Nerve pathophysiology and mechanisms of pain in causalgia

In contrast to sensory endings in skin, muscle, etc., afferents in the mid-course of intact nerves are normally incapable of generating impulses upon slow or prolonged depolarization. However, after various types of nerve injury, including complete nerve section and local demyelination, an ectopic pacemaker capability develops. One peculiarity of such abnormally differentiated sites is chemosensitivity to α-adrenergic agonists and to sympathetic efferent discharge. Such ectopic chemosensitivity may well be involved in the etiology of paraesthesias and pain in reflex sympathetic dystrophies including causalgia. Specifically, it is proposed that the fundamental cause of these conditions is the development of abnormal electrogenic membrane properties in the region of demyelination and sprout outgrowth. These abnormal properties presumably include the appearance of excess inward current conductances and ectopic α-adrenergic receptors. Catecholamines released from sympathetic efferents in the area of injury locally depolarize damaged sensory fibers, and because of the abnormal electrogenic properties of these fibers, an abnormal afferent discharge is generated.