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 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.
Boucher
T J
TJ
Centre for Neuroscience Research, King's College London, London SE1 7EH, UK.
Okuse
K
K
Bennett
D L
DL
Munson
J B
JB
Wood
J N
JN
McMahon
S B
SB
D000200:Action Potentials / Q000187:drug effects; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D005727:Ganglia, Spinal / Q000503:physiopathology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy*; D008026:Ligation; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy*; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D013127:Spinal Nerves; D014110:Touch
D018712:Analgesics, Non-Narcotic; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D015222:Sodium Channels