Oral mucositis is one of the most common side effects of chemoradiation
regimens and manifestation can be dose-limiting for the therapy, can impair
the patient's nutritional condition and quality of life due to severe pain.
The therapeutic options are limited; often only an alleviation of the symptoms
such as pain reduction by using systemic opioids is possible. Stimulating
opioid receptors on peripheral neurons and dermal tissue, potent analgesic
effects are induced e.g. in skin grafted patients. Advantageous effects on the
cell migration and, thus, on the wound healing process are described, too. In
this study, we investigated whether opioid receptors are also expressed on
oral epithelial cells and if morphine can modulate their cell migration
behavior. The expression of the opioid receptors MOR, DOR and KOR on primary
human oral epithelial cells was verified. Furthermore, a significantly
accelerated cell migration was observed following incubation with morphine.
The effect even slightly exceeded the cell migration stimulating effect of
TGF-ß: After 14 h of morphine treatment about 86% of the wound area was
closed, whereas TGF-ß application resulted in a closed wound area of 80%. With
respect to morphine stimulated cell migration we demonstrate that DOR plays a
key role and we show the involvement of the MAPK members Erk 1/2 and p38 using
Western blot analysis