Reduction in touch sensitivity and hyperinnervation in vesicant-injured rabbit eyelid by direct injection of corticotropin releasing factor

Skin injury can result in inflammatory responses and increased sensitivity to touch. Corticotropin releasing factor (CRF), when administered locally or systemically, can reduce the inflammatory and hyperalgesic processes after skin injury. However, the mechanisms that control its effects are unclear. Doxorubicin injection produced inflammation, increased sensitivity to touch and more sensitive blink responses in eyelids of adult rabbits, and local injection of CRF reduced these changes. Doxorubicin alone resulted in a significant ingrowth of nerve fibers as determined by morphometric analysis of PGP 9.5 and substance P immunohistochemistry. Treatment with CRF significantly reduced this nerve fiber ingrowth, and a CRF antagonist partially blocked this protective effect. Thus, CRF has a potent tissue protective effect when administered locally after a vesicant-induced injury, and one mechanism of action is the reduction of nerve fiber ingrowth and sensitivity of the eyelid to touch.