Neurogenic inflammation is a physiological process where the nervous system directly initiates and modulates inflammatory responses. Unlike inflammation primarily driven by the immune system, it highlights the active role of nerve cells in influencing the body’s reaction to various stimuli. This process results in local inflammatory responses, including redness, swelling, increased temperature, tenderness, and pain.
How Nerves Initiate Inflammation
Nerves initiate inflammation through specific sensory nerve fibers, primarily C-fibers. These fine, unmyelinated C-fibers detect low-intensity mechanical and chemical stimulations. When stimulated by tissue damage or painful stimuli, these nerve endings release local substances, activating an inflammatory response.
A key pathway is the “axon reflex,” where a nerve signal travels backward along a nerve fiber from the site of stimulation. This retrograde signal causes the release of inflammatory chemicals at distant sites along the nerve’s distribution, spreading inflammatory signals and contributing to a broader reaction in surrounding tissues.
Persistent local depolarizations within these nerve fibers result in the rapid, localized release of neural mediators from peripheral axons and their terminals. This direct release of substances from nerve endings distinguishes neurogenic inflammation. For example, electrical stimulation of dorsal roots induces vasodilation in the epidermis, supporting the nervous system’s direct role in inflammatory changes.
Key Chemical Messengers and Receptors
Neurogenic inflammation involves specific neuropeptides released by activated nerves, primarily Substance P and Calcitonin Gene-Related Peptide (CGRP). Substance P causes smooth muscle contraction (e.g., bronchospasm), increases blood vessel permeability leading to fluid leakage, stimulates mucus secretion, and activates inflammatory cells.
CGRP promotes vasodilation (widening of blood vessels). Both Substance P and CGRP activate mast cells, which release histamine and other inflammatory mediators, amplifying the inflammatory response.
Neuropeptide release is often triggered by specific ion channels on nerve endings. The Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Potential Ankyrin 1 (TRPA1) channels detect noxious environmental stimuli. Activation of TRPV1 (the heat/capsaicin receptor) and TRPA1 (the wasabi receptor) on sensory neurons leads to pro-inflammatory neuropeptide release.
TRPA1 channels can also be stimulated by lipopolysaccharides, components of bacterial cell walls, potentially causing acute neurogenic inflammation.
Conditions Linked to Neurogenic Inflammation
Neurogenic inflammation plays a role in various health conditions. In migraine, stimulation of the trigeminal nerve leads to neurogenic inflammation through neuropeptide release. These include Substance P, CGRP, nitric oxide, vasoactive intestinal polypeptide, and neurokinin A, which contribute to the characteristic pain and other migraine symptoms.
Psoriasis, a chronic skin condition, also involves neurogenic inflammation. Activated nerve endings in the skin release mediators, contributing to the redness, scaling, and inflammation of psoriatic plaques. Sensory neurons expressing TRPV1 ion channels are particularly involved, triggering neuropeptide release that stimulates mast cells and perpetuates the inflammatory cycle.
In asthma, neurogenic inflammation contributes to bronchial inflammation and airway hyperresponsiveness. Neuropeptides like Substance P cause airway smooth muscle contraction, leading to bronchospasm. This process, along with increased vascular permeability and mucus secretion, exacerbates respiratory symptoms.
Complex Regional Pain Syndrome (CRPS) is a chronic pain disorder characterized by severe pain, inflammatory symptoms, and abnormalities in sensory, trophic, autonomic, and motor systems. Neurogenic inflammation is a significant factor in CRPS, where nerve injury can lead to persistent inflammation and pain. Patients often experience symptoms like allodynia, thermal and mechanical hyperalgesia, changes in sweating, and abnormal hair and nail growth, influenced by ongoing neurogenic inflammatory processes.