[Development and therapy of the pain syndrome of reflex sympathetic dystrophy. Clinical expression, experimental investigations, and new pathophysiological considerations.].

Reflex sympathetic dystrophy (RSD) is a disease of the extremities that can be elicited by different factors, occurring at different sites (e.g., trauma, herpes zoster, myocardial infarction). Independently of its etiology, however, the clinical symptoms of RSD are found most often in distal parts of the extremities affected (hand or foot). In a generalized distribution pattern, the following signs, representing a triad of autonomic, motoric and sensory disturbances, are commonly observed in these regions: 1. dysregulation of blood flow to the skin and of sweating, together with diffuse swelling, 2. impairment of movement and muscular strength; 3. diffuse sensory skin disturbances and spontaneous pain of ariable character (e.g., burning, throbbing, aching, shooting). Pain sensation is generally diffuse; in most cases it is deep and less often, superficial (probably representing bone or skin pain, respectively). This triad occurs at the very onset of RSD. If the distribution pattern is generalized, it can be used as a diagnostic criterion for RSD. Our experimental results support the idea of disturbances of skin blood flow related to abnormal vasoconstrictor outflow. This assumption is primarily based on two observations: 1. 73% of 97 RSD patients (upper extremity affected) showed systematic side differences in fingertip temperatures at room temperature. All points measured on the affected side had higher (n=51) or lower (n= 20) temperature values than corresponding sites on the healthy extremity. Such systematic side differences were found only in 16% out of 79 healthy subjects (p</=0.0001). 2. Whole-body cooling, hands excluded, induced abnormal changes in skin blood flow of the hands affected (e.g., faster or slower decrease in blood flow on the affected side compared to the healthy extremity). This generally leads to higher mean side differences in skin temperature during the whole cooling period in 38 RSD patients as compared with 18 healthy subjects (2.5 degrees vs 0.9 degrees C,p</=0.001). Such abnormalities of skin blood flow were found in the whole distal extremity, independent of the factor eliciting RSD (e.g. proximal or distal trauma, partial nerve lesion). In most cases the predominant symptoms of RSD are swelling of a distal extremity and spontaneous pain. It is presumed that these symptoms are primarily initiated by a noxious event, which can be recognized as a common factor in the history of the disease preceding RSD in most cases. Nociceptor impulses during this event may induce disturbances of sympathetic vasoconstrictor outflow via reflex mechanisms. Most relevant to these symptoms is the hypothesized imbalance between activity (tone) of vasoconstrictor neurons supplying arteries (AVT) and those supplying veins (VVT). If VVT becomes higher than AVT, venous return is impaired, capillary pressure increases, and edema results. Disturbed micromilieu and increased local pressure lead finally to excitation of nociceptors in the tissues affected (e.g., skin and bones). This excitation, in turn, maintains the abnormal vasoconstrictor outflow via reflex mechanisms, thus initiating a vicious circle. Sympatholytic therapy can interrupt the abnormal vasoconstrictor outflow, leading to increased venous return and reducing interstitial pressure and nociceptor activation (interruption of the vicious circle). If sympatholytic therapy is applied early, full recovery may occur.