Potent Analgesic Effects of GDNF in Neuropathic Pain States

• Published in: Science (American Association for the Advancement of Science) Vol. 290; no. 5489; pp. 124 - 127
• Main Authors: Boucher, Timothy J., Okuse, Kenji, David L. H. Bennett, Munson, John B., Wood, John N., McMahon, Stephen B.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 06.10.2000; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Action Potentials - drug effects; Analgesics; Analgesics, Non-Narcotic - pharmacology; Analgesics, Non-Narcotic - therapeutic use; Analysis; Animals; Biochemistry; Biological and medical sciences; Etiology; Ganglia, Spinal - physiopathology; Glial Cell Line-Derived Neurotrophic Factor; Hot Temperature; Hyperalgesia; Hyperalgesia - drug therapy; Injuries; Ligation; Medical sciences; 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; Nervous system; Neural Conduction - drug effects; Neurology; Neurons; Neurons, Afferent - drug effects; Neurons, Afferent - physiology; Neuropharmacology; Pain; Pain - drug therapy; Pain Threshold - drug effects; Peripheral nervous system diseases; Peripheral Nervous System Diseases - physiopathology; Pharmacology. Drug treatments; Rats; rev genes; Reverse Transcriptase Polymerase Chain Reaction; Sciatic Nerve; Sensory neurons; Sodium Channels - genetics; Sodium Channels - metabolism; Spinal Nerves; Statistical Analysis; Stimuli; T lymphocytes; Touch; Transcripts (Written Records); Wave functions; United Kingdom; Nervous system diseases; Vertebrata; Chemotherapy; Mammalia; Analgesic; Pain; Treatment; Rat; Animal; Rodentia; Glial cell line derived neurotrophic factor; Neuropathy
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.290.5489.124

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.