A Skin Blister Method for Quantification of Epidermal Nerves


We believe the blister method will be useful for diagnosing neuropathy and as a model for studying skin injury. There are several advantages of the skin blister over the standard skin biopsy:

  1. Non-invasive - only the epidermis is removed. Since the nerves have pulled free from their proximal connections, no pain is felt.
  2. Epidermis specificity - the standard skin biopsy includes both epidermis and dermis whereas the blister removes only epidermis
  3. Sample Size - The sampled area is much larger than the epidermal surface represented in a thick section from a skin biopsy.


Creation of a Suction Blister


A suction capsule is attached

After about an hour, the capsule is removed

The roof of the blister is removed. It doesn't hurt - the nerves in the roof of the blister have pulled loose from their proximal connections.

The blister is flattened under a coverslip and immunostained.


Sensory Test Correlation

We are currently studying the correlation between number of nerves in a blister and the results of these sensory tests.


Blister in Cross Section

This blister profile is a thick section of a skin biopsy of a blister. the separation plane is just above the basement membrane stained red for collagen IV. Epidermal nerves are in the blister roof. Basement membrane and capillary loops are intact.


Nerves in a Blister Roof

The excised, whole mounted blister roof is immunostained for protein gene product 9.5 and examined en face to count the number and determine the distribution of ENFs.

This is normal.

This shows a mild diabetic neuropathy.

Severe neuropathy.


We have submitted a paper to the Annals of Neurology describing our development of the skin blister method. It is currently under review. Click here to see the abstract


Home University of Minnesota Medical School
Department of Neurology
Last updated: December 10, 1997
Webmaster: eric@kennedysg.med.umn.edu