Views: 1000 Author: Lin LIU Publish Time: 2025-09-30 Origin: Site
Pain, a crucial survival and protective mechanism of the human body, is a double-edged sword. On one hand, it alerts the body to promptly identify the causes of inflammation and disease, preventing further damage; on the other hand, inflammatory and pain mediators activate pain-sensing nerve receptors, triggering unavoidable pain of varying intensities and escalating inflammatory cascades—ranging from common discomforts like headaches, toothaches, dysmenorrhea, and back pain to severe symptoms such as cramps, spasms, vomiting, and even extreme distress.
A common question arises: "Is medication the only way to relieve pain?" Is there a solution that can both alleviate inflammation and pain while protecting nerves, avoiding the potential liver and kidney damage caused by analgesics?
In fact, the human body has evolved an endogenous anti-inflammatory and analgesic mechanism, centered on a key nutrient for nervous system protection—Palmitoylethanolamide (PEA for short). As a naturally occurring, safe nutrient in the human body, PEA demonstrates significant potential in anti-inflammation, analgesia, and neuroprotection, offering a new direction for health management.
Palmitoylethanolamide (PEA) is a fatty amide compound and an endogenously synthesized biomolecule in the human body, with particularly high concentrations in the brain and central nervous system. Physiologically, PEA acts as the body’s "endogenous repair mechanism" activated in response to stress, pain, and inflammation. When cells suffer damage, PEA synthesis is naturally upregulated, and it exerts anti-inflammatory, analgesic, and neuroprotective effects by regulating homeostasis—this process has been validated in multiple studies [1].
Beyond endogenous synthesis, PEA is also widely present in daily foods, including cheese, egg yolks, meat, milk, peanuts, and soy lecithin. A balanced diet can provide a basic intake of PEA to supplement the body’s needs.
PEA’s anti-inflammatory effects are not mediated by a single pathway but form a multi-dimensional network to inhibit inflammation through regulating cellular metabolism, signaling pathways, and immune responses. The specific mechanisms are as follows:
PEA can specifically bind to and activate Peroxisome Proliferator-Activated Receptor α (PPAR-α)—a nuclear receptor transcription factor that primarily regulates the expression of peroxisome-related genes. Peroxisomes, as key organelles in cells, are involved in core physiological processes such as lipid metabolism, oxidative stress regulation, and cholesterol metabolism. When activated, PPAR-α directly inhibits the activity of the Nuclear Factor κB (NF-κB) signaling pathway, reducing the production of inflammatory factors such as Tumor Necrosis Factor α (TNF-α) and interleukins, thereby blocking the inflammatory cascade at its source.
Mast cells are key effector cells in the immune system, containing various pro-inflammatory mediators (e.g., histamine, interleukins, heparin) in their intracellular granules. Once activated and released, these mediators rapidly trigger local or systemic inflammation. PEA can significantly reduce the number of activated mast cells by regulating cellular signals and inhibit the release of their pro-inflammatory mediators (e.g., histamine, liposomes), thereby reducing the intensity and scope of inflammatory responses.
The Endocannabinoid System (ECS) is one of the core systems maintaining bodily homeostasis, consisting of endocannabinoids (e.g., Anandamide, AEA; 2-Arachidonoylglycerol, 2-AG), cannabinoid receptors (CB1, CB2), and degrading enzymes (e.g., Fatty Acid Amide Hydrolase, FAAH). It plays a vital role in regulating the balance of the nervous, immune, and metabolic systems. PEA can regulate the activity of the ECS through indirect interactions with GPR55 (a novel endocannabinoid receptor) and CB1/CB2 receptors, thereby controlling the production of inflammatory mediators and the function of immune cells, and reducing tissue damage caused by inflammation.
The generation of pain essentially involves a cascade of processes, including the release of inflammatory mediators, activation of neurotransmitters, and excitation of sensory neurons. PEA achieves analgesic effects by specifically targeting key links in this process, with the following specific mechanisms:
Inflammation is the core trigger of pain. By activating PPAR-α to regulate cellular metabolism and oxidative stress, PEA reduces the occurrence of inflammation, thereby eliminating the underlying basis for pain signal generation.
PEA can directly act on the GPR55 receptor (a novel endocannabinoid receptor). By regulating the membrane potential of neurons and the activity of ion channels, it inhibits the excitation of pain-sensing neurons, reducing the generation and transmission of pain signals.
PEA indirectly acts on CB1, CB2 receptors, and Transient Receptor Potential Vanilloid 1 (TRPV1)—TRPV1 is a key cation channel in pain receptors, which can be activated by heat, capsaicin, and inflammatory mediators. By regulating the neural analgesic function of the ECS, PEA blocks the transmission of pain signals to the central nervous system.
PEA can further inhibit mast cells from releasing mediators closely associated with neuroinflammation, such as Nerve Growth Factor (NGF), Cyclooxygenase-2 (COX-2), TNF-α, and Inducible Nitric Oxide Synthase (iNOS). This reduces inflammatory damage to nerve tissue, thereby alleviating neuropathic pain.
According to existing studies [1,2], supplementary PEA shows potential for improving various types of pain, including low back pain, sciatica, osteoarthritic pain, fibromyalgia, carpal tunnel syndrome, peripheral neuropathy, neuropathic pain, toothache, chronic pelvic and vaginal pain, and intestinal inflammatory pain.
PEA’s neuroprotective effects span the entire process of inflammation inhibition, pain relief, and neural repair, with specific manifestations in the following three aspects:
By activating PPAR-α to reduce inflammatory responses, PEA protects nerve cells from attacks by inflammatory factors, maintains the structural integrity and functional stability of nerve cells, and delays the occurrence of neurodegenerative changes.
Persistent pain can lead to overexcitation of nerve cells and subsequent neurological dysfunction. By reducing inflammation, inhibiting neuronal activity, and decreasing the release of pro-inflammatory mediators, PEA alleviates excessive stimulation of nerves by pain, maintaining the normal rhythm of nerve signal transmission.
The endocannabinoid system is involved in the regulation of behavior, emotion, and cognition. Through interactions with cannabinoid receptors, PEA indirectly regulates the activity of this system, thereby adjusting the energy balance of the central nervous system and the metabolism of the peripheral nervous system. This provides support for the generation of neurons (neurogenesis) and the repair and reconstruction of synapses, promoting the recovery and maintenance of neural function.
As an endogenous nutrient that can be synthesized by the human body, PEA has significant natural advantages in anti-inflammation, analgesia, and neuroprotection. Its safety and efficacy have been confirmed by multiple studies [1,2]. Whether for alleviating chronic pain or maintaining nervous system health, PEA provides a safe and effective natural option for human health management, and its application potential in the field of health deserves further exploration.
Important Reminder：All content in this article is for general reference only and is provided solely to offer information support for practitioners in the nutrition and health industry. Descriptions related to efficacy are supported by corresponding data, but they do not represent claims or guidance for consumers. Content related to health, medical care, and technological applications is for reference only. For medical matters, please consult professional medical institutions and follow medical advice. This article does not provide any medical recommendations.
