Translation of symptoms and signs into mechanisms in neuropathic pain.

For centuries, clinicians have been taught to examine and classify patients on the basis of topographical lesion and the underlying pathology. In most clinical specialities, such an approach has been a key element in understanding the pathophysiology of diseases and has led to progress in terms of finding disease modifying or even disease curing therapies. Examples are multiple including bacterial meningitis, painful neuroborrelosis, osteoarthrosis, cancer, rheumatoid arthritis, ischaemic heart disease etc. In most of these disorders, pain can be a major complaint, which then rapidly disappears after the relevant therapy has been given. But what happens when the symptom itself becomes a disease? When pain persists and becomes a chronic problem and when the underlying diseases such as diabetes, cancer, vasculitis are known, or cannot be cured? Are we then helped by the classical ‘Sherlock Holmes’ approach, first, to look for the ‘crime site’ (topography of lesion) and second, for the ‘criminal’ (the disease) that caused this pain? The short answer is: no. Clinical experience and decades of rather discouraging systematic research mainly related to therapy in chronic pain have shown that a strategy directed at examining, classifying and treating pain on basis of anatomy or underlying disease is of limited help to these patients and their pain. These observations have then raised the question whether an entirely different strategy in which pain is analysed on the basis of underlying mechanisms could be an alternative approach to examine and classify patients to obtain a better outcome. Our increasing understanding of mechanisms underlying chronic pain together with the discovery of new molecular targets for modifying pain has strengthened the demand for other ways to treat pain. Woolf and other authors (Woolf et al., 1998; Woolf and Decosterd, 1999; Sindrup and Jensen, 1999) have emphasised the rational for a treatment approach directed at mechanism(s) rather than at diseases because new treatments are being developed on basis of the biological mechanisms that underlie the pain. One area that needs such a new approach is neuropathic pain.