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Inflammatory Arthritis Spread by ATP and Neural Crosstalk

May 19, 2022 4:50 pm

A novel study from the Journal of Experimental Medicine suggests that a reflex neural signaling at sites of inflammation may lead to spread to other inflammatory sites via and ATP-mediated neural crosstalk. Such findings may be important in disorders like rheumatoid arthritis (RA) and may lead to future novel interventions for RA.

The goal was to assess whether specific neural signaling leads to vascular and immune promotion of local and remote inflammation. Investigators used murine models of RA. They induced ankle arthritis and then observed spread of arthritis to the contralateral ankle.  Established inflammation was amplifed by IL-6 in the affected joint, that causesd ATP secretion that signals through the spinal cord, which in turn, triggers an increase in ATP concentrations and inflammation in the unaffected joint.

With surgical ablation or pharmacological inhibition (to disrupt sensory neural circuits) of this neural pathway they were able to prevent inflammation development on the other side.  They showed that this neural crosstalk was mediated by ATP, serving as a neurotransmitter and an inflammation enhancer.

The authors stated that this "remote inflammation gateway reflex", may have therapeutic value for inflammatory diseases, especially RA, where the  hallmark finding is "symmetric polyarthritis". 

These data suggest that sensory neuronal crosstalk, mediated by ATP, may account for the symmetry of RA. 

Disclosures
The author has no conflicts of interest to disclose related to this subject

Rheumatologists’ Comments

David S Knapp

| May 22, 2022 4:06 pm

This observation is not new as previous reports in the 50's, 60's and 70's discuss either unilateral resolution or prevention of inflammatory arthritis and even scleroderma before or after neurologic events that were unilateral in nature. A connection between the immune system and nervous system has long been suspected based on such clinical events as well as observed anatomical innervation of inflamed synovial tissues. Other organ systems (nervous, endocrine, special senses, gut, etc.) may also be affected by the neuroimmune system in regards to an etiology. Denervation interventions in animal models of inflammatory arthritis suggest an intact nervous system may play a role in what was once called "neurogenic" inflammation.

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