Ross Hauser, MD

Inflammation helps us fight infection and respond to injury. It brings immune cells and chemical messengers to an affected area so the body can remove harmful organisms and damaged tissue. Recovery also requires control: an inflammatory response that persists or becomes excessive can damage otherwise healthy tissue.

The nervous system participates in that control. The vagus nerve is a major communication pathway between the brain and internal organs, and research has identified ways in which vagal signaling influences immune responses. These interactions help explain why nervous-system regulation, intestinal health, and inflammation are often studied together.

At Caring Medical, we are interested in this physiology and in whether cervical structural problems contribute to vagus-nerve dysfunction in selected patients. These are related questions, but they require different evidence. Research showing that vagal circuits can influence inflammation does not establish that cervical instability causes an inflammatory disease.

We examine the inflammatory reflex, its relevance to rheumatoid arthritis, inflammatory bowel disease and type 2 diabetes, and newer findings on the gut–spleen–liver network.

Why inflammation is necessary—and why it must be regulated

Several types of signaling molecules participate in an inflammatory response:

• Cytokines help immune cells communicate. Some promote inflammation, while others limit it or support repair.
• Chemokines help direct immune cells toward sites of infection or injury.
• Reactive oxygen species help immune defenses but can damage proteins, fats, and cells when excessive or poorly controlled.
• Nitric oxide and related molecules influence blood vessels, immune activity, and tissue responses. Their effects depend on the amount produced and the biological setting.

Inflammation can also increase blood-vessel permeability, allowing immune cells and proteins to enter affected tissues. Neutrophils, a type of white blood cell, help defend against infection. Acute-phase proteins such as C-reactive protein, or CRP, can rise during inflammation, and clotting pathways may become involved.

CRP is a marker, not a diagnosis. An elevated result does not identify the source of inflammation or demonstrate vagus-nerve injury. Infection, autoimmune disease, tissue injury, and metabolic illness can all contribute.

Persistent or dysregulated inflammation is important in rheumatoid arthritis, inflammatory bowel disease, and other conditions. Sepsis involves a dangerous, dysregulated response to infection. These conditions have different causes and treatments; they should not be grouped under a single explanation of “low vagal tone.”

What is the inflammatory reflex?

The inflammatory reflex describes neural circuits that sense immune activity and help regulate the response. Sensory signals can communicate information about inflammation to the brain, which in turn influences immune function through autonomic and hormonal pathways.

The cholinergic anti-inflammatory pathway is one part of this system. “Cholinergic” refers to signaling involving acetylcholine, a chemical messenger. Acetylcholine acting on particular receptors on immune cells can reduce production of certain pro-inflammatory cytokines. These effects involve several interacting components rather than a direct command telling every organ to stop inflammation.

A 2025 review examined these neuroimmune mechanisms, including the cholinergic pathway and the hypothalamic–pituitary–adrenal axis, a hormonal system linking the brain with adrenal responses. It discussed findings in cardiovascular, metabolic, respiratory, and gastrointestinal disease. Because the paper combines experimental and clinical research across several conditions, its mechanistic conclusions should not be treated as proof of a universally effective treatment. (1)

What does the spleen have to do with vagal signaling?

The spleen filters blood and contains immune cells that participate in responses to infection and inflammation. It is an important part of neuroimmune research, but the pathway is more complex than the vagus nerve simply releasing acetylcholine directly into the spleen.

Proposed and experimentally studied circuits involve autonomic relays, sympathetic splenic nerves, and immune cells capable of producing acetylcholine. The relative contributions of different routes depend on the experimental model and physiological context. The vagus nerve and sympathetic pathways can participate in interconnected immune regulation. (1)

This existing illustration provides a simplified overview of the cholinergic anti-inflammatory system. It should be read as a diagram of neuroimmune signaling, rather than evidence that every inflammatory condition originates from nerve compression or that inflammation can always be stopped by stimulating the vagus nerve.

Autonomic activity and chronic inflammatory disease

The sympathetic and parasympathetic nervous systems continuously adjust circulation, digestion, and other functions. Their effects vary between organs and circumstances. Parasympathetic activity is not merely the ability to relax, and sympathetic activity is not simply emotional stress.

A 2023 review described associations between chronic inflammatory disease, reduced parasympathetic activity, and increased sympathetic activity. It also discussed findings in which autonomic patterns in rheumatoid arthritis were associated with response to anti-tumor-necrosis-factor treatment. The authors proposed bioelectronic approaches as a potential addition to treatment and emphasized the need for further research. (2)

These observations do not mean that patients have caused their inflammation by failing to relax. Pain, illness, medication, physical conditioning, and immune activity can all affect autonomic measurements. Our discussion of sympathetic dominance provides further background on autonomic symptom patterns.

New 2026 evidence: Vagus-nerve stimulation in rheumatoid arthritis

The strongest clinical evidence comes from trials that test a defined intervention in a defined patient population.

A pivotal randomized, double-blind, sham-controlled trial enrolled 242 patients with rheumatoid arthritis who had an inadequate response or intolerance to biologic or targeted synthetic disease-modifying drugs. An implanted vagus-nerve-targeted system delivered active or sham stimulation for three months. The primary outcome was an ACR20 response, a standard measure requiring improvement in joint findings and other disease measures. (3)

At three months, ACR20 response occurred in 35.2% of the active group and 24.2% of the sham group. The trial met its primary endpoint. Subsequently, all patients received active stimulation, so improvements reported through twelve months came from an open-label period without a continuing sham comparison. Related serious adverse events occurred at a rate of 1.6%; these were perioperative and resolved. (3)

This supports the therapeutic potential of a specific implanted system in selected patients with difficult-to-treat rheumatoid arthritis. It does not establish equivalent benefits from consumer devices, ear stimulation, breathing exercises, or treatment of cervical ligaments. It also does not show that rheumatoid arthritis was caused by cervical instability.

Inflammatory bowel disease and the brain–gut axis

Crohn’s disease and ulcerative colitis are inflammatory bowel diseases, or IBD. They involve intestinal inflammation and can produce abdominal pain, diarrhea, bleeding, fatigue, and other symptoms. They are different from irritable bowel syndrome, although symptoms can overlap.

A 2021 review discussed the inflammatory reflex and brain–gut signaling as potential treatment targets in IBD. It emphasized the continuing need for additional therapies because some patients have persistent disease activity despite available medication. Much of the rationale came from animal models and early human investigations. (4)

A review appearing in a 2026 issue further examined autonomic regulation of intestinal immune responses and emerging bioelectronic approaches. It supports continuing investigation of neural pathways, but a review of mechanisms does not establish which stimulation method reliably improves disease activity in routine practice. (5)

A separate 2026 report followed nine patients from an implanted-stimulation pilot study for four to ten years. Three remained in long-term remission with stimulation alone at ten years, while others required biologic treatment or surgery during follow-up. The small, uncontrolled cohort and changing treatments prevent a reliable estimate of efficacy, but the report supports further investigation of long-term feasibility. (6)

For patients, the useful distinction is between a plausible biological target and a proven intervention. Changes in symptoms or autonomic measurements must be distinguished from objective improvement in intestinal inflammation. Our article on Crohn’s disease and the proposed cervical connection discusses this topic further; the structural hypothesis should remain separate from established gastroenterological diagnosis and care.

The vagus nerve, inflammation, and type 2 diabetes

Type 2 diabetes involves insulin resistance and impaired glucose regulation. Chronic low-grade inflammation can contribute, alongside genetic, metabolic, lifestyle, and other factors.

A 2023 review examined vagal signaling, inflammation, and diabetes. It described associations between lower heart rate variability and diabetes risk, along with emerging evidence that vagal activation may influence glucose-related biomarkers. The authors called for randomized trials to test treatment effects and the proposed anti-inflammatory mechanisms. (7)

Heart rate variability, or HRV, describes variation in the intervals between heartbeats. Certain HRV measures provide information about cardiac autonomic modulation, but they are influenced by breathing, age, medication, fitness, and illness. A low reading does not establish vagus-nerve compression, inability to recover from emotional stress, or the cause of diabetes.

Our explanation of heart rate variability offers additional context. HRV is not a replacement for glucose testing, hemoglobin A1c, or appropriate diabetes care.

The gut–spleen–liver axis: How intestinal health and immune signaling interact

A 2025 review examined communication among the intestine, spleen, and liver in metabolic liver disease. It described a network involving microbial products, metabolic signals, immune cells, blood and lymphatic circulation, and neurological pathways. The spleen was considered an active immune participant rather than simply an organ affected by liver disease. (8)

Gut microbes and the intestinal barrier

The gut microbiome is the community of microorganisms living in the digestive tract. Its products can influence metabolism and immunity. Dysbiosis describes an altered microbial community; it is not a single diagnosis with one agreed treatment.

The intestinal barrier helps regulate what passes from the bowel into the body. When barrier function is impaired, exposure to microbial components and changes in microbial metabolites can affect immune signaling. The review discusses bacterial lipopolysaccharides, bile acids, and short-chain fatty acids. Their effects differ: microbial metabolites are not uniformly harmful, and some support normal intestinal function. (8)

The spleen can influence liver inflammation

Splenic immune cells can produce cytokines and signals associated with fibrosis, the accumulation of scar tissue. The review describes how splenic immune activity may contribute to liver inflammation, scarring, and impaired regeneration in particular disease settings. (8)

Established liver disease can also affect the spleen. Portal hypertension, or increased pressure in the circulation serving the liver, can accompany cirrhosis and contribute to splenic enlargement and hypersplenism. Hypersplenism can involve excessive removal or sequestration of blood cells. These changes belong to a complex liver-disease process and should not be assumed to result from impaired cervical vagus-nerve signaling.

Where the vagus nerve fits

The review identifies vagal and mesenteric immune pathways as possible contributors to communication among these systems. This fits the broader concept that neural, immune, and metabolic regulation interact. The paper is a mechanistic review, not a clinical trial showing that correcting vagal activity reverses liver fibrosis. (8)

It discusses potential approaches involving the microbiome, barrier integrity, and splenic immune function, while calling for further translational research. It does not establish probiotics or prebiotics as a universal liver treatment or support spleen-directed interventions without disease-specific assessment.

For Caring Medical readers, the contribution is a broader understanding of neuroimmune physiology. The review did not test cervical instability or Prolotherapy and cannot establish either a cervical cause of liver disease or an injection treatment for liver inflammation.

Video: Digestion and inflammation—why the whole symptom pattern matters

In this video, Dr. Hauser discusses how digestive complaints can coexist with neck pain, headaches, dizziness, swallowing difficulty, and other symptoms. His explanation reflects our clinical interest in whether a cervical structural problem contributes in selected patients. It also introduces useful questions about digestion and immune regulation. The research in this article helps distinguish established physiology from the proposed cervical mechanism.

Digestive symptoms can occur as part of a broader pattern

At approximately 0:40, Dr. Hauser discusses bloating, constipation, diarrhea, and persistent digestive discomfort. These symptoms may appear alongside neurological or musculoskeletal complaints. Recognizing the combination can help identify questions worth investigating, but coexistence does not prove that all symptoms share one cause.

Inflammatory bowel disease, irritable bowel syndrome, impaired motility, medication effects, and other conditions can produce overlapping complaints. A patient may have more than one condition. The brain–gut and autonomic research supports considering these interactions while preserving the distinctions between diagnoses. (4) (5)

The vagus nerve communicates with the digestive nervous system

Around 0:55–2:25, the video discusses vagal communication, stomach and pancreatic secretions, and intestinal movement. The enteric nervous system is the network of nerves within the digestive tract. It can organize many local functions independently, while signals from the brain and autonomic nerves help modify and coordinate its activity.

This relationship is more complex than the brain telling every intestinal neuron what to do. Changes in neural regulation may influence digestion, but bloating, reflux, or constipation cannot by themselves diagnose vagus-nerve injury or cervical compression. The number of neurons involved does not establish whether a particular person has impaired vagal signaling.

Liver, spleen, and intestinal barrier function

At approximately 3:00–4:30, Dr. Hauser brings together the liver, spleen, fat digestion, inflammation, and intestinal barrier function. These topics provide a useful bridge to the gut–spleen–liver review above. That review describes interactions among microbial products, metabolism, immune cells, and neural pathways; it does not identify cervical instability as the cause of liver disease. (8)

Bile helps the body digest and absorb fats. Its production and release involve several regulatory processes, including hormonal and neural signals, rather than depending solely on vagal input. Likewise, the spleen participates in immune regulation through a network of interacting cells and nerve pathways. Describing it as the single organ that controls inflammation would oversimplify this system. (1)

The discussion of floating stools also needs context: floating alone does not establish fat malabsorption or reveal a cervical cause. Persistent stool changes, particularly with weight loss or other concerning symptoms, warrant assessment. Similarly, food sensitivities or unsuccessful digestive treatment do not by themselves demonstrate impaired intestinal barrier function or a structural neck disorder.

The useful clinical message is to examine the symptom pattern without forcing every complaint into one explanation. The video presents a possible cervical contribution, while the research establishes a broader—and still developing—understanding of communication between the nervous system, digestive tract, and immune system.

Implanted and transcutaneous stimulation are different interventions

Implanted stimulation places a device surgically near a nerve. Transcutaneous stimulation delivers electrical impulses through the skin, often at the ear. These approaches differ in the nerve structures reached, stimulation parameters, treatment duration, and clinical evidence.

This existing illustration shows an ear-based approach. Results from an implanted rheumatoid-arthritis device cannot automatically be applied to this method.

Why stimulation does not always produce an immediate anti-inflammatory response

An important counterexample comes from a controlled study. A randomized, sham-controlled crossover study tested brief ear stimulation in two healthy cohorts: 20 younger participants and 19 older participants. Certain circulating interleukins increased immediately after active stimulation. TNF concentrations did not significantly change. (9)

This does not establish that stimulation worsens chronic inflammatory disease, because the participants were healthy and the intervention was brief. It does show why the phrase “vagus stimulation stops inflammation” is too broad. The measured response depends on the population, protocol, timing, and biological outcome being assessed.

Where cervical instability fits—and what remains unproven

At Caring Medical, we have proposed that cervical dysstructure or ligamentous instability could affect vagus-nerve function in selected patients. Our cervicovagopathy paper presents a hypothesis, retrospective clinic measurements, and a case example. It provides a framework for investigation rather than controlled evidence that cervical treatment prevents or reverses inflammatory disease. (10)

Neck pain, hypermobility, trauma history, or symptoms that change with head position can provide reasons to examine a possible musculoskeletal contribution. These findings do not establish that rheumatoid arthritis, Crohn’s disease, diabetes, or liver disease originates in the neck. The relationship can also operate in the other direction: illness and pain may influence autonomic function.

Prolotherapy is a musculoskeletal injection treatment. Evidence that vagal circuits regulate immunity is not evidence that Prolotherapy treats autoimmune disease, metabolic liver disease, or liver fibrosis. Research on stimulation, research on nerve physiology, and research on ligament treatment must be assessed separately.

Our broader discussion of autonomic nervous system dysfunction and spinal instability explains why overlapping symptoms require careful interpretation and consideration of other diagnoses.

What patients should take from this research

The vagus nerve participates in immune regulation, and selected clinical trials show that targeting neural pathways can produce meaningful effects. Benefits depend on the disease, intervention, and patient population; they are not evidence for one universal anti-inflammatory treatment.

Persistent inflammation or an abnormal CRP needs an explanation based on the clinical picture. Liver abnormalities likewise require assessment for metabolic disease, alcohol-related injury, viral hepatitis, medication effects, autoimmune disease, and other appropriate possibilities. Digestive symptoms alone cannot diagnose liver disease, intestinal permeability changes, or vagus-nerve injury.

Seek prompt medical assessment for jaundice, new abdominal swelling, vomiting blood, black stools, persistent bloody diarrhea, or unexplained weight loss. Confusion in someone with liver disease, severe abdominal pain, or signs of severe infection may require emergency care. These symptoms should not be attributed to a neck problem without evaluation.

The gut–spleen–liver review adds useful physiological context to this article. It expands our understanding of communication among organs while leaving the cervical mechanism and the effectiveness of cervical treatment as separate questions requiring further evidence.

Medical disclaimer: This article is educational and does not replace diagnosis or treatment by a qualified healthcare professional. Do not change prescribed medication or use nerve-stimulation or injection treatment as a substitute for appropriate care of an inflammatory, metabolic, or liver condition.

References

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