How APFD Works
Pain is the body’s warning system.
Injury/inflammation is characterized by increased vascular permeability and fluid exudation; free radical damage; infiltration by neutrophils and phagocytes with a release of damaging lysosomal enzymes, cytokines and chemokines; activation of the arachidonic acid cascade with production of pro-inflammatory prostaglandin E2 and leukotrienes via the cyclo-oxygenases (COX-1 and COX-2) proliferation (which also can destroy ECS anti-inflammatory receptor enzyme properties) and lipoxygenase; changes in neuronal receptors, ion channels, proteins; release of pro-inflammatory mediators; and mast cell release of the biogenic amines bradykinin, histamine, and serotonin; all these processes acting to expand and perpetuate tissue injury and pain. The ingredients selected for APFD focus on each of these elements of the pain-inducing, tissue-damaging inflammatory process.

One of the main causes of ongoing tissue damage is the generation of highly reactive molecular species called free radicals, such as superoxide and hydroxyl ions. Free radicals cause cellular membrane damage by lipid peroxidation. The main mechanism controlling free radical damage is the scavenging and inactivation of these radicals by the family of enzymes, Superoxide Dismutase (SOD). SOD consists of three isoforms based on the trace element that forms the enzyme’s active site. These SOD isoforms exist as pro-enzymes until they are activated by the insertion of the specific trace element into the active site. The SODs consist of a copper-zinc isoform (most abundant), a copper isoform, and a manganese isoform (mitochondrial). In the body, when injury or inflammation occurs, copper and zinc complexed with amino acids or protein are mobilized from the liver and transported to the site of inflammation. APFD, using an orthomolecular treatment approach, enhances this physiologic mobilization response by delivering, to the site of injury, each of the required trace elements complexed with an amino acid (in a form which can be immediately used by the body) to help activate the SODs  These organically complexed trace element-amino acid complexes can be immediately inserted into the SOD active sites and convert the pro-enzyme form to a physiologically active functional enzyme that can limit tissue damage.  When activated, these enzymes convert the charged, highly reactive superoxide radicals into non-reactive hydrogen peroxide, thus preventing further tissue damage.

There is pre-and post-clinical trial data and research supporting the proposed model for interaction of Mn, Cu and Zn-amino acid complexes with SOD, as designed for this product. This is researched data. These organically complexed trace elements, in APFD, also have beneficial effects in the control of inflammation by stabilizing lysosomal membranes in the infiltrating phagocytes, thus limiting the release of tissue damaging enzymes such as proteases, lipases, and hyaluronidase. Finally, these complexes stabilize tissue mast cell membranes, limiting the release of histamine and serotonin, thus reducing vascular permeability and fluid transudation into the injured tissues. This results in helping reduce swelling, redness, and pain, and a speeding of healing. APFD is the first and only topical product that contains and can deliver these complexes directly to the affected areas. Its published clinical trial, from Tufts University, backs up its safety and effectiveness.

Along with the enzymes like SOD, the added nonenzymatic equivalents also fight the increased production of reactive oxygen species resulting from injury, which deplete the endogenous scavenging compounds.
Additional natural scavengers and powerful antioxidants, with anti-inflammatory chemical messengers, physiological regulators, and cell cycle inhibitors, have been shown to induce protection for the body against the reactive oxygen species (ROS), whose accumulation plays a pivotal role in suppression of NF-κB (nuclear factor kappa-light chain-enhancer of activated B cells) and by the suppression of SOD activity. The NF-κB family of transcription factors has an essential role in inflammation and innate immunity.

ROS are significant signaling molecules in the progression of inflammatory disorders. There is enhanced ROS generation by polymorphonuclear neutrophils (PMNs), at the site of trauma/inflammation produced by injury, which causes endothelial dysfunction and tissue injury. This is another part of the oxidative stress mechanism that leads to tissue damage, inflammation, pain; and these are areas of concern that can utilize some direct intervention with APFD, to limit the progression.

The NF-κB family of transcription factors is an essential mediator in inflammation. Deregulated NF-κB activation contributes to the pathogenic processes, of various inflammatory diseases.
Examining how this processes advances, with the inflammatory response and tissue injury which causes pain, a selection of natural botanical components have been added, which can add support, by limiting this progression and aiding the body in a natural course of healing. Building natural components into the formula, for the activation and function of NF-κB to work as a part of controlling inflammatory diseases, provides an additional pathway to help facilitate in inhibiting the inflammation and pain.

Activity studies, on various analogs of the APFD product, reveal that its high number of ortho-methoxy substitutions and the high level of hydrogenation of the heptadiene parts, can offer some radical scavenging potential. This is further supported by including ingredients that serve as inhibitory neurotransmitters.

Another look at the pain and inflammatory process shows that the 5-lipoxygenase (5-LOX) pathway is also involved, generating leukotrienes (LTs), LTB4 and cysteinyl LTs. Osteoblasts synthesizing LTs also stimulate and enhance the production of interleukin 1, tumor necrosis factor α, and various other cytokines that are potent TNF. Added to the product are elements set to target and block some of these 5-LOX inflammatory mediators.

The ECS is a complex signaling network where different proteins play distinct roles, significantly regulating the homeostatic processes that involves pain and inflammation. This product’s select endocannabinoid active phytopharmaceutical ingredients encompass modulators/agonists of the anti-inflammatory receptors (CB-2) exhibiting direct functioning effects; indirect pain antagonist (CB-1 receptors without CNS effects); the systems therapeutic targeting inhibitors (FAAH regulatory metabolic and catabolic enzymes); allosteric modulators, other modulators that affect the endogenous AEA cellular reuptake mechanism, and TRPV1 agonists. These natural products can bind and functionally interact at various points along the ECS, targeting enzymes and protein receptors, selectively and indirectly triggering components of the G-protein-coupled CB1 receptors, and improving the anti-inflammatory modulating CB2 receptors. Of importance is the prominence of the activity of the select components, through the various mechanisms of the EDS system that provide anti-inflammatory properties and others that reduce the metabolic production of COX-2 overexpression, which induces ECS cell death.

Results: by using innovative technology, intense research around the body’s pain/inflammatory systems, a novel approach utilizing the synergy of mechanisms built on strong science, and employing an orthomolecular treatment model, this analgesic evolved to aid in the reduction of pain and stiffness by addressing multiple mechanisms of the entire pain cascade—naturally, safely, effectively.

This analgesic looks to address the problems of the disease state, not just the symptoms.
A few additional items of interest regarding this product, which distinguishes it from other analgesics, besides the scrutiny of a clinical trial and patent, may be of interest. These particulars, which are of significance, come from the Tufts’ Clinical Trial data, patient usage accounts, and reports from practitioners.
The clinical trial study population embodied two separate and distinct pathologies: joint pain and muscle pain. The study reported that this analgesic could be used as a first line (as it was in the study) or adjunct treatment for the relief of pain. Resolution of the aforementioned pain was without intervention, in some showing a 68% decrease in pain, from baseline, at period 2. Consider a patient pain scale rated at 8 going to 4, or a 6 going to 3, and how much would have been gained in function. One should also take into consideration the severity of the chronic disease state of the TMJD trial assemblage and how cleanly the trial results came out. It was a most difficult group of tertiary level patients with irrepressible pain management problems associated with their disease, who obtained relief using only the APFD product. Tufts designed the statistical data that is in the trial results.
The study applicability, using TMJD and masseter muscle pain patients would generally be considered nociceptive pain (generated from inflammation due to injury), but because these were long-term chronic pain patients, we may extrapolate that there could have been some components of neuropathic pain involvement in the study group, though not defined or discussed. This analgesic product has been used successfully for neuropathic pain (post herpetic neuralgia, diabetic neuropathy, etc.).

When setting out to develop a product that is distinctive in its action and more effective and safer, to treat a chronic problem or disease state, the approach needs to be divergent. It is the understanding of the pain process that has led to the structuring of this analgesic and the selection of its natural ingredients. The product was constructed to assists the body by providing it with natural elements which the body recognizes and can quickly utilize to help fight inflammation, pain, and stiffness.
The relative roles of the various formulation components showed some unique outcomes, distinctive from what is seen with the usual simple counter-irritant analgesic or topical anesthetic. These distinctive outcomes have been reported by members of the clinical trial team, healthcare professionals, and anecdotal reports from persons using the product, for all types of pain.

Examine the product from outcomes/results based and proof of theory methodology—today’s measure of clinical acceptability:
The trial group, with exceptionally severe problems, showed that there was a clear picture of pain control. Many diverse types of pain management approaches had been previously tried with these patients. The Tufts results were a measurement and a confirmation of what was seen anecdotally with the product, for all types of pain relief. This was proof of concept. The theoretical formulation of selected ingredients that could play active parts in addressing the different segments of the pathway of the pain cascade were merged to provide meaningful outcomes.

Now, adapt the evidence/results-based process measures, in healthcare analytics, for this product:
Outcome measures: These are the high-level clinical and financial outcomes that concern healthcare.
Balance measures: These are the metrics a health system must track to ensure that an improvement in one area is not negatively impacting another area.
Process measures: These measures are the specific steps in a process that lead, either positively or negatively, to a particular outcome metric and shows an opportunity for healthcare process improvement.
Finally, the anecdotal and trial outcomes were significant and far exceeded many current treatments, Rx and OTC, surpassing evidence/results-based process measures.
Outside of the study, there was found to be faster/shorter healing times when injury (strain, sprains, RSI, etc.) are involved. With athletes who have used the product as a warm-up cream, endurance was increased, from components delivered by the product that helped decrease lactic acid buildup and muscle spasms. Athletes also had faster healing times post traumatic or stress injuries. Unlike counter-irritant topical analgesics, another differentiating point is that only a small amount of cream needs to be applied, to provide pain relief.

APFD offers a balance of safety and efficacy in the treatment and management of pain and stiffness; eliminating many significant hazards of some drug treatments, adding safe and effective first-line or complimentary treatment. The product shows evidence based, best practice standards and positive measurable process improvement in its clinical trial and with patient use, for pain management, meeting the SMART treatment goals.
Of all the nonopioid analgesics, this product shows the most noteworthy evidence based on best practice standards, and positive measurable process improvement in the clinical trial, and with patient use for pain management, meeting the SMART treatment goals. This product presents a great opportunity for healthcare and pain management improvement.

A Structure Process Outcome framework was developed, by Dr Avedis Donabedian. “Structure describing the presence of something that is reasonably associated with quality. Process refers to the actions associated with quality, like drug utilization review procedure and how often the procedure is followed could be thought of as a process measure. Outcomes are the end results attributable to healthcare products or services. Positive outcomes associated with quality healthcare include reduced mortality, improved quality of life,” control of disease and pain, and patient participation and satisfaction with care.

Putting this together: quality outcomes, for a patient with pain, can be measured by safe pain control. To structure and enhance effective pain management, adding APFD into every pain patient’s process is easy, safe, and has been shown to improve quality outcomes.
Pain management requires a consistent and comprehensive treatment program. The growing discipline of chronic and acute pain management requires the assembly of multimodal/multidisciplinary plans, individualized to a patient’s personal abilities and needs. With best practices revolving around quality improvement and quality of care, APFD has been shown to be effective in delivering safe pain relief for all types of pain. It can be easily integrated throughout every quality, multimodal team healthcare plan, be effective in delivering safe relief for all types of pain, shows benefits alone as a first-line or as an adjunct treatment, can be used for breakthrough pain, or with an opioid dose decreasing schedule or in a MAT program, and will lead to improved outcomes for pain patients and a pain free day.

Think of what A Pain Free Day looks like—Relief: Any Time, Any Place, for Any Pain Patient.
There are many areas where you can incorporate APFD into your patient’s pain management, to improve outcomes. Any patient receiving prescription opioids or other pain medications should be introduced to APDF, to help augment/enhance pain relief, or when slowly transitioning off pain medications. Any patient in need of an effective alternative, should be shown the advantages of APFD, as an optimum choice.

Please offer your patients the “For Your Patient” information on this site​

​Patients can look to paintoolkit.org, for more information.
Harvard University has put together a booklet on pain relief without drugs or surgery, plus other important information, which can be found at:
https://www.health.harvard.edu/special-health-reports/pain-relief-natural-and-alternative-remedies-without-drugs-or-surgery
Topical analgesics, like APFD, are considered a non-drug approach.
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Copyright 2021

About Pain: Tissue injury and subsequent inflammation represent a complex series of pathophysiological events resulting in the characteristic signs of heat, redness, swelling, pain and stiffness. Inflammation is present in virtually all pain syndromes, which includes arthritis, bursitis, tendonitis, muscle sprains and strains, low back pain, TMJ disorder, and RSI such as carpal tunnel syndrome, and with neuralgias. Trauma, damage, over-use diseases are types of injuries to the body that provoke the inflammatory process. There is subjective pain sensation at the site of injury with nerves detecting changes in the tissue. Then there is sensory pain discrimination, from  tissue injury that is a result of the release of multiple inflammatory mediators. Inflammation impacts many pain pathways, resulting in pain sensation and leading to the damaging of cells at the site of injury. The multifocal deliverers of pain need a synergistic, multimodal approach to dispense  analgesia.