PEA and Chronic Pain
Posted on Sep 04, 2020

Hi, Dr. Warner here again – 

Today I want to discuss the use of palmitoylethanolamide (PEA) for chronic pain and inflammation.

Neuroinflammation, or an inflammatory condition of the central nervous system, is now being thought of as the source of chronic pain. This is the common mechanism of many central nervous system (CNS) disorders. Chronic pain is one central nervous system disorder, as are Parkinson’s disease, Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s disease, and others.  

Most current pharmaceuticals and other treatments for pain follow a neuronal cell target plan – that is, they target the neurons themselves and not the supporting cells of the nervous system. The supporting cells are far more numerous.

Today, it is thought that the neuroinflammation causing most disorders is actually damaging the surrounding supporting cells of the central nervous system rather than the neurons themselves.  

Supporting cells include glial cells, microglia, astrocytes, and others. Microglia cells are especially active in neuroinflammation. Like most cells and systems in the human body, balance is necessary for the proper function of the microglia. Too little activation results in less recovery of injury in the CNS, and too much activation can induce autoimmune responses and neural death. Glia represent the link between chronic pain and neuroinflammation.

Read more here to learn how PEA affects inflammation.


Neuropathic pain is almost untreatable and results in chronic pain. This is from damage, degeneration, or dysfunction in the sensory system. Neuropathic pain is considered with spinal cord injury, diabetes, multiple sclerosis, stroke, cancer, and other metabolic problems. Neuropathic pain is dependent on supporting structures of the central nervous system (CNS) and peripheral nervous system (PNS).  

Microglia are activated in the face of injury or infection in order to bring immune cells to the CNS and PNS. This allows the immune system to fight off the infection, remove damaged cells, clean up reactive oxygen species.

However, persistently active microglial cells will eventually cause cognitive issues and chronic pain through pathological functions.

To make a long explanation shorter – microglial cells lead to peripheral and central sensitization and inflammatory and neuropathic pain because of the over-release of TNF-alpha and IL-1Beta. These neuromodulators are produced after injury or infection of peripheral and central nerves. This means that chronic pain is actually a result of imbalance in the immune system.

The immune system is activated to aid the nervous system when the microglial cells ask for help. The microglial cells are always surveying at the cellular level. When pathogens or injury are discovered, cytokines are released that call in the immune cells to clean up and fight off the pathogenic insult. This promotes an inflammatory response which creates neurotoxins. The neurotoxins in turn induce more inflammation. Without a good system to control the toxins produced during the treatment of the pathogen or injury to the nervous system, neuroinflammation will occur.  


There are many pharmaceutical companies striving to make mass-produced synthetic drugs to treat this source of chronic pain, neural inflammation, and other disorders. However, there are natural substances already available that have been safely used for years that are also available.   

If you believe in empowering patients to treat themselves, as I do, then you must give them the tools to build up their internal systems that protect against neuroinflammation. Lipid mediators have shown to have the ability to protect against neuroinflammation. The level and actions of these important natural lipid molecules are lower in chronic inflammatory states (such as chronic pain).

Among these amazing and natural lipid mediators are the N-acetylethanolamines (NAE). These are natural compounds made on-demand in our bodies at the lipid bilayer of cells. They are made of a fatty acid and an organic ethanolamine compound.  

The reason that cannabidiol (CBD) and medical marijuana work is not because they themselves perform the actions that reduce the symptoms of inflammatory disorders. Rather, CBD simply increases the amount of available anandamide, one of these NAEs. Another very important and very active NAE is palmitoylethanolamide, or PEA.  

PEA protects the nervous system and can control chronic pain. PEA is an endogenous molecule that maintains balance within the cells during neurodegenerative and inflammatory conditions. PEA is a natural way to counterattack neuroinflammation, pain, and neuronal damage.  

PEA beneficially modifies the activities of the microglial cells during the pathogenic attacks on the CNS or PNS. This is just one of the proposed mechanisms of action of this normal, naturally occurring fatty acid compound.  


Our essential PEA multivitamin and pain-relieving foot cream from Well Theory have been purposefully-crafted by Dr. Meredith Warner to relieve pain naturally, effectively, and quickly. The ingredients combined within these products work together to regulate homeostasis, reduce inflammation, and support stronger, healthier muscles.

We include these ingredients in our Advanced Connective Tissue Support Multivitamin, in addition to PEA:

  • Magnesium Oxide & Calcium Citrate - promotes healthy bones, reduces muscle cramps, and boosts nerve signaling
  • Vitamin D3 - strengthens nerve health and helps the body to more readily absorb calcium
  • Vitamin C - supports wound healing, collagen formation, and increase the health of bones, joints, and teeth
  • Zinc Gluconate - improves wound healing and connective tissue formation
  • We include these ingredients in our Foot Pain Relief Cream, in addition to PEA:

    • Lidocaine - relieves nerve pain and muscle soreness quickly when applied topically
    • Menthol - interacts with pain receptors to alleviate sensitivity and cool on contact
    • A Curated Blend of Essential Oils - stimulates physical and nerve-related responses to calm irritation, reduce pain, and lessen inflammation

When paired with PEA, these ingredients offer a powerful solution to pain, tension, and improve overall wellness from the inside out.


Our Well Theory multivitamin and foot cream are formulated with PEA to help you find relief from chronic pain easily. Simply incorporate our daily multivitamin into your routine to introduce pain relief and joint and tissue support, and natural anti-inflammatory properties into your day. Our foot pain relief cream works to help diminish pain at the site of sensitivity. Spread a thin layer over the area you are experiencing pain and work it into the skin to begin feeling its effects!

Pair Well Theory products with The Healing Sole to send foot pain running. These products work both within the body and topically to help you go throughout your day without pain and sensitivity. Our Well Theory products are back in stock, so make sure to order today!


Dr. Meredith Warner is the creator of The Healing Sole and Well Theory. She is a board-certified and fellowship-trained Orthopedic Surgeon and Air Force Veteran.

Dr. Warner has treated countless patients for heel pain and plantar fasciitis pain in her private practice, Warner Orthopedics and Wellness. She developed The Healing Sole so that wearers can harness the body's natural healing power and have an option for everyday relief, without the need for surgery or expensive medical intervention.