One criterion for the diagnosis and a fundamental characteristic of rheumatoid arthritis (RA) is symmetric inflammation, which results in wide spread and severe malformation and immobility in bilateral joints. Furthermore, symmetric clinical symptoms are observed in various inflammatory diseases including psoriasis, pulmonary fibrosis, glomerulonephritis, and sympathetic ophthalmitis. Several studies have suggested that a neurological mechanism is involved in the symmetric symptoms, however, the detailed molecular mechanism to link inflammatory and neurological pathways has not been demonstrated yet. Here, we show using cytokine-induced arthritis, a mouse model of RA that the symmetrical inflammation in ankle joints is developed by the interactions via sensory-interneurons at the lower thoracic cords. Symmetrical ankle joint inflammation was significantly improved by surgical ablation or pharmacological inhibition of this neural pathway. We identified ATP as a key molecule to induce the symmetric inflammation and to activate the neural pathway. Thus, blockades of this regional neural pathway by suppressing ATP or attenuating the excessive activation of sensory-interneuron crosstalk may have therapeutic value for inflammatory diseases, particularly those with symmetric symptoms.