Modulation of neuropathic pain by a glial-derived factor.
BACKGROUND
An unfortunate consequence of incomplete nerve injury is development of neuropathic pain and associated allodynia, a feeling of discomfort in response to benign stimuli. Nerve injuries induce alterations in cytokine expression by Schwann cells, locally at the site of injury, and by glia, remotely in the spinal cord. Although most cytokines are pronociceptive, one, glial cell line-derived neurotrophic factor (GDNF), appears to be antinociceptive.


METHODS
We have developed a novel method of delivering GDNF to the site of nerve injury. Using a model of partial nerve injury that reduces withdrawal thresholds to innocuous stimuli, we have found that local application of GDNF abolishes this allodynic behavior.


RESULTS
Intrathecal application of GDNF stimulates expression of somatostatin, a neuropeptide with potential analgesic properties. Moreover, stimulation of dorsal root sensory neurons with GDNF in vitro increases cell content of somatostatin, which, in turn, leads to increased secretion in response to depolarizing stimuli.


CONCLUSIONS
We suggest that GDNF exerts its anti-allodynic effect via somatostatinergic mechanisms. Our observations suggest new approaches for treating nerve injury that may prove useful in preventing delayed complications that contribute to long-term debility.
Adler
Joshua E
JE
Department of Neurology, John Dingell Veterans Administration Medical Center, Detroit, MI 48201, USA. Joshua.Adler@va.gov
Nico
Lindsey
L
VandeVord
Pamela
P
Skoff
Anne M
AM
D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage*; D007278:Injections, Spinal / Q000379:methods; D009437:Neuralgia / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D000700:Analgesics; D003692:Delayed-Action Preparations; D051100:Glial Cell Line-Derived Neurotrophic Factor