WESTPORT, CT (Reuters Health) Oct 6 - Glial cell line-derived neurotrophic factor (GDNF) treatment reverses sensory abnormalities in a rat model of neuropathic pain, according to a report in the October 6th issue of Science.
Timothy Boucher from King's College London, UK and colleagues examined the ability of GDNF to influence neuropathic pain, and investigated its mechanism of action, in rats with partial ligation of one sciatic nerve.
Animals treated with GDNF by continuous intrathecal infusion at the time of nerve ligation developed neither mechanical nor thermal hyperalgesia, the authors report, unlike vehicle-treated animals. Similarly, GDNF treatment beginning after neuropathic symptoms had already developed reversed the hyperalgesia, the researchers note. Hyperalgesia returned within 3 days after discontinuation of GDNF.
GDNF administered to normal animals did not influence their responses to noxious thermal or mechanical stimuli, the report indicates.
GDNF appeared to work by reducing the number of damaged myelinated sensory fibers that exhibited spontaneous discharges, the investigators observe, most likely by reversing the injury-induced changes in several sodium channel subunits.
"Together these findings provide a rational basis for the use of GDNF as a therapeutic treatment for neuropathic pain states," the authors conclude.
Stephen McMahon, also at King's College London and a co-author of the report, commented to Reuters Health, "We observed that when we discontinued treatment after several weeks, neuropathic pain re-emerged. This suggests that long-term treatment would be necessary with GDNF (or an agonist)." Nonetheless, "This new knowledge offers a range of novel targets for drug development."