Environmental enrichment reduces mechanical hypersensitivity in neuropathic mice, but fails to abolish the phenotype of CCK₂ receptor deficient mice

Genetic invalidation of CCK₂ receptors abolishes chronic constriction injury (CCI) induced mechanical hypersensitivity in mice. However, housing in environmentally enriched conditions significantly alters the phenotype of CCK₂ receptor deficient mice in all major behavioral domains. Furthermore, environmental enrichment itself has been reported to have protective effects in several rodent models of neurological diseases (brain and spinal trauma, ischemic stroke, Alzheimer's disease, etc.). In the present study we reproduced the earlier finding that mice, lacking CCK₂ receptors (-/-) are resistant to CCI-induced hypersensitivity. On the other hand, environmental enrichment substantially reduced CCI-induced mechanical hypersensitivity in wild-type (+/+) mice. Nevertheless, the phenotypic differences between wild-type (+/+) and mutant (-/-) mice in mechanical sensitivity before and after CCI-surgery were not eliminated by alternative housing conditions. These observations suggest that environmental enrichment has beneficial effects in neuropathic conditions and reinforce the causal link between CCK₂ receptors, mechanical sensitivity and the development of CCI-induced hypersensitivity.