Glial cell line-derived neurotrophic factor family ligands enhance capsaicin-stimulated release of calcitonin gene-related peptide from sensory neurons.
The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) are a group of peptides that have been implicated as important factors in inflammation, since they are released in increased amounts during inflammation and induce thermal hyperalgesia upon injection. Mouse isolated sensory neurons in culture and freshly dissociated spinal cord slices were used to examine the enhancement in stimulated-release of the neuropeptide, calcitonin gene-related peptide (CGRP), as a measure of sensitization. Exposure of isolated sensory neurons in culture to GDNF, neurturin, and artemin enhanced the capsaicin-stimulated release of immunoreactive calcitonin gene-related peptide (iCGRP) two- to threefold, but did not increase potassium-stimulated release of iCGRP. A similar profile of sensitization was observed in freshly dissociated spinal cord slices. Persephin, another member of the GFL family thought to be important in development, was unable to induce an enhancement in the release of iCGRP. These results demonstrate that specific GFLs are important mediators affecting sensory neuronal sensitivity, likely through modulation of the capsaicin receptor. The sensitization of sensory neurons during inflammation, and the pain and neurogenic inflammation resulting from this sensitization, may be due in part to the effects of these selected GFLs.
Schmutzler
B S
BS
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Stark Neurosciences Research Institute, 950 West Walnut Street, Research Building 2, Room 444, Indianapolis, IN 46202, USA. bschmutz@iupui.edu
Roy
S
S
Hingtgen
C M
CM
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D002478:Cells, Cultured; D051098:Glial Cell Line-Derived Neurotrophic Factors / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism
D051098:Glial Cell Line-Derived Neurotrophic Factors; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin