Peripheral nerve pathology in sickle cell disease mice
Katelyn E Sadler1, Tylor R Lewis2, Tyler B Waltz1
1Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.
Pain Reports
|October 4, 2019
Summary
Sickle cell disease (SCD) causes neuropathic pain due to peripheral nerve damage. SCD mice exhibit thinner myelin sheaths and myelin instability, indicating a model for neuropathy.
Area of Science:
- Neuroscience
- Hematology
- Pathology
Background:
- Sickle cell disease (SCD) patients frequently experience chronic neuropathic pain.
- Peripheral sensory neurons transmit pain signals, but SCD-related neuropathy is not well-characterized.
- No prior studies have systematically examined peripheral nerves in SCD models or patients.
Purpose of the Study:
- To investigate peripheral nerve morphology in a mouse model of sickle cell disease (SCD).
- To compare nerve structure between transgenic SCD mice and control animals.
Main Methods:
- Light and transmission electron microscopy of sciatic nerves.
- Western blot analysis for myelin basic protein expression.
- Assessment of blood-nerve barrier permeability using Evan's blue.
Main Results:
- SCD mice displayed thinner myelin sheaths and myelin instability (infolding, unwrapping).
- Deficits in nonmyelinating Schwann cells and reduced C fibers in Remak bundles were observed.
- Increased blood-nerve barrier permeability and myelin basic protein expression were noted in SCD nerves.
Conclusions:
- Berkeley SCD mice serve as a natural model for peripheral neuropathy.
- Widespread myelin instability in SCD nerves may result from increased blood-nerve barrier permeability.
- This suggests circulating demyelinating agents access sensory afferents in SCD.
