Pathophysiology and diagnosis in patients with sympathetically dependent pain

Abstract

Chronic pain in a distal extremity that is accompanied by autonomic dysfunction in the same region is taken to indicate reflex sympathetic dystrophy. Typically, hyperalgesia to light touch is present in addition to the spontaneous pain. The absence of heat hyperalgesia indicates that the underlying mechanism is central rather than peripheral sensitization. This mechanism is similar to that of secondary hyperalgesia in the intact skin surrounding an injury site. Sympathetically maintained pain (SMP) is diagnosed, when these sensory symptoms are reversible under sympathetic blockade. SMP is not due to hyperactivity of sympathetic efferents but to receptor supersensitivity, probably by overexpression of alpha(1)-adrenergic receptors on nociceptive primary afferents. This way normal levels of norepinephrine can cause pathological spontaneous activity of nociceptors which maintains the central sensitization. Chronic burning pain and cutaneous hyperalgesia may also be independent of the sympathetic innervation of the skin. In this case, central sensitization is maintained by other mechanisms. A role of the sympathetic nervous system in the pathogenesis of pain cannot be deduced simply from the simultaneous presence of sensory and autonomic clinical signs and symptoms. Therefore, sympathetic blockade in a patient initially is a diagnostic procedure, aiming to demonstrate the presence of the symptom SMP. Therapeutic blockade is only indicated after this demonstration. For the substantial number of patients with sympathetically independent pain, other treatment modalities are needed which may for example attack central sensitization.