Research strategies for pain in lumbar radiculopathy focusing on acid-sensing ion channels and their toxins

In lumbar radiculopathy, the dorsal root or dorsal root ganglia (DRG) are compressed or affected by herniated discs or degenerative spinal canal stenosis. The disease is multi-factorial and involves almost all types of pain, such as ischemic, inflammatory, mechanical, and neuropathic pain. Acid-sensing ion channels (ASICs) activated by extracellular acidosis play an important role in pain generation, and the effects of ASICs are widespread in lumbar radiculopathy. ASICs may be involved in the disc degeneration process, which results in disc herniation and, therefore, the compression of the dorsal roots or DRG. ASIC3 is involved in inflammatory pain and ischemic pain, and, likely, mechanical pain. ASIC1a and ASIC3 may have an important effect on control of the vascular tone of the radicular artery. In the central nervous system, ASIC1a modulates the central sensitization of the spinal dorsal horn. Thus, toxins targeting ASICs, because of their specificity, may help elucidate the roles of ASICs in lumbar radiculopathy and could be developed as novel analgesic agents.