It is well known that exposure to maternal separation (MS) in early life causes
plastic changes in the nervous system in adulthood, occasionally resulting in ubiquitous
chronic pain. However, the pathogenic mechanisms of
pain hypersensitivity remain unclear. Here, the authors examined the involvement of
corticosterone in orofacial mechanical
hypersensitivity induced by MS. To establish a rat model of MS, pups were placed in isolated cages 180 min/d and kept in a temperature-controlled environment at 22 ± 2 °C for 14 d.
Mechanical allodynia in the whisker pad skin in adulthood was induced by MS and was significantly suppressed by successive postnatal subcutaneous administration of the
glucocorticoid receptor antagonist
mifepristone.
Corticosterone levels were increased in the serum of MS rats, and successive postnatal administration of subcutaneous
corticosterone to naive rats induced
mechanical allodynia in the whisker pad skin. The number of
P2X3 receptor-immunoreactive (P2X3R-IR) trigeminal ganglion (TG) neurons innervating the whisker pad skin was significantly increased in MS rats and decreased following subcutaneous administration of
mifepristone. The number of P2X3R-IR TG neurons innervating the whisker pad skin was also significantly increased following successive postnatal administration of subcutaneous
corticosterone in naive rats. Moreover, the
mechanical allodynia was suppressed 30 min after administration of the P2X3R antagonist
A317491 to the whisker pad skin in MS rats. These findings suggest that the increase in P2X3R-IR TG neurons innervating the whisker pad skin via enhanced neonatal
corticosterone signaling by MS plays an important role in orofacial
mechanical allodynia in adulthood.