
Figure 1
Confocal images of human skin from normal (left) and diabetic (right) subjects.
Nerves in epidermis appear green and yellow, basement membrane separating the
epidermis from the dermis and also surrounding blood vessels appears red.
The top images have the most epidermal nerve fibers (ENFs) the bottom the least
from all subjects studied. Note the loss of ENFs in the diabetic subjects.
Scale bars equal 100µm.
Click here to see a higher resolution image (304K).

Figure 2
Neurolucida tracing of epidermal nerve fibers.

Figure 3a
Confocal images of blister roof, left low magnification (scale bar = 500µm)
survey image of a 3mm blister immunostained for nerve with antibody to protein
gene product 9.5. Rectangles indicate the areas imaged at 20x for nerve
counts. Right-higher magnification (scale bar = 100µm) image is used for
quantification of epidermal nerve fibers (from right rectangle in A).

Figure 3b
Confocal image of an immunostained sectioned blister. A. Nerves (protein gene
product 9.5 immunoreactivity) are green or yellow, basement membrane (type IV
collagen-immunoreactivity) is red. Epidermis separated from dermis just above
the dermo-epidermal basement membrane. Scale bar = 200µm. B. Dermal capillaries
and the subepidermal neural plexus remained intact. Scale bar = 100µm. C.
Epidermal nerves, severed from their proximal segment, remained in the blister
roof. Scale bar = 50µm.
Click here to see a higher resolution image (190K).

Figure 4
Confocal image of reinnervation following digital nerve lesion. Left: injured
finger, note fewer epidermal nerve fibers. Right: contralateral control displays
normal innervation pattern. Scale bar = 100µm.

Figure 5a
Biopsy of blister site. Nerve fibers in the new epidermis (right of arrow) were
leaning toward the center of the blister area. Many more epidermal nerve fibers
were present in the new epidermis than were seen at 6 days. Most reinnervation
proceeds from normal skin adjacent to the blister toward the center of the blister,
but some nerves enter from below.

Figure 5b
Reblister. Epidermal nerve fibers extended from the original blister edge (dotted
line) 600µm into the new epidermis. Nerve fibers were elongated and were oriented
toward the center of the original blister site.
Click here to see a higher resolution image (152K).

Figure 6
Reinnervation of a pig epidermis following reepithelization after blistering.
At left of the image epidermal innervation is normal (unblistered) the initial
blister is at the top center and extends to the right. Nerve fibers enter from
the normal epidermis (left) and form the subepidermal neural plexus and innervate
the periphery of the nascent epidermis. Nearer the center of the wound fewer nerves
were present (not shown). Scale bar = 100µm.