Sheep Model for Neuropathic Pain Testing
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Solution Overview
Problem
Current animal models for neuropathic pain, particularly in rodents, are limited in predicting human efficacy and safety due to size differences and genetic diversity, and lack a suitable large mammalian model for testing therapeutic alternatives before clinical trials.
Innovation Solution
A sheep model of neuropathic pain is developed by transecting the common peroneal nerve, allowing for the use of existing clinical drug delivery systems and measuring behavioral changes in mechanical allodynia and hyperalgesia using von Frey filaments and pin-pricks, enabling the testing of drug efficacy and safety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If rodent models are used for neuropathic pain research, then cost and ease of handling are improved, but predictive accuracy for human clinical trials deteriorates
Solution Approach 1:
The patent changes the key parameter of animal model selection from small rodents to large mammals (sheep, goats, pigs), fundamentally altering the scale and physiological relevance of the model system to better predict human clinical responses while maintaining experimental feasibility
2Quantity of substance
If rodent models are used for neuropathic pain research, then experimental cost is reduced, but generalizability to human patients deteriorates
Solution Approach 1:
The patent changes the scale parameter from small rodents to large mammals, improving generalizability to human patients through greater anatomical and physiological similarity, while managing costs through controlled experimental designs and the use of commercially available analgesic compounds
3Reliability
If large mammalian models are used for neuropathic pain research, then predictive accuracy for human trials is improved, but experimental cost and complexity increase
Solution Approach 1:
The patent segments the experimental protocol into distinct phases: nerve injury induction, behavioral baseline assessment, treatment administration, and outcome measurement. This segmentation manages complexity by breaking down the overall experimental process into manageable, standardized components
Solution Approach 2:
The patent employs commercially available analgesic compounds and standardized behavioral assessment protocols that can be applied across different large mammalian species, creating a universal framework that reduces experimental complexity while maintaining predictive accuracy
4Adaptability or versatility
If existing clinical drug delivery systems are used in sheep models, then translational relevance to human medicine is improved, but dosing precision and safety margins deteriorate
Solution Approach 1:
The patent changes the dosing parameter scale from rodent-equivalent doses to human-equivalent doses, improving translational relevance by using clinically relevant dosing regimens, while implementing careful monitoring and adjustment protocols to maintain dosing precision and safety
Solution Approach 2:
The patent implements feedback mechanisms through behavioral assessment and clinical monitoring to adjust dosing in real-time, ensuring precision and safety while maintaining translational relevance through the use of human-equivalent dosing protocols
Data Source
AI summary
Methods for producing peripheral nerve injury in sheep are provided. The sheep model provides a model of persistent neuropathic pain in humans. Methods for drug delivery are provided. Also provided is a method for screening potentially therapeutic agent for the treatment of persistent neuropathic pain. Also provided are the methods for measuring the changes produced by neuropathic pain.