Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Action Potentials / drug effects
-
Analgesics, Non-Narcotic / pharmacology
-
Analgesics, Non-Narcotic / therapeutic use*
-
Animals
-
Ganglia, Spinal / physiopathology
-
Glial Cell Line-Derived Neurotrophic Factor
-
Hot Temperature
-
Hyperalgesia / drug therapy*
-
Ligation
-
Nerve Fibers / drug effects
-
Nerve Fibers / physiology
-
Nerve Fibers, Myelinated / drug effects
-
Nerve Fibers, Myelinated / physiology
-
Nerve Growth Factors*
-
Nerve Tissue Proteins / pharmacology
-
Nerve Tissue Proteins / therapeutic use*
-
Neural Conduction / drug effects
-
Neurons, Afferent / drug effects
-
Neurons, Afferent / physiology
-
Pain / drug therapy*
-
Pain Threshold / drug effects
-
Peripheral Nervous System Diseases / physiopathology*
-
Rats
-
Reverse Transcriptase Polymerase Chain Reaction
-
Sciatic Nerve
-
Sodium Channels / genetics
-
Sodium Channels / metabolism
-
Spinal Nerves
-
Touch
Substances
-
Analgesics, Non-Narcotic
-
Gdnf protein, rat
-
Glial Cell Line-Derived Neurotrophic Factor
-
Nerve Growth Factors
-
Nerve Tissue Proteins
-
Sodium Channels