Unraveling the role of oligodendrocytes and myelin in pain

Oligodendrocytes, the myelin-producing cells in the central nervous system (CNS), are crucial for rapid action potential conduction and neuronal communication. While extensively studied for their roles in neuronal support and axonal insulation, their involvement in pain modulation is an emerging research area. This review explores the interplay between oligodendrocytes, myelination, and pain, focusing on neuropathic pain following peripheral nerve injury, spinal cord injury (SCI), chemotherapy, and HIV infection. Studies indicate that a decrease in oligodendrocytes and increased cytokine production by oligodendroglia in response to injury can induce or exacerbate pain. An increase in endogenous oligodendrocyte precursor cells (OPCs) may be a compensatory response to repair damaged oligodendrocytes. Exogenous OPC transplantation shows promise in alleviating SCI-induced neuropathic pain and enhancing remyelination. Additionally, oligodendrocyte apoptosis in brain regions such as the medial prefrontal cortex is linked to opioid-induced hyperalgesia, highlighting their role in central pain mechanisms. Chemotherapeutic agents disrupt oligodendrocyte differentiation, leading to persistent pain, while HIV-associated neuropathy involves up-regulation of oligodendrocyte lineage cell markers. These findings underscore the multifaceted roles of oligodendrocytes in pain pathways, suggesting that targeting myelination processes could offer new therapeutic strategies for chronic pain management. Further research should elucidate the underlying molecular mechanisms to develop effective pain treatments.image This review includes 12 studies focusing on neuropathic pain resulting from peripheral nerve or spinal cord injuries, chemotherapy, and HIV. The studies indicate that reduced oligodendrocyte numbers and decreased myelin thickness may play a crucial role in the development or maintenance of pain. Additionally, an increase in OPCs could aid in repair, as OPCs expression levels increased in pain, contrary to the decreased expressions of OLs and MBP. Furthermore, two studies showed that exogenous OPCs transplantation has the potential to alleviate pain. Significant gaps still remain in understanding how oligodendrocytes influence pain states, and further research is needed.imageAbbreviations: MBP, Myelin Basic Protein; OLs, Oligodendrocytes; OPCs: Oligodendrocyte Precursor Cells.