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Sciatica model of Neuropathic Pain

The induction of neuropathic pain in the sciatica model is done by creating injury directly on the sciatic nerve, minimizing any inflammatory component. Nerve injury can be created by either crushing of the sciatic nerve in two locations with a non-traumatic clip or by cutting the sciatic nerve. The nerve crush method produces a less pronounced pain and the animals will recover from the procedure more quickly than the nerve cutting method. Additionally, for therapies that are thought to be neuroprotective or promote nerve regeneration, partial nerve damage using the nerve crush method will allow direct treatment to the nerve.

The pig was the chosen species for this model due to the similarities in innervation as well as other systems such as the skin and cardiovascular system. This model is suitable for evaluating efficacy and PK/PD in the same study providing more clinical relevant data.

Model Specifications

  • Model length - up to 21 days
  • Positive control: morphine
  • Readouts*: Von Frey, cold allodynia, pin prick, weight bearing
  • Endpoints: histology, biomarker analysis (protein or mRNA levels in sciatic nerve or serum/plasma)

 

Von Frey in the sciatica model: nerve crush vs nerve cut
Figure: Von Frey measurements for pre-and post treatment with 1 mg/kg morphine.

 

*all models include body weights and clinical signs. Von Frey can be evaluated using either the up/down or Dixon method.