This thesis examined the pathophysiology of entrapment neuropathy, with a focus on carpal tunnel syndrome (CTS). Axonal excitability techniques were utilized to enable studies of axonal membrane function in human subjects in vivo. A further interest of this thesis was to dissect two possible mechanisms that are known to contribute to the pathophysiology of the entrapment neuropathy, namely nerve ischaemia and compression.

During initial studies, the changes in axonal excitability induced by ischaemia were established for healthy individuals, to be used as a template to interpret subsequent studies in the patient groups. These investigations established that refractoriness was the most sensitive excitability measure to identify nerve ischaemia. A contribution from KCNQ2 (a potassium channel proposed to mediate slow nodal K⁺ current, IKs) for generating symptoms resulting from ischaemia such as paraesthesiae, was also suggested.

To better understand the role of ischaemia in the pathophysiology of carpal tunnel syndrome, ischaemia was then applied to CTS patients. These studies reproduced the symptoms of CTS and also established that CTS patients exhibited a greater sensitivity to ischaemia than controls. To explain such a phenomenon it was proposed that axons of CTS patients are delicately poised and relied more heavily on the electrogenic Na⁺/K⁺ pump in the axonal membrane to maintain resting membrane potential.

In a final series of studies, focal nerve compression (FNC) was applied to explore the alternative mechanism which contributes to the pathophysiology of CTS. For theses studies, a custom designed and developed focal nerve compression device was utilized to facilitate the investigation in both CTS patients and control subjects. These studies concluded that mechanisms similar to generalised ischaemia were at work during focal nerve compression. Results from these studies again suggested that axonal function in CTS patients was impaired, with greater reliance on the axonal membrane Na⁺/K⁺ pump