A number of theories have been proposed to explain these regional pain syndromes. For many years they were attributed to a short-circuiting of impulses (ephaptic transmission), the result of an artificial connection between efferent sympathetic and somatic afferent pain fibers at the point of the nerve injury. The demonstration that causalgic pain could be abolished by depletion of neurotransmitters at sympathetic adrenergic endings shifted the presumed site of sympathetic-afferent interaction to the nerve terminals and suggested that the abnormal cross-excitation is chemical rather than electrical in nature. Another possible explanation is that an abnormal adrenergic sensitivity develops in injured nociceptors and that circulating or locally secreted sympathetic neurotransmitters trigger the painful afferent activity. Yet another theory holds that a sustained period of bombardment by sensory pain impulses from one region results in the sensitization of central sensory structures. Causalgia of this type can respond favorably, if only temporarily, to procaine block of the appropriate sympathetic ganglia and, for a longer time, to regional sympathectomy. Prolonged cooling and the intravenous injection of guanethidine, a sympathetic-blocking drug, into the affected limb (with the venous return blocked for several minutes) may alleviate the pain for days or longer. Epidural infusions, particularly of analgesics or ketamine, intravenous infusion of bisphosphonates, and spinal cord stimulators and intrathecal compounds are other forms of treatment, none entirely satisfactorily or for long duration (see Kemler et al). The roles of the central and sympathetic nervous systems in causalgic pain have been critically reviewed by Schott (1986, 2001) and by Schwartzman and McLellan. The reader may be aware of the similarities between these explanations and the ones proposed for all forms of chronic pain, discussed earlier.
Recent investigations have begun to define the molecular changes that occur in sensory neurons and the spinal cord in cases of chronic pain of this type. Alterations in N-methyl-d-aspartate (NMDA) receptors, induction of cyclooxygenase and prostaglandin synthesis, and changes in gabanergic inhibition in the dorsal horns have all been implicated (Woolf).
We have no explanation for the so-called causalgia–dystonia syndrome (Bhatia et al) in which a fixed dystonic posture is engrafted on a site of causalgic pain. The clinical features of both the causalgic and dystonic elements of the syndrome have been somewhat unusual in the cases reported. The degree of injury was often trivial or nonexistent and no signs of a neuropathic lesion were evident. Remarkably, both the causalgia and dystonia spread from their initial sites to widely disparate parts of the limbs and body. The syndrome has not responded consistently to any form of treatment, although some patients recovered spontaneously. Another interesting type of causalgia and reflex sympathetic dystrophy follows deep venous thrombosis in a leg and had in the literature been recorded as “algodystrophy.” It may be similar to the left shoulder and hand changes that come on months after a myocardial infarction (“shoulder–hand syndrome”).
The treatment of reflex sympathetic dystrophy is largely unsatisfactory, although a certain degree of improvement can be expected if treatment is started early and the limb is mobilized. The options for treatment are discussed further on.