Approximately 15-20% of adults have a food intolerances or sensitivity.1 These patients report a
wide range of symptoms, including gastrointestinal distress including abdominal pain,
gas/belching/burping, IBS, Crohn’s, ulcerative colitis, peptic ulcer, migraines, chronic fatigue,
arthritis, rashes, respiratory distress, skin issues, weight gain, increased illnesses/immune
imbalances, and chronic pain issues.1
.3
.6,7
Current literature supports the fact that food allergies, intolerances and sensitivities are directly
tied to metainflammatory sequelae and the release of GUT mucosal IgE and IgG type
antibodies.2,3,4 This inflammatory signaling “drives” pain perception. How you deal with this
metaflammation dictates patients health outcomes and their ability to overcome pain.
One of the main culprits of metainflammatory signaling is the GUT, including mucosal integrity
and microbiome issues.5 As we know, food allergies/sensitivities and intolerances are closely
related to GUT health integrity.
Background
Globally, it is estimated that 1 in 5 individuals suffer from chronic pain, with prevalence increasing
with age, nutrient status, and stress level.
6 The pathophysiology of chronic pain encompasses
multifaceted sensory, immune, and inflammatory signaling interactions within both the central and
peripheral nervous systems. Microglia, the resident macrophages of the central nervous system
(CNS), are critically involved in the initiation and persistence of chronic pain.
Briefly, under steady-state conditions, microglia serve as the sole immune cells of the central
nervous system (CNS). As macrophages, these myeloid cells
have been implicated in a wide array of CNS processes such as
mediating inflammation, directly combating infection, and
clearing cellular debris via phagocytosis.7 While some features
of closely regulated pro-inflammatory activity are necessary for
healthy neurodevelopment, unrestrained early-life inflammation
may alter programming of the microglial population itself,
leading for a lower baseline required for reactivation, thereby
perpetuating inflammatory damage to the neuronal compartment later in life.
8
Microglia respond to local signals from the CNS but are also modulated by signals from the
gastrointestinal tract. Emerging data from preclinical and clinical studies suggest that
communication between the gut microbiome, the community of bacteria residing within the gut,
and microglia is involved in producing chronic pain.9,10,11 Targeted strategies that manipulate or
restore the gut microbiome have been reported to reduce microglial activation and alleviate
symptoms associated with inflammation.12 This data indicates that concern for the gut
microbiome in chronic pain patients is a high impact choice that improves pain outcomes and
overall quality of life.
The microbiome is linked to the CNS via different proposed communication pathways:13
- Bacterial metabolic products including tryptophan metabolites and short chain fatty acids
(SCFA) - Innervation of the gut by the vagus nerve
- Microbe-associated molecular patterns (MAMPs) that drive inflammation
The mechanism by which bacterial products or MAMPs trigger an inflammatory response in the
brain may include entry to the circumventricular organs, areas in the brain where the BBB is less
tightly regulated as in leaky gut syndrome.14
Recent evidence suggests that gut microbiota may also
play a critical role in many other types of chronic pain,
including inflammatory pain, headache, neuropathic
pain, and opioid tolerance. Patients with various pain
“conditions”, including visceral pain, chronic pelvic
pain, fibromyalgia, and osteoarthritis-related knee pain
all display changes in microbiome diversity and
abundance compared to healthy individuals.
15,16
Restoring the gut microbiome following dysbiosis
improves pain responses in animal studies of visceral,
inflammatory and neuropathic pain.17
Gut Microbes and microglia influence chronic pain
by:18
- Vagal nerve signaling
- GUT permeability issues
- Signaling mechanisms – TLR-4-mediated, cytokines, BDNF
Communication between gut microbes and the CNS is mediated by a combination of immune,
enteric, and neural pathways that provide physical and chemical connections between the CNS
and the periphery, and several experimental paradigms have been used to demonstrate that gut
microbes influence many facets of CNS physiology.19
The GUT microbiome is reportedly involved in several types of pain:
- Visceral pain – dyshomeostasis of GUT microbiota; internal pain
generally caused by IBDs including IBS, Crohn’s, ulcerative colitis,
dyspepsia, abdominal pain syndrome, infantile colic and interstitial
cystitis, antibiotic use20,21 - Inflammatory pain – i.e., arthritic pain22
- Neuropathic pain – caused by damage from nerve trauma,
chemotherapy, nutrient deficiencies, cancer, diabetes23 - Headache – studies report direct relationship of migraine headaches to
GI disorders24 - Opioid tolerance – recent studies report long-term use of opioids is
associated with microbial dysbiosis in humans25; long-term use of
morphine can lead to disruption of the intestinal epithelial barrier and
cause leaky gut and also cause enhanced bacterial translocation,
leading to chronic inflammatory upregulation and immune disorders
26
Sympathetic pain
GUT microbiome disruption can also lead to sympathetic dominance, which is reported to lead
to many adverse health effects including PAIN as well.
In some chronic pain states, activity in sympathetic efferent neurons can exacerbate the pain and
sympathectomies relieve it- these patients are said to have
sympathetically maintained pain (SMP).27 An example is
fibromyalgia (FM) – fibromyalgia is a syndrome
characterized by chronic musculoskeletal pain,
hyperalgesia on specific areas of tenderness (tender points)
and by an autonomic nervous system dysfunction
consistent with sympathetic overactivity.28
GUT microbiota individualized diversity is critical to keep the inflammatory cytokines released
by an inflamed GUT from leading to sympathetic nervous system dominance.29
Opioids
The last decade has exposed the harsh realities of using opioids for pain control – it is not a great
idea to use them. Besides the tolerance and dependency, opioids also lead to GUT dysbiosis which
can initiate a host of debilitating and deteriorating chronic health conditions – metainflammation,
type 2 diabetes, cardiovascular issues, sex and thyroid hormone dysregulation, immune issues,
mood disorders, and yes even chronic pain.
30 In conjunction with the issues of addiction and
dependency, opioids are reported to:31
- Modulate intestinal function
- Impair GUT Epithelial Integrity
- Lead to GUT microbial dysbiosis and bile dysregulation – alters xenobiotic metabolism
- Modulate immunity – Th1/Th2 imbalances
- Deplete Melatonin, DHEA and testosterone
Conclusion
Testing for IgE, IgG, IgG4 and complement vs. a food panel is very important for clinicians with
patients experiencing PAIN. Certain foods may trigger GUT microbiome issues that then disrupt
GUT-Brain signaling, thereby leading to increased pain issues.
Also, recommending a diet that minimizes foods that provoke these responses will decrease many
types of inflammation and symptoms and is foundational to wellness. When we are recommending
eating a personalized anti-inflammatory diet, we are optimizing patient’s chance for success and
improved health and vitality. Remember that HPA axis dysregulation due to chronic stress and
imbalanced cortisol levels is directly related to GUT issues, so take that into consideration when
issuing a treatment plan. Proper diet, stress control and sleeping 7-8 hours a night results in stronger
immunity and better protection for the body from many factors including foods that irritate the
GUT and lead to increasing levels of inflammation and pain.
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allergy to food. Curr Opin Allergy Clin Immunol. 2010;10(4):394-9. 4 Berlin MC. Mucosal antibodies in the regulation of tolerance and allergy to foods. Semin Immunopathol.
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Copyright 2021 James LaValle
