Controllable forces for reproducible chronic constriction injury mimicking compressive neuropathy in rat sciatic nerve

Background: Compressive neuropathy is a recurring and challenging disease for patients, regardless of medical or surgical treatment. Neuropathological severity is associated with the force of mechanical compression. Available animal models do not address mechanical issues with reproducible outcomes. We used a chronic constriction injury model to analyze tension-controlled compressive neuropathy and achieve reproducible functional outcomes. New method: We refined a modified animal model for chronic constriction nerve injury under controllable compressive tensile strength to target the unilateral sciatic nerve of adult rats. Sensory outcomes were evaluated using the Von Frey test. Muscle atrophy and nerve degeneration were analyzed, including markers of neural degeneration, neuroinflammation, and neuropathic pain in the affected nerve. Results: The compressive force significantly affected the neuropathological severity of sensory dysfunction and muscle atrophy. Greater mechanical forces (i.e., tight-knot) contributed to muscle atrophy and hypoesthesia. Low forces (i.e., loose-knot) induced mechanical allodynia with better residual muscle weight. Well-controlled loose knotting can avoid myelin degradation while lessening neuroinflammation and macrophage infiltration. Neuropathic pain was enhanced with increased nociceptive pain markers expression within the affected nerve. Comparison with Existing Method(s): Our chronic constriction injury model, unlike previous models, controls the ligation forces applied for different levels of injury. Conclusion: The functional influences of different compressive forces recapitulate the diverse clinical symptoms involved in clinical compressive neuropathy. This controllable and reproducible model of compressive neuropathy revealed the underlying molecular mechanisms of neural degeneration and inflammation. It will lead to the future development of translational therapeutics for neuropathic pain and nerve regeneration.