Potent analgesic effects of GDNF in neuropathic pain states

Neuropathic pain arises as a debilitating consequence of nerve injury. The etiology of such pain is poorly understood, and existing treatment is large ly ineffective. We demonstrate here that glial cell line-derived neurotroph ic factor (GDNF) both prevented and reversed sensory abnormalities that dev eloped in neuropathic pain models, without affecting pain-related behavior in normal animals. GDNF reduces ectopic discharges within sensory neurons a fter nerve injury. This may arise as a consequence of the reversal by GDNF of the injury-induced plasticity of several sodium channel subunits. Togeth er these findings provide a rational basis for the use of GDNF as a therape utic treatment for neuropathic pain states.