The present research proposal consists of a series of studies on cutaneous sensory receptors comparing the processes of normal development with the processes of degeneration and regeneration of sensory axon terminals. The sequence of changes that occur during normal development of sensory nerve endings in the monkey embryo will be used as a baseline for analyzing the process of regeneration. The sequence of cytodifferentiation of axons and associated Schwann, lamellar and Merkel cells will be followed in glabrous and hairy skin. The acute changes in sensory axon terminals and associated lamellar, Schwann or Merkel cells that occur following nerve transection or removal of dorsal root ganglia will be analyzed during the first few hours following nerve transection. The pattern of innervation of hairs and glabrous skin in chronic partial deafferentation will be studied to verify the presence or absence of sensory axonal sprouting. The process of regeneration of partially deafferented and normally innervated skin will be compared following nerve transection and nerve crush. A normal pattern of peripheral sensory terminals should result from crushing of the nerve and an abnormal pattern of reinnervation should occur following transection of the ulnar or median nerve at the wrist. The status of the sensory receptors in reinnervated skin will be correlated with known physiologic studies of the results of nerve crush as compared to nerve transection. However, the process of regeneration into a cutaneous field that is partially deafferented may well be different especially if peripheral sprouting does indeed occur. These experimental studies will be based largerly in the rhesus monkey and will be used to better understand the sensory status of human skin from cases of trauma or disease of peripheral nerves. Suitable surgical or autopsy specimens will be used to provide examples of the stages of development of human cutaneous sensory receptors for comparison with the more extensive monkey series. The acute as well as chronic states of partial deafferentation of human skin will be studied in patients following detailed clinical testing of the sensory functions of their skin.
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