Propentofylline, a glial modulating agent, exhibits antiallodynic properties in a rat model of neuropathic pain

The present study was undertaken to determine whether propentofylline, a gl ial modulating agent, could both prevent the induction of mechanical allody nia and attenuate existing mechanical allodynia in a rodent L5 spinal nerve transection model of neuropathic pain. In a preventative paradigm, propent ofylline (1 and 10 mg/kg intraperitoneally) was administered systemically d aily, beginning 1 day prior to nerve transection. This regimen produced a d ose-dependent decrease in mechanical allodynia (p < 0.01). in another preve ntative paradigm, propentofylline (0.1, 1, or 10 <mu>g) was administered da ily intrathecally via direct lumbar puncture. intrathecal administration of propentofylline was more effective than systemic administration at dose de pendently reducing mechanical allodynia (p < 0.01). The effect of systemic propentofylline on existing allodynia was examined with 0.1-, 1-, and 10-mg /kg intraperitoneal administration initiated on day 4 post L5 spinal nerve transection. Systemic propentofylline was found to be equally effective in the attenuation of existing allodynia (p < 0.01) as in the prevention of al lodynia in this rodent model of neuropathic pain. Spinal cords (L4-L6 segme nts) were removed for immunohistochemical analysis on day 10 or 20 post-tra nsection. Microglial and astrocytic activation was decreased by both periph eral and central administration of propentofylline in both preventative and existing allodynia paradigms. This research supports a growing body of lit erature highlighting the importance of glial activation in the development of persistent neuropathic pain states, and the potential to therapeutically modulate glial activation in the treatment of neuropathic pain.