Remak cells are non-myelinating Schwann cells that ensheath bundles of unmyelinated axons in the peripheral nervous system. Named after the German anatomist Robert Remak who first described them in the 1830s, these cells play essential roles in axon maintenance, nerve regeneration, and neuropathic pain. Remak cell dysfunction is implicated in various peripheral neuropathies and chronic pain conditions[1].
Unlike their counterparts that form myelin (myelinating Schwann cells), Remak cells surround multiple small-diameter axons (C-fibers and Aδ-fibers) together within a single Schwann cell groove. This association begins during development when Schwann cells destined to become Remak cells fail to radially sort large-diameter axons, instead maintaining them in bundles[2].
Remak cells express distinct molecular markers including:
They differ from myelinating Schwann cells in their:
Remak cell somata are located along the length of peripheral nerves, typically 10-20 μm in length. The nucleus is elongated, and the cytoplasm contains characteristic intermediate filaments.
Remak cells extend multiple longitudinal processes that create grooves (cervices) for axon bundling. Each Remak cell can ensheath 5-20 unmyelinated axons of varying diameters.
Unlike astrocytes, Remak cells are surrounded by a basal lamina that:
Remak cells provide critical trophic support to unmyelinated axons:
While they do not generate saltatory conduction, Remak cells influence conduction in unmyelinated fibers:
Following nerve injury, Remak cells are crucial for regeneration:
Remak cells are key players in neuropathic pain development:
Several pain therapies target Remak cell function:
Remak cell dysfunction contributes to diabetic peripheral neuropathy:
Chemotherapeutic agents target Remak cells:
Some CMT subtypes involve Remak cells:
Autoimmune attacks can target Remak cells:
The study of Remak Cells has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Jessen KR, Mirsky R. The origin and development of glial cells in peripheral nerves. Nat Rev Neurosci. 2005;6(9):671-682. ↩︎
Feltri ML, Poitelon Y, Previtali SC. How Schwann Cells Sort Axons: New Insights. Neuroscientist. 2016;22(3):252-265. ↩︎
Bhide PG. A quantitative analysis of the morphology of the Schmidt-Lanterman incisures in the mouse. J Anat. 1996;188(Pt 3):695-701. ↩︎
Nave KA, Trapp BD. Axon-glial signaling and the glial support of axon function. Annu Rev Neurosci. 2008;31:535-561. ↩︎
Ren K. Emerging role of satellite glial cells in orofacial pain. J Dent Res. 2019;98(9):1064-1072. ↩︎