[H1] How inflammation in the body is related to/affects peripheral neuropathy

 

Inflammation and peripheral neuropathies are interlinked with one another because one may determine the intensity of the other. They are part of multiple inflammatory conditions that are responsible for inducing or aggravating peripheral neuropathies.

 

Inflammatory neuropathies is the term used for peripheral neuropathy conditions caused by inflammation. They may either occur due to autoimmune disease or infection in the human body. The primary clinical course depends on the damage of the nervous system due to inflammatory conditions.

 

Before studying their relationships in depth, it is important to know more about them and their working principle individually.

 

[H2] INFLAMMATION

Inflammation is the body’s immune response towards an infection or irritant that might affect a person’s normal health. The biological response is stimulated to fight against any toxic compound or deadly pathogen that might have entered the body. It is divided into two broad types that are acute and chronic.

 

Acute inflammation is a short-term process occurring within minutes or hours, whereas chronic inflammation is a long-term process that lasts for months to years. The process of inflammation is somewhat necessary for good prospective healing, but in the case of chronic inflammation, it leads to deterioration of health.

 

The five main cardinal signs of inflammation are

• Rubor – redness
• Tumor – swelling
• Dolor – pain
• Calor – heat
• Function laesa- loss of function

However, not all five symptoms need to be present to classify inflammation, and sometimes the process is symptomless.

The inflammation symptoms are determined by the events occurring at the microvascular level. These are categorized as the increase in leukocyte count, changes in vascular channels’ permeability, and release of inflammatory mediators.

The basic mechanism of inflammation is regulated by a chain of intracellular and extracellular factors that stimulate and intensify the process. Thismechanism evolves as a trigger, or a foreign body is detected by the receptors present on the cells’ surface. The inflammatory pathway is activated, and markers are released, which further recruit inflammatory cells. These cells then accumulate around the injured or inflamed area. Some of the common inflammatory pathways include JAK-STAT, NF-kB, and MAPK.

[H2] PERIPHERAL NEUROPATHY

The peripheral nervous system comprises the neuronal network that is responsible for sending signals between the central nervous system and the rest of the body. It consists of neurons present outside the brain and spinal cord. These nerves control the body’s healthy functioning by maintaining movements, sensory reception, body coordination, and activities like breathing and heartbeat.

 

Neuropathy is a broader term that includes the destruction of nerves. These damaged nerves, in turn, disrupt the transmission of nerve signals across them. Neuropathy is divided into two main types:

Mono-neuropathy – damage occurs in one nerve.

Polyneuropathy – damage of more than one nerve.

 

Peripheral neuropathy is the medical term that defines the destruction of the peripheral nervous system. This is a disabling condition that might be fatal too. According to studies, at least 2400 people per 100,000 population suffer from peripheral neuropathy. Its risk increases with age.

 

The symptoms of peripheral neuropathy include

• Muscle weakness
• Heat intolerance
• Excessive sweating
• Loss of balance
• Neuropathic pain classified as sharp, burning, and throbbing pain
• Tingling or numbness
• Sensory changes
• Muscle twitching
• Loss of muscular movement
• Abnormal heart rate
• Sexual dysfunction
• Changes in urination, bowel habits, and digestion

[H2] INFLAMMATION IS RELATED TO PERIPHERAL NEUROPATHY

Inflammatory neuropathies occur due to chronic inflammation, commonly as a result of infection or autoimmune diseases. The inflammatory cells attack the nervous system, specifically the nerves, which results in peripheral neuropathy.

The disease progresses slowly and gradually, varying in intensity depending on the severity of nerve damage. Inflammation plays a key role in the pathological progression of chronic disease. The disease initiates with the recruitment of leukocytes and advances under innate and adaptive immunity described as the rapid and delayed immune responses, respectively.

The few questions answered down below give an idea of how both the terms are inter-related to one another.

[H3] How inflammation causes peripheral neuropathy?

As inflammation is triggered under a stimulus’s action, leukocytes (white blood cells) infiltrate the peripheral nerve roots or nerves. Consequently, either the swellings at the terminal end of the axon degenerate or the myelin sheath (lipid layer) covering the neurons demyelinates. The antigen-antibody-mediated disease causes a defect in thetransmission of nerve signals between two neuronal cells, ultimately resulting in sensory and motor defects.

 

[H3] Which inflammatory conditions cause peripheral neuropathy?

The causes of inflammatory neuropathies are classified into two divisions as primary and secondary.

Primary causes involve conditions and infections that directly affect the peripheral nervous system, such as

• HIV/ AIDS
• Herpes zoster
• Hepatitis B and C
• Leprosy
• Lyme disease
• Acute inflammatory demyelinating polyneuropathy (Gullian- Barre Syndrome)
• Chronic inflammatory demyelinating polyneuropathy

Secondary causes cover all those inflammatory conditions, which ultimately damage the peripheral neurons. These include

• Diabetic neuropathy
• Celiac disease
• Rheumatoid arthritis
• Polyarteritis nodosa (PAN)
• Amyloidosis

The three major categories of diseases that are classified as peripheral neuropathies caused by inflammation include

[H3] 1. Gullian- Barre Syndrome (GBS)

A perfect example of autoimmune-induced neuropathy is Gullian – Barre Syndrome. The patient complains of weakness, back pain, reduced sensations, and loss of reflexes that occur within less than four weeks.

 

Though the mechanism of GBS is still not fully understood, according to studies, the immune system of the body attacks the person’s peripheral nervous system. For example, the antibodies targeted against bacteria, Campylobacter jejuni, attack the axons of the motor nerves. This gives the classic clinical picture of GBS. The bacteria’s antigen proteins mimic those present in the peripheral nerves. Thus, they are attacked and trigger the inflammatory process, which then damages the nerve cells.

Lipooligosaccharide (LOS) gene forms the ganglioside of nerve cells and is similar to that present on the pathogen surface. The molecular mimicry triggers the cellular and humoral immune response.

 

Gullian-Barre Syndrome, also known as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), showed inflammatory infiltrates in the spinal cord when studied at the microcellular level. Biopsy showed the deposition of T cells, macrophages, lymphocytes, and antigen-antibody complements around the nerves.

 

Serum inflammatory markers like C-reactive protein, neutrophil-lymphocyte ratio, etc., are considered to be beneficial in determining the prognosis of GBS. Albumin levels in an adult patient are helpful as an independent risk factor.

[H3] 2. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Chronic Inflammatory Demyelinating Polyneuropathy is defined as the chronic form of Gullian-Barre Syndrome that advances over eight weeks in a gradual and progressive manner. The relapsing inflammatory disease affects both, motor and sensory neurons of the PNS.

 

Though studies have failed to identify the disease’s pathophysiology as per its similarity with GBS, CIDP is considered an autoimmune disease. It results in the damage of the myelin sheath (covering over the neurons). Myelin proteins P0, P2, and PMP22 are under investigation because of their abundance in the cells. Axonal loss is considered the key factor in the prognosis of CIDP, resulting in the highest rate of disabilities.

 

The clinical course of CIDP is immune-mediated that depends on the role of T-cell, cytokines, macrophages, and anti-myelin antibodies. Cytokines like tumor necrosis factor (TNF) and T helper cell 1 are the dominating inflammatory factors in the disease that might serve as biomarkers.

 

The inflammatory cell profile of 10 cases of CIDP, when studied immunohistochemically, showed infiltration of CD3 T cells, along with the abundance of CD68 macrophages in some. The cerebrospinal fluid (present in the spinal cord of patients) suffering from the disease showed elevated MIP-3beta and IP-10 proteins, which acts as the chemo-attractants, thus recruiting more inflammatory cells spinal roots.

 

Chemokines help the recruitment of leukocytes in the inflamed areas of the peripheral nervous system, and when studied, their receptors like CCR-1, CCR-2, etc., showed positive changes in mononuclear inflammatory cells.

 

[H3] Vasculitic Neuropathy

The inflammation of the blood vessels is called vasculitis, and when this affects the blood vessels supplying the nervous system, it results in vasculitic neuropathy. The disease progress from single to multiple mononeuropathies asymmetrically, resulting in both sensory and motor defects.

 

Peripheral neuropathy is seen in patients with inflammatory vasculitis secondary to conditions like rheumatoid arthritis or diabetes. The prognosis is dependent upon on the size of the blood vessel involved and the intensity of nerve damage that will occur.

 

Vasculitic neuropathy is highly related to inflammation as the diagnosis of the disease directly depends on the level of inflammation around the vessels, dominating over the epineural vessels. This ultimately leads to thrombosis (local clotting within a vessel) and injury due to lack of oxygen.

 

Nerve biopsy categorized the diagnosis with infiltration through the entire wall thickness with; inflammatory cells and necrosis, and loss of myelin sheath. The degree of inflammation depends on the number of inflammatory cells involved to classify vasculitis.

The inflammatory markers that a patient suffering from vasculitis neuropathy is screened for include C-reactive proteins, sedimentation rate, antinuclear antibodies, etc.

 

 

[H2] CONCLUSION

Chronic inflammation, either due to a long-standing or autoimmune disease, starts attacking the human body’s normal healthy cells. When the peripheral nerves are attacked, a person suffers from motor and sensory defects that change his daily life drastically.

This article explains how inflammation and peripheral neuropathy are related and how inflammation ultimately leads to nerve dysfunction. A closer analysis into the mechanism of diseases, helping find the possible treatment or delay the progression towards inflammatory neuropathy.