A novel affective-motivational-based Overground System for detecting spinal cord injury-associated thermal and mechanical hypersensitivity in rats.

Abstract

Preclinical research for neuropathic pain has depended primarily on the use of behavioural nociceptive testing that is sensory-discriminatory-based and reflexive in nature. This can be particularly problematic in spinal cord injury (SCI)-associated neuropathic pain research where hyperreflexia may develop thus confounding interpretation of reflexive responses as pain symptoms. To address this, we have designed an affective-motivational-based Overground System that has interchangeable floors to allow examination of nociceptive behaviours in response to mechanical and cold stimuli prior to and following spinal cord injury. The animals were pretrained for 3-4weeks to cross three Overground System surfaces (cold, rough and neutral) at a consistent pace in order to obtain a food reward (Froot Loops™ ). Following SCI, crossing times were significantly decreased due to more rapid crossing over the cold surface despite forgoing of the food reward, in contrast with the sham control animals. This was correlated with the development of cold hypersensitivity as assessed by standard acetone droplet testing. In response to the rough surface, slower paced crossings (increased time to cross) were observed post-SCI (also resulting in forgoing of the food reward), compared to pre-SCI times and sham control animals. This was correlated with the development of mechanical hypersensitivity as assessed by standard von Frey testing. Different responses in crossing behaviour for the cold and rough surfaces suggest a precise adaptive change in decision-making behaviour depending on the stimulus presented; thus, outcome measures may be easily tailored for different types of hypersensitivity symptoms. We have designed an Overground System that is easy to establish and addresses a major concern in preclinical pain research by providing a cognitive- and motivational-based system for hypersensitivity detection. The affective-motivational-based Overground System allows examination of pain-like behaviours in response to cold (thermal) and rough (mechanical) stimulation prior to and following spinal cord injury. This system provides a more holistic and comprehensive assessment of nociceptive responses following SCI and helps overcome concerns of hyperreflexia confounding-evoked behavioural outcome measures in SCI models. Further, the incorporation of cognitive and motivational components brings preclinical research closer to replicating the clinical experience of a patient's motivation to participate in rewarding lifestyle activities in relation to their pain.