Nature and mechanism of peripheral nerve damage in an experimental model of non-freezing cold injury.

Non-freezing cold injury (NFCI), so called trench foot, is a condition characterised by a peripheral neuropathy, developing when the extremities are exposed for prolonged periods to wet conditions at temperatures just above freezing. Classically, military personnel are affected, with 14% of casualties in the Falklands conflict afflicted. Clinically, NFCI is characterised by a well-defined acute clinical picture and chronic sequelae. Little is known regarding the pathophysiology and treatment of this condition. Opinions vary as to the type of nerve fibres most susceptible to damage and proposed mechanisms of injury include direct axonal damage, ischaemia and ischaemia/reperfusion. A series of investigations has been performed to clarify which populations of nerve fibres are more susceptible to damage, and to elucidate the exact mechanism of nerve injury. An in vivo rabbit hind limb model, subjected to 16 h of cold immersion (1-2 degrees C), provided the basis of this study. Nerve specimens were examined by semi-thin sectioning for myelin fibre counts, by electron microscopy to assess the unmyelinated fibre population, and fine nerve terminals in plantar skin were assessed immunohistochemically. The results showed that large myelinated fibres were preferentially damaged, while small myelinated and unmyelinated fibres were relatively spared. Nerve damage was found to start proximally and extend distally with time. Serial temperature measurements identified a warm-cold interface in the upper tibial region of immersed limbs. As this was the initial site of injury, this suggested that a dynamic balance exists in the cold immersed limb between the protective effects of cooling and the damaging effects of ischaemia. The non-invasive technique of near infrared spectroscopy was used to measure changes in tissue oxygen supply and utilisation and blood volume. The findings supported the hypothesis that an interface is created at the site of initial nerve damage in the upper tibia, where cyclical ischaemia-reperfusion injury occurs.