The Analgesic Effect of Rolipram, a Phosphodiesterase 4 Inhibitor, on Chemotherapy-Induced Neuropathic Pain in Rats.

Abstract

Chemotherapy-induced neuropathic pain is a significant side effect of chemotherapeutic agents. Currently, there are no effective analgesics for chemotherapy-induced neuropathic pain. Rolipram is a selective phosphodiesterase 4 inhibitor, which increases intracellular cyclic AMP in nerve and immune cells. The aim of our study was to determine the analgesic effects of rolipram on paclitaxel (PAC)-induced neuropathic pain in rats. Chemotherapy-induced neuropathic pain was produced by intraperitoneal injection of PAC on 4 alternate days in male Sprague-Dawley rats. Mechanical allodynia was measured by using von Frey filaments. After the rats developed PAC-induced pain behavior (such as mechanical allodynia), a single intraperitoneal injection and continuous infusion of rolipram ameliorated PAC-induced pain behavior. In addition, systemic infusion of the drug during the early phase of developing pain behavior did not prevent the development of mechanical allodynia induced by PAC. These results suggest that rolipram alleviated mechanical allodynia induced by PAC in rats. Thus, phosphodiesterase 4 inhibitors may prove useful in the treatment of chemotherapy-induced neuropathic pain. However, further studies are needed to clarify their effects in clinical settings.