The effect of Recombinant Botulinum Toxin A on neuropathic pain in Spared Nerve Injury mouse model

Hammer RE1, Richner M2, Vaegter CB2,3, Karlsson P1,4, Nyengaard JR1,5.

1. Core Center for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
2. Danish Research Institute of Translational Neuroscience, Nordic EMBL Partnership for Molecular Medicine, Department of Biomedicine, Aarhus University, Aarhus, Denmark.
3. The International Diabetic Neuropathy Consortium, Aarhus University Hospital, Aarhus, Denmark.
4. Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 
5. Center for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark.


Background and aims  
Neuropathic pain is a debilitating chronic pain disorder characterized by sensory abnormalities such as dysesthesia, hyperalgesia, and allodynia. Diabetic polyneuropathy (DPN) and traumatic nerve injury are some of the most common causes of neuropathic pain. The Db/Db model and the Spared Nerve Injury (SNI) model are validated animal models mimicking DPN and traumatic nerve injury, respectively. Published data indicate that botulinum toxin A (BoNT/A) has analgesic effects against peripheral neuropathic pain. 
This project aims to assess whether BoNT/A has an analgesic effect on the two mouse models representing neuropathic pain.

Methods
A total of 64 mice will be used (32 control mice (C57BL/6) and 32 Db/Db mice). In each group, 16 mice will be SNI operated while the remaining 16 will be sham-operated. In each group of 16, eight will receive either vehicle or 5 pg BoNT/A pr. mouse in 20 µL of gelatine phosphate buffer. Pain threshold will be assessed using Von Frey filaments and possible effects on the spinal cord, sciatic nerve, dorsal root ganglion, and brain will be evaluated using immunohistochemistry and quantitative light and electron microscopy.   
 
Results  
This is an ongoing study and the results will be presented at the conference. We hypothesize that rBoNT/A treatment will have an analgesic effect on both mouse models of neuropathic pain, compared with littermates that received placebo. 

Conclusions
If the hypotheses hold, this project will lay the groundwork for clinical testing in human patients with neuropathic pain.

THE EFFECT OF BOTULINUM TOXIN A ON NEUROPATHIC PAIN IN SPARED NERVE INJURY MOUSE MODEL