Acid-Sensing Ion Channels in Spinal Disorders: Bridging Disc Degeneration, Radiculopathy, Chronic Pain, and Neural Injury

Acid-sensing ion channels (ASICs) couple extracellular acidification to excitability, inflammation, degeneration, and neural injury. The spine is particularly relevant because the intervertebral disc is physiologically hypoxic and mildly acidic, whereas degeneration, impaired diffusion, mechanical stress, inflammation, ischemia, lactate accumulation, nerve-root compression, and spinal cord injury can further alter local pH. Building on prior ASIC, pain, disc-degeneration, and radiculopathy reviews, we develop a clinically integrated disc–dorsal root ganglion (DRG)–spinal cord proton-sensing axis. Evidence supports context-dependent roles for ASIC1a and ASIC3: disc-cell signaling can affect matrix metabolism, inflammation, stress, apoptosis, and pyroptosis; ASIC3 may also support adaptation to the native acidic disc niche and contributes to peripheral sensory/DRG proton sensing; ASIC1a can amplify dorsal-horn nociceptive signaling and, during severe acidosis, participate in secondary neural injury. Direct clinical evidence, validated biomarkers, and established ASIC-directed therapies remain lacking. We therefore propose the acid-sensitive spinal phenotype as a testable research construct and outline priorities for human phenotyping, spatial and single-cell mapping, tissue pH/metabolite measurement, mechanism-based stratification, selective pharmacology, and translational trials.