02/27/2026
Fibromyalgia is a chronic pain condition that affects millions of people worldwide, and is characterized by widespread pain, fatigue, sleep disturbances, and cognitive difficulties. It involves the nervous system, immune signaling, and biochemical imbalances. Fibromyalgia and the critical roles played by bradykinin, Substance P, and central sensitization in the creation and maintenance of pain will be explored.
Discovering why these pain-amplifying molecules accumulate, and what you can do to support your body’s natural regulatory systems can provide you with insight, and the opportunity to discuss treatment options with your healthcare provider.
What is Fibromyalgia?
Fibromyalgia is a disorder of the nervous system’s pain processing pathways. Unlike pain caused by an injury or tissue damage, in fibromyalgia, pain is amplified due to central sensitization, which is a heightened sensitivity of the nervous system that causes normal sensory signals to be perceived as painful.
Core Symptoms
• Widespread musculoskeletal pain
• Tender points in muscles and joints
• Fatigue and low energy
• Sleep disturbances, including unrefreshing sleep
• Cognitive symptoms (“fibro fog”)
• Heightened sensitivity to touch, light, sound, or temperature
Central Sensitization: The Nervous System on High Alert
Central sensitization occurs when the spinal cord and brain become hyper-responsive to pain signals. In fibromyalgia, this process is amplified by two key peptides, which are short strings of amino acids. These include:
1. Bradykinin which is a small inflammatory peptide that triggers nerve activation and vasodilation
2. Substance P which is a neuropeptide released from sensory nerves that amplifies pain signaling in the spinal cord
Together, these molecules create a feedback loop of pain amplification.
How Bradykinin Contributes to Pain
Bradykinin is normally produced in response to tissue stress or inflammation and broken down rapidly by enzymes such as:
• Angiotensin-converting enzyme (ACE)
• Neprilysin
• Aminopeptidase P
• Neutral endopeptidase
In fibromyalgia, bradykinin accumulates due to:
• Impaired enzyme function caused by oxidative stress and mitochondrial dysfunction
• Chronic neuroinflammation that suppresses enzyme activity
• Reduced blood flow and reduced oxygenation in tissues, triggering overproduction
Excess bradykinin activates pain receptors (B1 and B2) on nerves, increasing Substance P release and promoting neurogenic inflammation.
How Substance P Amplifies Pain
Substance P is a primary neurotransmitter of pain. Elevated levels have been observed in the Cerebrospinal Fluid (CFS) of fibromyalgia patients, and can sometimes be two to three times higher than in healthy individuals.
Its effects include:
• Heightening spinal cord neuron excitability
• Lowering pain thresholds
• Promoting persistent neuroinflammation
• Sustaining central sensitization
When bradykinin triggers its release, the nervous system enters a self-perpetuating cycle, which maintains chronic pain.
Why These Molecules Accumulate
Bradykinin and Substance P accumulation results from a combination of factors.
1. Enzyme Impairment
Oxidative stress and mitochondrial dysfunction reduce ACE and neprilysin, which are enzymes that degrade bradykinin, and slow peptide breakdown.
2. Chronic Neuroinflammation
Activated glial cells within the brain and mast cells from the immune system release cytokines that suppress enzyme function.
3. Reduced Circulation and Oxygen
Microvascular dysfunction stimulates bradykinin production.
4. Positive Feedback Loop
Elevated bradykinin → more Substance P → more neuroinflammation → further enzyme impairment → continued peptide accumulation.
This combination explains why fibromyalgia pain is persistent and amplified even in the absence of tissue damage.
Triggers and Contributing Factors
• Stress and trauma (emotional, or physical such as a fall or car accident)
• Infection or immune activation
• Hormonal imbalances
• Toxin exposure including environmental chemicals
• Nutritional deficiencies that affect enzyme function, especially zinc, magnesium, and antioxidants
Treatment Approaches
The most effective ways to restore bradykinin and Substance P regulation involve improving the body’s own enzyme function by:
• Reducing oxidative stress
• Improving mitochondrial function
• Improving endothelial health
• Restoring nervous system regulation
• Improving sleep quality
• Reducing chronic inflammation
Proteolytic enzymes help your body to break down proteins. These include serrapeptase, bromelain, and nattokinase, which can help break down pro-inflammatory peptides including bradykinin and Substance P. This can help to reduce nerve sensitization, and support relief from both inflammation and chronic pain. These enzymes work by breaking peptide bonds, and effectively decrease the levels of these signaling molecules that contribute to central and peripheral sensitization.
Typical adult dosages vary by the type of proteolytic enzyme. For serrapeptase, common ranges are 10,000–60,000 IU per day, often divided into two or three doses on an empty stomach to maximize absorption and prevent interference with food proteins. Bromelain is generally taken at 250–500 mg per day on an empty stomach, while nattokinase is often dosed at 100–200 mg daily, also taken away from meals. Taking proteolytic enzymes between meals ensures that they enter the bloodstream directly rather than being used for digesting food, optimizing their systemic anti-inflammatory and peptide-modulating effects.
DISCLAIMER : This is intended as general information, and is not medical advice. Always speak with your healthcare provider prior to taking any supplements to ensure that they are appropriate and safe for you medically.
1. How Diet Affects Bradykinin and Substance P
Both bradykinin and Substance P are regulated by enzymes, and are influenced by inflammation, oxidative stress, and mitochondrial function. Diet can affect all of these pathways by:
A. Reducing systemic inflammation
• Chronic inflammation promotes release and persistence of bradykinin and Substance P.
• Anti-inflammatory foods lower pro-inflammatory cytokines which reduce neuroimmune activation.
B. Supporting antioxidant defenses
• Oxidative stress damages peptide-degrading enzymes such as ACE and neprilysin.
• Foods that contain rich sources of antioxidants such as bell peppers, blueberries, citrus fruits, cocoa, green tea, kale, nuts, raspberries, seeds, strawberries, and turmeric protect these enzymes and mitochondria.
C. Supporting mitochondrial function
• Proper enzyme production and peptide breakdown require healthy mitochondria.
• Nutrient-rich, anti-inflammatory diets supply B-complex vitamins, Coenzyme Q10, magnesium, and other cofactors such as alpha-lipoic acid and L-carnitine.
2. Which foods may be particularly helpful
• Omega-3 rich foods: salmon, mackerel, flaxseed, and chia seeds
• Colourful fruits & vegetables: berries, blueberries, cruciferous vegetables, and leafy greens
• Spices with anti-inflammatory properties: turmeric, ginger, and cinnamon
• Polyphenol-rich foods: green tea, dark chocolate, and olive oil
• Fermented foods: yogurt, kefir, and kimchi to support the gut microbiome and enzyme production
3. Foods to avoid
Some foods may increase inflammation or impair peptide breakdown:
• Processed foods, refined sugars, added starches, trans fats, and inflammatory seed oils
• Alcohol
• Artificial additives such as artificial colour, artificial flavour, and preservatives
• Large amounts of natural ACE-inhibiting foods (e.g., excessive fermented dairy or olive leaf) may hypothetically slow bradykinin breakdown. However, when eaten in moderation, this effect is usually minimal.
4. Realistic expectations
• An anti-inflammatory diet supports the body’s natural peptide regulation, reducing excessive bradykinin and Substance P signaling.
• Benefits from eating an anti-inflammatory diet don’t occur overnight, but over time improvements can occur, especially when combined with other interventions such as:
o Stress management
o Adequate sleep
o Gentle daily exercise such as walking
o Targeted medical therapies
Bottom line
An anti-inflammatory diet creates a biochemical environment that favours the breakdown and regulation of bradykinin and Substance P, thereby helping to reduce nerve sensitization and central sensitization over time. It is an essential tool in reducing fibromyalgia symptoms such as chronic pain, brain fog, fatigue, allodynia, and Raynaud’s.
Medications
• Gabapentinoids (Gabapentin, Pregabalin) can reduce nerve excitability
• Serotonin-Norepinephrine reuptake inhibitors (SNRIs) regulate central pain pathways
• Low-dose Naltrexone modulates neuroinflammation
Nutrition and Lifestyle Support
• Anti-inflammatory diet rich in antioxidants
• Adequate sleep and sleep hygiene
• Gentle exercise
• Stress management and mindfulness
• Eating foods that are rich sources of nutrients that support enzyme function and mitochondrial health including zinc, magnesium, Coenzyme Q10, B vitamins and Vitamin C
Emerging and Adjunct Therapies
• Red light and near-infrared therapy may help to reduce neuroinflammation
• Targeted proteolytic enzymes under your healthcare provider's guidance to support peptide regulation
• Gut microbiome restoration to improve enzyme production and reduce inflammation
Comfort Measures
• Gentle stretching
• Warm baths and hydrotherapy
• Acupuncture and massage including lymphatic drainage massage
• Cooling or heating pads to relieve tender points
• Pacing activity to avoid overexertion
Key Takeaways
1. Fibromyalgia is primarily a disorder of central sensitization and chronic pain amplification.
2. Bradykinin and Substance P are critical mediators that sustain heightened pain sensitivity.
3. Accumulation occurs due to impaired peptide breakdown, neuroinflammation, mitochondrial dysfunction, and oxidative stress.
4. Treatments focus on regulating the nervous system, reducing inflammation, and supporting natural enzymatic pathways.
5. Lifestyle, diet, and targeted therapies can complement medications to restore balance and improve quality of life.
Fibromyalgia is a complex condition. However, understanding the biochemical and neurological mechanisms behind chronic pain provides hope. With adequate support, you can reduce the chronic pain, fatigue, brain fog, and allodynia associated with fibromyalgia. Over time, it’s possible to improve your ability to function, and regain your quality of life. There is hope for better tomorrows!
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