ATP spreads inflammation through crosstalk between sensory neurons and interneurons in RA

Neural circuits between lesions play a paramount role in transmission of local inflammation in RA. A recent study published in the Journal of Experimental Medicine has reported that the spreading of inflammatory signal from one side of the joint to the other occurs via ATP-based sensory neuron-interneuron crosstalk.

In the mice model study conducted by a group of researchers from Japan and the USA, led by Professor Masaaki Murakami, evaluated the hypothesis whether the neural crosstalk could be responsible for remote inflammation in RA. The mice models were categorized into control and test groups. The researchers interrupted the sensory neural circuits between the left and right ankle joints in the test group. They subsequently induced arthritis of the left ankle in both sets of mice and investigated the spread of arthritis to the right ankle. The findings showed increased in ATP and the development of inflammation in both the joints, due to the transmission of the inflammation signal in one joint to the other via a sensory neuron connection.

Moreover, surgical ablation or pharmacological inhibition of this neural pathway contributed to the prevention of inflammation transmission from one side to the other. Mechanistic analysis has proven the intermediary role of ATP both as a neurotransmitter and an inflammation enhancer. These findings also highlight the therapeutic value of blockade of remote inflammation gateway reflex in preventing the progression of inflammatory diseases. However, further research is warranted to corroborate the present study findings in humans.

Reference: Hasebe R, Murakami K, Harada M, et al. ATP spreads inflammation to other limbs through crosstalk between sensory neurons and interneurons. J Exp Med. 2022;219(6):e20212019.