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Perineural Application Of Minimally Processed Fat Tissue To Mitigate Neuropathic Pain In A Rat Model Of Neuroma
Amir Dehdashtian, M.D., M.P.H, Justin P. Wisely, BS, Shelby R. Svientek, MD, Erin L. Guy, BS, Anna E. Riegger, BS, Jagienka H. Timek, BS, Paul S. Cederna, MD, Stephen WP Kemp, PhD.
University of Michigan, Ann Arbor, MI, USA.

PURPOSE:
Neuroma-induced neuropathic pain is challenging to manage. Although animal studies have shown the benefits of adipose derived stem cells (ADSCs) to prevent neuropathic pain, there are many regulatory barriers to use in humans. To date, only minimally manipulated fat tissue is approved for human use by the FDA. Limited clinical studies have suggested perineural fat grafting attenuates end-neuroma pain. Unfortunately, most approaches to fat grafting employ the use of the stromal vascular fraction (SVF) where enzymatic digestion of fat is used to increase the concentration of ADSCs. This intervention is not considered "minimal manipulation". The aim of this study was to investigate the effect and the underlying mechanisms of minimally manipulated autologous fat grafts to reduce neuroma pain in a rat model.
METHODS:
Twenty-four Lewis rats were randomly assigned to the following groups: (1) saline-treated neuroma, (2) fat-treated neuroma, (3) SVF-treated neuroma, and (4) sham-operated control. Bilateral inguinal fat pads of 6 donor rats were harvested, and each side was used for each rat requiring either SVF or fat grafting. Initially, all rats underwent baseline behavioral testing including: neuroma site tenderness similar to the Tinel test; Von-Frey test for mechanical allodynia; Hargreaves test for thermal allodynia; and acetone test for cold allodynia. Subsequently, all neuroma groups underwent surgery to create a neuroma by transecting the tibial nerve at the mid-thigh level and securing the proximal end to the dermis of the lateral thigh skin. Each fat treated rat received fat grafts around the nerve ending, whereas the SVF and saline treated groups received SVF or saline loaded gelatin scaffolds, respectively (Figure). Following 8 weeks of behavioral testing, the neuroma bulb, tibial nerve, L4 and L5 dorsal root ganglions, and lumbar spinal cord were harvested for immunohistochemistry and western blotting.
RESULTS:
Both perineural fat grafting and SVF treatment significantly mitigated neuroma site pain with fat grafting showing a delayed benefit compared to the SVF treatment. Neither SVF nor fat grafting prevented paw hypersensitivity. Moreover, the size of the neuroma bulb was significantly decreased in both treatment groups (Figure).
CONCLUSION:
Minimally manipulated autologous fat grafts and SVF can substantially mitigate neuroma pain in rats. The observed delayed effect of fat grafting is possibly due to the higher concentration of ADSCs in the SVF.


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