Different patterns of morphological changes in the hippocampus and dentate gyrus accompany the differential expression of disability following nerve injury

Abstract

Physical and psychological trauma which results in mood disorders and the disruption of complex behaviours is associated with reductions in hippocampal volume. Clinical evaluation of neuropathic pain reveals mood and behavioural change in a significant number of patients. A rat model of neuropathic injury results in complex behavioural changes in a subpopulation (~30%) of injured rats; these changes are co-morbid with a range of other 'disabilities'. The specific objective of this study was to determine in rats the morphology of the hippocampus and dentate gyrus in individuals with and without complex behavioural disruptions following a constriction injury of the sciatic nerve, and to determine whether rats that develop disabilities following nerve injury have a reduced hippocampal volume compared with injured rats with no disabilities. The social behaviours of nerve-injured rats were evaluated before and after nerve injury. The morphology of the hippocampus of rats with and without behavioural disruptions was compared in serial histological sections. Single-housing and repeated social-interaction testing had no effect on the morphology of either the hippocampus or the dentate gyrus. Rats with transient or ongoing disability identified by behavioural disruption following sciatic nerve injury, show bilateral reductions in hippocampal volume, and lateralised reduction in the dentate gyrus (left side). Disabled rats display a combination of behavioural and physiological changes, which resemble many of the criteria used clinically to diagnose mood disorders. They also show reductions in the volume of the hippocampus similar to people with clinically diagnosed mood disorders. The sciatic nerve injury model reveals a similarity to the human neuropathic pain presentation presenting an anatomically specific focus for the investigation of the neural mechanisms underpinning the co-morbidity of chronic pain and mood disorder.