histamine, serotonin and epinephrine (Grossman & Porth, 2014). Under physiological circumstances, platelets remain intact, circulating near the vascular wall. Once the endothelial wall is damaged, platelets are activated to secrete their bioactive contents precipitating a cascade of events and signaling, which ultimately culminates into clot formation and hemostasis. Platelets can also be activated by G-protein coupled receptor (GPCR) signaling from substances forming at the site of the thrombus (Goleniewska & Poole, 2014). In addition to immediate response to disrupted tissue, platelets have a fundamental role in communicating and modulating immunological response, therefore establishing a balance between tissue repair and tissue damage. Chemokines released by activate platelets induce the THE ROLE OF PLATELET RICH PLASMA IN PAIN MANAGEMENT 5 recruitment and proliferation of adult stem cells such as CD34-positive progenitor cells, mesenchymal stem cells (MSC), and smooth muscle cells (SMC) and endothelial progenitors, which are important in the process of regulation of apoptosis and cell survival. In a study investigating myocardial regeneration after an infarct, the authors found that injections of progenitor bone marrow cells, derived from both bone marrow and circulating blood, prevented both cardiac cell apoptosis and ventricular remodeling, and reestablished cardiac function (Assmus et al., 2006). Hepatocyte growth factor (HGF), which can also be released by platelets, is considered one of the mediators responsible to MSC migration to damaged cardiac tissue. Therefore, the release of HGF appears to be the mechanism by which platelets mediate the movement of MSCs to targeted areas of injury (Goleniewska & Poole, 2014). In the role of cell apoptosis, platelets can regulate the balance between cell death and survival. One of the pathways involving apoptosis is promoted through a cytokine called tumor necrosis factor (TNF). Platelets contain several TNF related ligands including CD-95, DC154, Apo2-L, Apo3-L and LIGHT, which potentially regulate apoptosis through signals from nearby cells. In addition, platelets have the ability to release high mobility group box 1 (HMGB1), a protein released by necrotic cells that regulates immune response and cell death (Gawaz & Vogel, 2013). Anti-apoptotic properties are another way in which platelets can promote tissue repair. This mechanism is exerted through anti-apoptotic activity of several mediators including the previously mentioned HGF, stromal cell-derived factor 1(SDF-1), serotonin, ADP and HMGB1 (Gawaz & Vogel, 2013). Gawaz and Vogel (2013) explain that whether a platelet will induce or inhibit apoptosis will depend on the amount of receptors and surface expression presented by that specific cell along with particularities of the target cell. THE ROLE OF PLATELET RICH PLASMA IN PAIN MANAGEMENT 6