The Hypothesis of Myelinodegeneration as an Initial Risk of Neuropathic Pain

Myelin, which wraps concentrically around axons, is composed of multiple layers of extended plasma membrane produced by myelinating cells, including oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. While extensively studied for roles of myelin in neuronal support and axonal insulation, their involvement in pain modulation is an emerging research area. This review examines the interplay between Schwann cells, myelinodegeneration, and pain, with a specific focus on neuropathic pain resulting from peripheral neuropathies, including diabetic peripheral neuropathy, postherpetic neuralgia, and peripheral nerve injury. Additionally, we summarize evidence implicating oligodendrocytes and myelinodegeneration in central neuropathic pain following spinal cord injury, multiple sclerosis, and stroke. In addition, we discuss potential mechanisms underlying these processes. Finally, we highlight future research directions and underscore the critical role of understanding myelin biology in developing effective treatments for chronic pain, suggesting that targeting myelination processes could offer new therapeutic strategies for chronic pain management.