Behavioral characteristics and c-Fos expression in the medullary dorsal horn in a rat model for orofacial cancer pain

It is well known that patients with orofacial cancer suffer from cancer-induced pain which produces feeding difficulties. To understand the mechanisms of pain associated with orofacial cancer, we have recently created a model for rat orofacial cancer by inoculation with Walker carcinosarcoma 256B-cells into the vibrissal pads. The present study used both behavioral and immunohistochemical techniques to investigate changes in pain-related and ingestive behavior, along with c-Fos expression in the medullary dorsal horn which is a site for processing orofacial pain. The tumor mass grew gradually and contacted the nerve trunks within days after the inoculation of tumor cells. Physical difficulties in ingestion were observed after day 10 post-inoculation and facial grooming periods were prolonged. Sensitivities of the inoculated vibrissal pads to mechanical and thermal stimuli were increased on days 4 and 7, suggesting the development of mechanical allodynia and thermal hyperalgesia. Although hyposensitivity to mechanical and thermal stimulation was observed in the inoculated region after day 10, hyperalgesia developed on the margin of the tumor, suggesting that the hypersensitive region spread with growth of tumor mass. In the medullary dorsal horn, the levels of c-Fos immunoreactivity of the ipsilateral side increased significantly on days 4, 7 and 10, supporting the behavioral observations. These results indicate that the rat model shows symptoms similar to those in patients with orofacial cancer, for example, induction of feeding disorder and neuropathic pain.