Although chronic pain affects about 1% of the US population, it remains largely resistant to treatment. Despite great variability in pain outcomes, the application of autologous platelet-rich plasma (PRP) has become increasingly popular in attempts to reduce chronic pain. The variability in PRP efficacy raises the question of whether PRP actually has an analgesic capacity, and if so, can that capacity be made consistent and maximized. The best explanation for the variability in PRP analgesic efficacy is the failure during PRP preparation and application to take into account variables that can increase or eliminate its analgesic capabilities. This suggests that if the variables are reduced and controlled, a PRP preparation and application protocol can be developed leading to PRP inducing reliable, complete, and long-term pain relief. The goal of this study was to examine some of the variables that influence platelets and see how they might be controlled to increase the analgesic potential of PRP. Among the variables examined are the physiological status of the patient, methods used to prepare PRP, and methods of PRP application. The goal of modifying these variables is to minimize platelet serotonin content, maximize platelet content of factors that reduce inflammation and pain, while maintaining their bioactivity, maximize platelet capacity to aggregate at injury sites, induce rapid and simultaneous release of their contents, and optimize PRP application protocols. It is concluded that controlling some or many of these variables will lead to PRP that induces reliable, maximum, and long-term relief of chronic pain.

About 1% of the US population suffers from chronic pain that is often severely debilitating and largely resistant to treatment. Although chronic pain is a major public problem, there is little available effective pain management, and there is still a lack of understanding of the fundamental mechanisms of pain and how pain can be reliably and safely reduced or eliminated. This paper looks at the application of platelet-rich plasma (PRP) to pain sites as a potential technique for reducing or eliminating chronic pain, and the variables that must be addressed if PRP is to achieve its potential of providing some to complete and permanent relief of chronic pain.

Platelets within PRP release a host of pro- and anti-inflammatory mediators that not only induce pain but also reduce inflammation and pain. These factors also alter the wound environment leading to tissue healing and regeneration via the complex effects of regulating stem cell in-migration, proliferation, differentiation, and anabolic/catabolic processes. These multiple functions have led to the use of PRP to stimulate the recovery of nonhealing injuries, typically associated with chronic pain, in fields including ear, nose, and throat, orthopedics, sports medicine, dentistry, neurosurgery, ophthalmology, urology, wound healing, cosmetic, cardiothoracic, and maxillofacial surgery.,

A number of clinical studies concluded that PRP provides little or no pain relief for tendinosis or rotator cuff tears. However, other clinical studies found that PRP reduces or eliminates pain, such as that associated with tendinosis, rotator cuff tears,, osteoarthritis, plantar fasciitis, and muscle injuries. PRP is also reported to act as an analgesic in animal pain models, such as rat tendinosis, rotator cuff injury, and dog tendon injury. In general, the findings of PRP analgesic influence led to the conclusion that although there are suggestions that PRP can act as an analgesic, the variability in study outcomes resulted from their small study sample sizes and the inclusion of too many variables, which did not allow the studies to be compared, or that the comparative analyses of the outcomes of different studies do not provide sufficient statistical support for the conclusion that PRP acts as an analgesic.

Two major variables proposed to account for the observed differences in PRP efficacy are PRP composition, which differs greatly depending on the device used to prepare PRP, and the method of PRP application. This has led to the suggestion that consistent analgesic results will only be seen once the variables associated with PRP preparation and application are reduced.

However, other variables must also be considered, each of which can exert significant influences on PRP composition and efficacy such as the: 1) physiological status of the individual from whom blood is drawn and on whom it will be applied; 2) platelet activation methods; and 3) types of tissues to which PRP is applied and injury type. These and other variables lead to >10-fold differences in platelet concentration within PRP, large differences in the type and concentration of factors within platelets, determine whether platelets aggregate and release their contents at the pain site, while also influences the concentration of factor released at the pain site, the rate of factor release, ratios of the released factors, and bioactivity levels of those factors. While any one variable can significantly alter PRP composition, multiple variables exert greater influences and can entirely block the analgesic efficacy of PRP.

One approach to developing a PRP preparation and application protocol that induces reliable, complete, and permanent pain relief is to determine the common variables associated with studies in which PRP induced good analgesia, and then perform new studies using those common variables. However, other variables that have so far not been considered must be taken into account, and adjusted to maximize the level of PRP-induced pain relief. This paper examines the influences of a number of the most salient variables associated with an individual’s physiological status, and methods for preparing and applying PRP, that affect the concentration of platelets in PRP, platelet factor content, concentration, bioactivity, and ratios, and how these variables can be adjusted to optimize the potential analgesic influence of PRP.

Keywords: analgesia, anti-inflammation, chronic pain, cytokines, inflammation, nerve trauma, neuropathic pain, platelet-rich plasma, pro-inflammation
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