Emerging Role of Schwann Cells in Neuropathic Pain: Receptors, Glial Mediators and Myelination

Abstract

Neuropathic pain caused by nerve injury or disease remains a major challenge for modern medicine worldwide. Most of the pathogenic mechanisms underlying neuropathic pain are centered on neuronal mechanisms. Accumulating evidence suggests that non-neuronal cells, especially glial cells, also play active roles in the initiation and resolution of pain. The preponderance of evidence has implicated central nervous system (CNS) glial cells, i.e., microglia and astrocytes, in the control of pain. The role of Schwann cells in neuropathic pain remains poorly understood. Schwann cells, which detect nerve injury and provide the first response, play a critical role in the development and maintenance of neuropathic pain. The cells respond to nerve injury by changing their phenotype, proliferating and interacting with nociceptive neurons by releasing glial mediators (growth factors, cytokines, chemokines, and biologically active small molecules). In addition, receptors expressed in active Schwann cells have the potential to regulate different pain conditions. In this review article, we will provide and discuss emerging evidence by integrating recent advances related to Schwann cells and neuropathic pain.

Mechanical allodynia in mice with tenascin-X deficiency associated with Ehlers-Danlos syndrome

“…4). Notably, disorder of myelin contributes to the development of neuropathic pain 40 . Myelin disorder is associated with expression changes of pain-related molecules including channels, receptors, cytokines, and growth factors, and ephaptic interaction between innocuous Aβ fibers and noxious Aδ and C fibers 41 .…”

Amyloid Proteins and Peripheral Neuropathy

“…A phenomenon that is often observed in familial amyloid neuropathy is defective myelination [ 91 , 307 , 308 ]. As such, impairment in Schwann cell function is emerging as an important mechanism in the development of amyloid neuropathy or neuropathic pain in general [ 309 ]. Schwann cells support the structural and functional integrity of peripheral nerves and are affected by the cellular toxicity of amyloid protein aggregates [ 75 , 90 , 310 ].…”

Schwann Cell Autocrine and Paracrine Regulatory Mechanisms, Mediated by Allopregnanolone and BDNF, Modulate PKCε in Peripheral Sensory Neurons

“…Besides these structural purposes, SCs cross-interact with neurons, specifically with whole axons, regulating their physiological functions. A plethora of mediators is produced and/or released by SCs, thus regulating the neuron-glial interaction, including neuropeptides, cytokines, growth factors, integrins, neuregulins, neurotransmitters and neuroactive steroids [3][4][5][6][7].…”