Neurogenic inflammation
Encyclopedia
Neurogenic inflammation is inflammation
arising from the local release from afferent neurons
of inflammatory
mediators such as Substance P
and Calcitonin Gene-Related Peptide (CGRP)
.
This process appears to play an important role in the pathogenesis
of numerous diseases including psoriasis
, asthma
, fibromyalgia
, eczema
, rosacea
, dystonia
, multiple chemical sensitivity
, and migraine
.
In migraine
, stimulation of the trigeminal nerve
causes neurogenic inflammation via release of neuropeptides including Substance P
, nitric oxide
, vasoactive intestinal polypeptide, 5-HT, Neurokinin A
and CGRP. leading to a "sterile neurogenic inflammation."
blockers show promise. In early trials, the first oral nonpeptide CGRP
antagonist, MK-0974 (Telcagepant
), was shown effective in the treatment of migraine attacks, but elevated liver enzymes in two participants were found. Other therapies and other links in the neurogenic inflammatory pathway for interruption of disease are under study, including migraine
therapies.
Noting that botulinum toxin
has been shown to have an effect on inhibiting neurogenic inflammation, and evidence suggesting the role of neurogenic inflammation in the pathogenesis
of psoriasis
, the University of Minnesota
has begun a clinical trial
to follow up on the observation that patients treated with botulinum toxin for dystonia
had dramatic improvement in psoriasis.
Astelin (Azelastine
) "is indicated for symptomatic treatment of vasomotor rhinitis including rhinorrhea
, nasal congestion, and post nasal drip in adults and children 12 years of age and older."
Statins may be useful for treating diseases presenting with predominant neurogenic inflammation
causes neurogenic inflammation in a rat model. Researchers have theorized that since substance P
which appears at day five of induced magnesium deficiency, is known to stimulate in turn the production of other inflammatory cytokines including IL-1, IL-6, and TNF-alpha, which begin a sharp rise at day 12, substance P is a key in the path from magnesium deficiency to the subsequent cascade of neuro-inflammation. In a later study, researchers observed bone loss in rats that received reduced levels of dietary magnesium, but within the range of dietary intake found in the human population. Even that marginal magnesium deficiency was found to result in an increase in substance P
, TNFalpha, and IL1beta. These and other data support the notion that deficient dietary magnesium
intake, even at levels not uncommon in humans, not only triggers neurogenic inflammation but may also be a risk factor for osteoporosis.
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
arising from the local release from afferent neurons
Sensory neuron
Sensory neurons are typically classified as the neurons responsible for converting external stimuli from the environment into internal stimuli. They are activated by sensory input , and send projections into the central nervous system that convey sensory information to the brain or spinal cord...
of inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
mediators such as Substance P
Substance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
and Calcitonin Gene-Related Peptide (CGRP)
Calcitonin gene-related peptide
Calcitonin gene related peptide is a member of the calcitonin family of peptides, which in humans exists in two forms, α-CGRP and β-CGRP. α-CGRP is a 37-amino acid peptide and is formed from the alternative splicing of the calcitonin/CGRP gene located on chromosome 11...
.
This process appears to play an important role in the pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
of numerous diseases including psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...
, asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...
, eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
, rosacea
Rosacea
Rosacea is a chronic condition characterized by facial erythema . Pimples are sometimes included as part of the definition. Unless it affects the eyes, it is typically a harmless cosmetic condition...
, dystonia
Dystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
, multiple chemical sensitivity
Multiple chemical sensitivity
Multiple chemical sensitivity is a chronic medical condition characterized by symptoms the affected person attributes to exposure to low levels of chemicals. Commonly suspected substances include smoke, pesticides, plastics, synthetic fabrics, scented products, petroleum products and paints...
, and migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
.
In migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
, stimulation of the trigeminal nerve
Trigeminal nerve
The trigeminal nerve contains both sensory and motor fibres. It is responsible for sensation in the face and certain motor functions such as biting, chewing, and swallowing. Sensory information from the face and body is processed by parallel pathways in the central nervous system...
causes neurogenic inflammation via release of neuropeptides including Substance P
Substance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
, nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
, vasoactive intestinal polypeptide, 5-HT, Neurokinin A
Neurokinin A
Neurokinin A is a member of the tachykinin family of neuropeptide neurotransmitters. It is produced from the same preprotachykinin A gene as the neuropeptide substance P. It has various roles in the body of humans and other animals...
and CGRP. leading to a "sterile neurogenic inflammation."
Treatment
The treatment of migraine with CGRPCalcitonin gene-related peptide
Calcitonin gene related peptide is a member of the calcitonin family of peptides, which in humans exists in two forms, α-CGRP and β-CGRP. α-CGRP is a 37-amino acid peptide and is formed from the alternative splicing of the calcitonin/CGRP gene located on chromosome 11...
blockers show promise. In early trials, the first oral nonpeptide CGRP
Calcitonin gene-related peptide
Calcitonin gene related peptide is a member of the calcitonin family of peptides, which in humans exists in two forms, α-CGRP and β-CGRP. α-CGRP is a 37-amino acid peptide and is formed from the alternative splicing of the calcitonin/CGRP gene located on chromosome 11...
antagonist, MK-0974 (Telcagepant
Telcagepant
Telcagepant was an investigational drug for the acute treatment and prevention of migraine, developed by Merck & Co. In the acute treatment of migraine, it was found to have equal potency to rizatriptan and zolmitriptan in two Phase III clinical trials...
), was shown effective in the treatment of migraine attacks, but elevated liver enzymes in two participants were found. Other therapies and other links in the neurogenic inflammatory pathway for interruption of disease are under study, including migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
therapies.
Noting that botulinum toxin
Botulinum toxin
Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals...
has been shown to have an effect on inhibiting neurogenic inflammation, and evidence suggesting the role of neurogenic inflammation in the pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
of psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...
, the University of Minnesota
University of Minnesota
The University of Minnesota, Twin Cities is a public research university located in Minneapolis and St. Paul, Minnesota, United States. It is the oldest and largest part of the University of Minnesota system and has the fourth-largest main campus student body in the United States, with 52,557...
has begun a clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
to follow up on the observation that patients treated with botulinum toxin for dystonia
Dystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
had dramatic improvement in psoriasis.
Astelin (Azelastine
Azelastine
Azelastine is a potent, second-generation, selective, histamine antagonist manufactured by MedaPharma. According to the Allergic Rhinitis and its Impact on Asthma treatment guidelines, intranasal anti-histamines are recommended for the first line therapy of mild intermittent, moderate/severe...
) "is indicated for symptomatic treatment of vasomotor rhinitis including rhinorrhea
Rhinorrhea
Rhinorrhea or rhinorrhoea is a condition where the nasal cavity is filled with a significant amount of mucous fluid. The condition, commonly known as "runny nose", occurs relatively frequently and is not usually considered dangerous. Rhinorrhea is a common symptom of allergies or certain diseases,...
, nasal congestion, and post nasal drip in adults and children 12 years of age and older."
Statins may be useful for treating diseases presenting with predominant neurogenic inflammation
Prevention
Magnesium deficiencyMagnesium deficiency
Magnesium deficiency is a detrimental plant disorder that occurs most often in strongly acidic, light, sandy soils, where magnesium can be easily leached away. Magnesium is an essential macronutrient found from 0.2-0.4% dry matter and is necessary for normal plant growth...
causes neurogenic inflammation in a rat model. Researchers have theorized that since substance P
Substance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
which appears at day five of induced magnesium deficiency, is known to stimulate in turn the production of other inflammatory cytokines including IL-1, IL-6, and TNF-alpha, which begin a sharp rise at day 12, substance P is a key in the path from magnesium deficiency to the subsequent cascade of neuro-inflammation. In a later study, researchers observed bone loss in rats that received reduced levels of dietary magnesium, but within the range of dietary intake found in the human population. Even that marginal magnesium deficiency was found to result in an increase in substance P
Substance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
, TNFalpha, and IL1beta. These and other data support the notion that deficient dietary magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
intake, even at levels not uncommon in humans, not only triggers neurogenic inflammation but may also be a risk factor for osteoporosis.
External links
- Bronchial asthma and other neurogenic diseases: migraine, trigeminal neuralgia and epilepsy
- Schön and Boehncke, Psoriasis: Neurogenic inflammation and other mechanisms NEJM 352:1899-1912, Number 18, 2005