A clinically-relevant model of neuropathic pain in pigs
The pig is the ideal species for neuropathic pain studies due to the many similarities between pig and human. The skin innervation is quite similar from pig to human with C-fiber classes between human and pig correlated in both distribution and axonal excitability changes. The pig sciatic nerve after 6 months of sustained hyperglycemia exhibits alterations in fiber density often observed in human patients with long-term diabetes. Other organ systems such as the cardiovascular system, pancreas, vascular and immune system are very similar between human and pigs.
It is well-known that the failure rate at clinical stages is high (>80%) and costly to biopharma companies. There is a need for more clinically relevant models at preclinical stages to help reduce the candidates that are brought into clinical stages. The large animal model for neuropathic pain presents biopharma companies with the opportunity to study in a more relevant model with fewer limitations on obtaining efficacy and PK data from the same animal. It is ideal for testing local therapies, slow release drug/device combinations as well as systemic therapies aimed at sciatica-related pain in humans.
Sciatic nerve injury is created by partial ligation to the sciatic nerves with CFA coated sutures. This method provides a stable and controlled pain for at least 28 days. The model is suitable for a variety of therapies including local therapies to the nerve.
The model has the following advantages:
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Morphine was administered at 1 mg/kg intramuscularly on day 28. Von Frey was measured and morphine reversed the response by nearly 50% compared to untreated animals.