Basic Science (31)

Abstract

Potent analgesic effects of GDNF in neuropathic pain states. (King's College London, London, United Kingdom) Science 2000;290:124–127.Neuropathic pain arises as a debilitating consequence of nerve injury. The etiology of such pain is poorly understood, and existing treatment is largely ineffective. We demonstrate here that glial cell line‐derived neurotrophic factor (GDNF) both prevented and reversed sensory abnormalities that developed in neuropathic pain models, without affecting pain‐related behavior in normal animals. GDNF reduces ectopic discharges within sensory neurons after nerve injury. This may arise as a consequence of the reversal by GDNF of the injury‐induced plasticity of several sodium channel subunits. Together these findings provide a rational basis for the use of GDNF as a therapeutic treatment for neuropathic pain states. Comment by Marshall Devor, PhD.Nerve injury frequently causes sensory neurons to become electrically hyperexcitable. The resulting ectopic afferent firing is thought to be the immediate cause of ongoing pain, movement‐evoked pain, and allodynia in neuropathic pain states. But why do the neurons become hyperexcitable? A popular hypothesis has it that when the axon is cut, the sensory cell body in the dorsal root ganglion (DRG) is starved of essential neurotrophic molecules that are normally produced in the periphery and transported to the DRG via axoplasmic transport. If so, then providing an exogenous source of the critical neurotrophin should prevent, or even reverse, the hyperexcitability and the pain. Boucher et al tried this, administering 1 of 3 candidate neurotrophins (NGF, NT‐3, or GDNF) by the intrathecal (i.t.) route. One of them, GDNF, worked dramatically. The authors believe that i.t. GDNF acts by diffusing into the DRG (rather than the spinal cord) where it alters the expression of the channel proteins that are responsible for electrical hyperexcitability.