In addition to be present in spinal MNs and macrophages, P2X4 expression increases in microglia through the activation of IRF8-IRF5 transcription factors during the symptomatic phase of ALS as commonly observed in neuropathic pain and neurodegenerative diseases associated with inflammation [32, 38, 76]. This evidence concerns the gene P2RX4 and amyotrophic lateral sclerosis.