Pain science and mobilisation of painful compressive neuropathies

Abstract

Recent experimental investigation indicates that demyelination of peripheral nerve trunk and spinal nerve root neurones may be responsible for much of the abnormal pathology and, therefore, symptomatology of common peripheral entrapment or compressive neuropathies such as carpal tunnel syndrome. Studies suggest that repetitive relatively low level mechanical stimuli such as shear ('slide'/'glide') and stretch ('tension') mimic the clinical situation, and act directly on Schwann cells. This causes Schwann cells to dedifferentiate (lose special form, function), proliferate (divide) and undergo apoptosis (programmed cell death). As part of the process of stimulus-induced demyelination Schwann cells down-regulate myelin-forming proteins (and up-regulate nonmyelin markers). Downregulation of myelin protein together with upregulation of a growth cone molecule (GAP-43), appear to be involved in the sprouting of unmyelinated afferents seen with compressive neuropathy. In addition, the expression by Schwann cells of a factor that is 'trophic' for unmyelinated afferents, probably contributes to a general increase in the ratio of nociceptors to proprioceptors. Presumably such Schwann cell-mediated change in afferent phenotype facilitates the production of pain. Importantly, at the time these and other pathological events are occurring the usual triggers for cell dedifferentiation, proliferation and apoptosis – namely, axon damage, Wallerian degeneration and macrophage signalling – are absent. Together the evidence supports the proposal that compressive peripheral neuropathy is a mechanically initiated (maintained?) Schwann cell-mediated condition. As such, this proposal is relevant to movement-based therapies that use 'diagnostic' and therapeutic mechanical stimuli in the management of peripheral compressive neuropathies.