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

Anesth Analg. 2015 Sep;121(3):822-828. doi: 10.1213/ANE.0000000000000853.


Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Male
  • Neuralgia / chemically induced*
  • Neuralgia / drug therapy*
  • Neuralgia / pathology
  • Phosphodiesterase 4 Inhibitors / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Rolipram / therapeutic use*
  • Treatment Outcome


  • Antineoplastic Agents
  • Phosphodiesterase 4 Inhibitors
  • Rolipram