P75 AND TRKA NEUROTROPHIN RECEPTORS IN HUMAN SKIN AFTER SPINAL-CORD AND PERIPHERAL-NERVE INJURY, WITH SPECIAL REFERENCE TO SENSORY CORPUSCLES

Human skin, including nerves and sensory corpuscles, displays immunore activity (IR) for low- (p75) and high-affinity (TrkA-like) receptors f or nerve growth factor (NGF), the best characterized member of the fam ily of neurotrophins. This study was designed to analyze the changes i nduced by spinal cord and peripheral nerve injuries in the expression of neurotrophin receptors in digital skin, with special reference to n erves and sensory corpuscles. Skin biopsy samples were obtained from 1 ) the hand and toes of normal subjects, 2) below the level of the lesi on of patients with spinal cord injury affecting dorsal and lateral fu niculi, 3) the cutaneous territory of entrapped peripheral nerves (med ian and ulnar nerves), and 4) the cutaneous territory of sectioned and grafted nerves (median nerve). The pieces were formalin fixed and par affin-embedded, cut in serial sections, and processed for immunohistoc hemistry using antibodies against human p75 and TrkA proteins. The per centage of sensory corpuscles displaying IR for p75 and TrkA-like, as well as the intensity of IR developed within them, was assessed using quantitative image analysis. Spinal cord severance causes a decrease i n p75 IR in Meissner and Pacinian corpuscles, whereas TrkA-like IR did not vary. In other nonnervous tissues (i.e., epidermis, sweat glands) , both p75 and TrkA-like IR was diminished or even absent. Similar but more severe changes were encountered in the skin from the territory o f entrapped nerves. Finally, in subjects with sectioned-grafted nerves , p75 IR was found close to controls in nerves, reduced in Meissner co rpuscles, and absent in the inner core of the Pacinian ones; TrkA-like IR was in the perineurium, a small percentage of Meissner corpuscles (about 7%), and the outer core and capsule of the Pacinan corpuscles. In the nonnervous tissues, p75 IR was practically absent, whereas TrkA -like IR did not change. No changes in the expression of neurotrophin receptors were observed in Merkel cells of the different groups. Prese nt results show the following: 1) expression of nerve p75 IR in human cutaneous sensory corpuscles is sensitive to central deafferentation, to blockade or difficulty in axonal transport, and to disruption of ax onal continuity independently of possible restoration of axonal integr ity due to grafts; 2) expression of TrkA-like IR in nerves and sensory corpuscles is sensitive only to nerve transection; 3) the corpuscular Schwann-related cells are the only cells involved in the above modifi cations, the perineurial cells remaining unchanged; 4) the expression of p75 and TrkA-like IR by Merkel cells is independent of normal inner vation; 5) an adequate innervation of the skin seems to be necessary f or the expression of p75 but not TrkA-like in nonneuronal cells, espec ially in the epidermis. A role for NGF in the maintenance of epidermis integrity is discussed. Anat. Rec. 251:371-383, 1998. (C) 1998 Wiley- Liss, Inc.