Antiallodynic effects of propentofylline Elicited by interrupting spinal glial function in a rat model of bone cancer pain.

The activation of microglia and astrocytes in the spinal cord is involved in the progress of cancer pain. Propentofylline (PPF), a glial modulating agent, alleviates pain hypersensitivity in neuropathic pain models. The present study investigated the potential roles of PPF in a preclinical rat model of bone caner pain established by inoculating Walker 256 cells into the left tibia. At day 9 postinoculation, single administration of PPF (10 μg/10 μl, i.t.) significantly but transiently suppressed mechanical allodynia induced by bone cancer. Repeated application of PPF (10 μg/10 μl, i.t., once daily from days 9 to 12) persistently relieved mechanical allodynia on the side ipsilateral to surgery. Immunohistochemistry and ELISA showed that microglia and astrocytes in the spinal cord were activated, and the production of glia-derived proinflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) markedly increased at day 12 postinoculation in the cancer group. Intrathecal injection of PPF (10 μg/10 μl) significantly inhibited the activation of spinal glial cells and the expression of proinflammatory cytokines. These results suggest that the glial modulating agent PPF has antiallodynic effects on bone cancer pain and has potential utility for clinical treatment of cancer pain.