Innervation of hyperalgesic skin in patients with complex regional pain syndrome

Objective: To look for anatomical and histochemical signs of interaction between sensory and sympathetic nerves in the hyperalgesic skin of patients with complex regional pain syndrome. Subjects: Skin samples were obtained from eight patients whose condition developed after a suspected or confirmed peripheral nerve injury, and from nine patients with features of reflex sympathetic dystrophy (RSD) following a soft-tissue injury. A skin sample was also obtained from 18 control subjects of similar age and sex distribution to patients. Design: In patients, skin samples were taken from an area of static mechanical hyperalgesisa and from an equivalent site in the contralateral limb, In controls, skin samples were obtained from the dorsum of one hand or foot. Histochemical Markers: We used neuron-specific enolase for all classes of nerve fiber, tyrosine hydroxylase For nonadrenergic fibers; vasoactive intestinal peptide for sympathetic sudomotor fibers; tyrosine hydroxylase co-existing with neuropeptide Y For sympathetic vasoconstrictor fibers: and calcitonin gene-related peptide with substance P or somatostatin for peptide-containing unmyelinated sensory fibers. Results: In patients, the distribution of markers was similar in skin taken from an area of mechanical hyperalgesia and skin taken from an equivalent site contralaterally, and was unrelated to clinical features of RSD, The distribution of markers did not differ between patients and controls. Nerve tangles immunoreactive to neuron-specific enolase, but not to other markers, were detected in samples taken from four patients and two controls. The nerve tangles were present bilaterally in two patients, and only on the affected side in two other patients. The clinical condition was more fully developed in the four patients whose skin samples contained nerve tangles than in most other patients. Conclusions: a major difference in distribution or change in histochemical content of cutaneous autonomic or nociceptor fibers is unlikely to underly static mechanical hyperalgesia following a soft-tissue or peripheral nerve injury, The relevance of cutaneous nerve tangles for the pathophysiology of RSD is uncertain.