Basic NeuroscienceShort communicationA method to enhance the magnitude of tactile hypersensitivity following spinal nerve ligation in rats

- We propose a technique of post-ligation manipulation of SNL rats which enhances tactile hypersensitivity, and leads to a magnification of the signal window.
- This larger window is optimized for the evaluation of putative analgesics.
- In spite of the enhanced sensitivity, the clinical reference standard, Neurontin®, continues to nearly fully reverse the tactile hypersensitivity behavior.
- The method described satisfies both reduction and refinement principles as the number of ligated animals needed for any given study is significantly reduced.

BackgroundThe rat L5/L6 spinal nerve ligation model (SNL) has been widely used to investigate putative analgesics. Pursuit of novel therapies in preclinical settings requires models with consistent and reproducible phenotypes.New methodWe assessed the effects of repetitive stimulation of the hindpaws of SNL and Sham surgery rats during the 2 weeks immediately after surgery on the overall rate of achieving tactile hypersensitivity, as well as the magnitude of the hypersensitivity compared to unprimed rats. Beginning on day 2 post-surgery, and continuing on alternate days for a total of seven sessions, animals underwent light brushing/tapping (termed priming) of the hindpaws ipsilateral and contralateral to surgery.ResultsPriming the ipsilateral hindpaw enhanced the magnitude of tactile hypersensitivity such that the baseline withdrawal threshold (BWT) for primed SNL animals was significantly lower than unprimed SNL animals over post-surgical days 15-29. BWT was not different between primed and unprimed Sham rats. The percentage of SNL primed animals meeting the a priori criterion for tactile hypersensitivity of paw withdrawal threshold less than 2.0 grams was 98.9% ± 1.1%.Comparison with existing methodSNL rats that did not receive stimulation (unprimed) showed significantly higher baseline hypersensitivity when evaluated on days 15-29, exemplified by only 34.5% ± 7.2% meeting the established <2.0 g criterion.ConclusionOur data indicate that tactile priming during the 2 weeks immediately after SNL surgery enhances the magnitude of tactile hypersensitivity in the SNL model, and provide an optimized assay for evaluating putative analgesics.