Influence of chronic peripheral nociceptive stimuli in the hippocampal neurogenesis

In most brain regions, the generation of neurons is generally confined to a discrete developmental period, and neuronal loss is thought to be irreversible in the adult human brain. However, a growing body of evidence suggests that new neurons with different neural phenotypes are continuously born through asymmetric cell division from progenitor cells located in two regions in adult mammals: the subventricular zone (SVZ) lining the lateral ventricles, and the subgranular zone of the hippocampal dentate gyrus (DG). In the hippocampus formation, new neurons generated locally at the border between the hilus and granule cell layer migrate into the granule cell layer where they develop morphological and biochemical characteristics of mature neurons. Previous reports have revealed that the rate of neurogenesis can be influenced by various environmental, endocrine, and pharmacological stimuli. Noxious stimulation always results in changes in gene expression within the central nervous system. Functional imaging and stimulation studies in humans have shown that multiple brain areas are activated by painful stimuli. In the present study, we therefore evaluated the effect of chronic peripheral nociceptive stimuli on environmental enrichment-induced hippocampal neurogenesis. Nerve-ligated mice were housed either in a standard environment or in the enriched environment for 4 weeks. Environmental enrichment increased the immunoreactivity for doublecortin, a marker for immature neuron and the number of NeuroD, a marker for immature granule cell precursors-positive cells in the DG. Under these conditions, chronic pain suppressed the increase in doublecortin-like immunoreactivity and number of NeuroD-positive cells by environmental enrichment in the DG We also found that chronic pain by sciatic nerve ligation caused an increase in glial fibrillary acidic protein (GFAP)-like immunoreactivity, which is located in the dendritic astrocytes, with its expanding distribution in the hippocampus of mice. These results suggest that chronic peripheral nociceptive stimuli inhibits the hippocampal neurogenesis in mice exposed to an enriched environment.