Background: The sympathetic innervation of the hand was demonstrated using formaldehyde staining techniques in the 1990s and provides a basis for both medical (botulinum toxin type A) and surgical (sympathectomy) therapeutic approaches. This research investigates the sympathetic innervation of the human foot using tyrosine hydroxylase immunohistochemistry. METHODS:: With institutional review board approval, six freshly amputated lower extremities had arterial, venous, and peripheral nerve biopsies obtained at the distal leg, ankle, and forefoot levels. Tibial, peroneal, sural, and saphenous nerves were processed immediately for immunohistochemical staining using an anti-tyrosine hydroxylase antibody, for light and electron microscopy evaluation. Qualitative assessments noted the presence or absence of tyrosine hydroxylase-positive fibers in artery, vein, and peripheral nerve. Within the nerve, location of the tyrosine hydroxylase staining was noted. RESULTS:: The presence of tyrosine hydroxylase-positive material was identified in each artery, vein, and nerve examined at each level of the foot and ankle. For the artery, the staining was in the adventitia, and rarely in the media of the vessel wall. There were clear entry points into the artery from the connective tissue. For the vein, the staining was more evenly distributed but to a lesser intensity than in the artery. Within each nerve at the proximal levels, the staining was diffusely throughout the fascicles, with clear sites of fibers leaving the periphery. CONCLUSIONS:: It is concluded that (1) sympathetic innervation of the foot arrives along each peripheral nerve, (2) the vessels already contain sympathetic innervation at the level of the ankle, and (3) the sympathetic innervation of the foot is extensive.
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