Cold injury to nerves is not due to ischaemia alone.

The effect of cold on nerve fibre populations may be quite selective. Thus it was possible in the present study, with precise timing of a non-freezing cold nerve injury, to destroy myelinated fibres, but leave unmyelinated fibres intact. The aetiology of this cold-induced selective peripheral nerve pathology remains controversial, but recent evidence suggests that ischaemia plays an important role. To investigate this matter further, we have sought to determine whether ischaemia alone might account for such discrete nerve pathology, in a series of non-freezing cold injury paradigms. Compared with previous 'pure' ischaemic peripheral nerve models, notable differences were found in the present paradigms (early post-ischaemic luxury perfusion and severe nerve pathology), suggesting a multifactorial aetiology. Nonetheless a tight correlation was evident, with increasing duration of cold injury resulting in a progressively more severe reduction in post-cold nerve blood flow. Given these findings, we would propose that the pathological basis of non-freezing cold nerve injury is one of ischaemia, accelerated and enhanced by direct cold injury.