Chronic pain following partial nerve injury that is associated with objective signs of conduction loss presents few diagnostic difficulties. However, diagnosis of patients who present with diffuse symptoms in their limbs of unknown etiology is often a problem. Recent animal and human experiments suggest that diffuse painful symptoms may be a consequence of relatively minor nerve injuries in which signs of changed nerve function are not initially apparent. This paper reviews the experimental evidence that describes the rather surprising morphological and physiological consequences of such injuries and relates them to human studies on neuropathic pain. These studies demonstrate that pain and changed somatosensory thresholds may occur following relatively minor axonal damage and even nerve sheath inflammation when no axonal damage is present.It is proposed that in many patients with diffuse limb pain there may be a contribution from nerve injury, i.e. a neuropathic component. This has implications for treatment of these conditions. Manual techniques and exercises to relieve compressive effects and restore normal neural dynamics should be effective in the management of these conditions.