Pain Hypersensitivity is Associated with Increased Amygdala Volume and c-Fos Immunoreactivity in Anophthalmic Mice

Abstract

It is well established that early blindness results in brain plasticity and behavioral changes in both humans and animals. However, only a few studies have examined the effects of blindness on pain perception. In these studies, pain hypersensitivity was reported in early, but not late, blind humans. The underlying mechanisms remain unclear, but considering its key role in pain perception and modulation, the amygdala may contribute to this pain hypersensitivity. The first aim of this study was to develop an animal model of early blindness to examine the effects of blindness on pain perception. A mouse cross was therefore developed (ZRDBA mice), in which half of the animals are born sighted and half are born anophthalmic, allowing comparisons between blind and sighted mice with the same genetic background. The second aim of the present study was to examine mechanical and thermal pain thresholds as well as pain behaviors and pain-related c-Fos immunoreactivity induced by the formalin test in the amygdalas of blind and sighted mice. Group differences in amygdala volume were also assessed histologically. Blind mice exhibited lower mechanical and thermal pain thresholds and more pain behaviors during the acute phase of the formalin test, compared with sighted mice. Moreover, pain hypersensitivity during the formalin test was associated with increased c-Fos immunoreactivity in the amygdala. Furthermore, amygdala volume was larger bilaterally in blind compared with sighted mice. These results indicate that congenitally blind mice show pain hypersensitivity like early blind individuals and suggest that this is due in part to plasticity in the amygdala.

Keywords: amygdala; behavior; blind; nociception; pain; plasticity.