Reflex Sympathetic Dystrophy
abstract & commentary
Source: Goldstein DS, et al. Sympathetic innervation and function in reflex sympathetic dystrophy. Ann Neurol 2000; 48:49-59.
Sympathetic neurocirculatory function was examined by positron emission tomography ([PET] in 9 men and 21 women), aged 25-55 years, with reflex sympathetic dystrophy (RSD). 13N-ammonia (a perfusion imaging agent) and 6-[18F]flourodopamine (a sympathoneural imaging agent) were used to assess local perfusion and sympathetic innervation. The rate of norepinephrine spillover that escaped into the venous system from neuronal reuptake was estimated during intravenous infusion of 3H-norepinephrine. Local norepinephrine turnover was examined by regionally measuring its main metabolite, dihydroxyphenylglycol; local norepinephrine synthesis was examined by regionally measuring L-dihydroxyphenylalanine. Both were measured before and after ganglionic blockade using intravenous trimethaphan, to determine whether RSD pain is maintained by sympathetic nerve traffic.
RSD was diagnosed on the basis of persistent, post-traumatic pain that spread beyond the distribution of any single nerve (complex regional pain syndrome, type I) associated with hair loss, dystrophic skin or nail changes, altered sweating or skin color or temperature, swelling, allodynia, and disuse muscle atrophy. Patients continued taking pain medication during the study but adrenoreceptor-active drugs and tricyclic antidepressants were discontinued. Comparison was made to the contralateral limb, age-matched normal controls, and previously reported normal data. Statistical analysis used dependent-means T tests and repeated measures ANOVAs.
PET scanning using 13N-ammonia radioactivity was decreased, and perfusion adjusted 6-[18F]flouro-dopamine was increased on the affected side. This indicated decreased perfusion in the affected limb in the presence of a normal amount of sympathetic terminal innervation. No differences were appreciated between affected and unaffected limbs in norepinephrine spillover, dihydroxyphenylglycol, or L-dihydroxyphenylalanine plasma levels. Trimethaphan decreased pain in only two of 12 previously sympathectomized patients, indicating a pain mechanism independent of postganglionic nerve traffic. In RSD, sympathetic innervation and norepinephrine synthesis is symmetrical, sympathetic terminal innervation remains intact, and perfusion is decreased. This indicates that pain is generally independent of sympathetic outflow in most cases of RSD. Complex regional pain syndrome is, thus, the preferred term for this baffling disorder.
Commentary
Sympathectomy may be beneficial in RSD, not due to the significance of the sympathetic nervous system in maintaining the pain, but rather due to placebo effect or deafferentation of primary visceral fibers that run with sympathetic nerves (BMJ 1998;316:792-793). Infusion of phenylephrine, an alpha-1 adrenergic agonist that should exacerbate sympathetically maintained pain, did not do so in 29 patients with causalgia, RSD, or polyneuropathy (Neurology 1994;44:1010-1014). Indeed, saline sympathetic blocks produced an average of 20 hours of relief in RSD (Clin J Pain 1998;14:216-226) and meta analysis of sympathectomy in RSD found it lacking (Pain 1997;73:123-139). Support for sympathetic involvement in RSD is shown by thermal hyperalgesia being enhanced by adrenergic agonists in capsaicin-treated skin (J Auton Nerv Syst 1998;69:96-102), and dampened by phentolamine (Pain 1997;69:79-85). These data, however, are refuted by elegant studies showing that natural stimulation of sympathetic efferents, by heating and cooling in a thermal suit, did not affect pain or hyperalgesia in capsaicin-treated areas. Has the sympathetic hypothesis been put to rest? Not yet, but it does appear to be fading. Meanwhile, whether the diagnosis is called causalgia, traumatic angiospasm, acute trophoneurosis, or postinfarctional sclerodactyly, we believe that for the present, the terms complex regional pain syndrome type I (pain spreading beyond the site of injury), or type II (causalgia caused by a peripheral nerve injury) remain as appropriate labels. —michael rubin
Reflex sympathetic dystrophy:
a. is due to capsaicin induced hyperalgesia.
b. is due to hyperactivity of phenylephrine, an alpha-1 adrenergic agonist.
c. is due to deafferentation of primary visceral fibers with resultant sympathetic fiber disinhibition.
d. may have nothing to do with the sympathetic nervous system.
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