Assessment and analysis of mechanical allodynia-like behavior induced by spared nerve injury (SNI) in the mouse

Experimental models of peripheral nerve injury have been developed to study mechanisms of neuropathic pain. In the spared nerve injury (SNI) model in rats, the common peroneal and tibial nerves are injured, producing consistent and reproducible pain hypersensitivity in the territory of the spared sural nerve. In this study, we investigated whether SNI in mice is also a valid model system for neuropathic pain. SNI results in a significant decrease in withdrawal threshold in SNI-operated mice. The effect is very consistent between animals and persists for the four weeks of the study. We also determined the relative frequency of paw withdrawal for each of a series of 11 von Frey hairs. Analysis of response frequency using a mixed-effects model that integrates all variables (nerve injury, paw, gender, and time) shows a very stable effect of SNI over time and also reveals subtle divergences between variables, including gender-based differences in mechanical sensitivity. We tested two variants of the SNI model and found that injuring the tibial nerve alone induces mechanical hypersensitivity, while injuring the common peroneal and sural nerves together does not induce any significant increase in mechanical sensitivity in the territory of the spared tibial nerve. SNI induces a mechanical allodynia-like response in mice and we believe that our improved method of assessment and data analysis will reveal additional internal and external variability factors in models of persistent pain. Use of this model in genetically altered mice should be very effective for determining the mechanisms involved in neuropathic pain.