Linked Life Data

20237269

Source:http://linkedlifedata.com/resource/pubmed/id/20237269

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-3-18
pubmed:abstractText
Small unmyelinated sensory neurons classified as nociceptors are divided into two subpopulations based on phenotypic differences, including expression of neurotrophic factor receptors. Approximately half of unmyelinated nociceptors express the NGF receptor TrkA, and half express the GDNF family ligand (GFL) receptor Ret. The function of NGF/TrkA signaling in the TrkA population of nociceptors has been extensively studied, and NGF/TrkA signaling is a well established mediator of pain. The GFLs are analgesic in models of neuropathic pain emphasizing the importance of understanding the physiological function of GFL/Ret signaling in nociceptors. However, perinatal lethality of Ret-null mice has precluded the study of the physiological role of GFL/Ret signaling in the survival, maintenance, and function of nociceptors in viable mice. We deleted Ret exclusively in nociceptors by crossing nociceptor-specific Na(v)1.8 Cre and Ret conditional mice to produce Ret-Na(v)1.8 conditional knock-out (CKO) mice. Loss of Ret exclusively in nociceptors results in a reduction in nociceptor number and size, indicating that Ret signaling is important for the survival and trophic support of these cells. Ret-Na(v)1.8 CKO mice exhibit reduced epidermal innervation but normal central projections. In addition, Ret-Na(v)1.8 CKO mice have increased sensitivity to cold and increased formalin-induced pain, demonstrating that Ret signaling modulates the function of nociceptors in vivo. Enhanced inflammation-induced pain may be mediated by decreased prostatic acid phosphatase (PAP), as PAP levels are markedly reduced in Ret-Na(v)1.8 CKO mice. The results of this study identify the physiological role of endogenous Ret signaling in the survival and function of nociceptors.
pubmed:grant
http://linkedlifedata.com/resource/pubmed/grant/, http://linkedlifedata.com/resource/pubmed/grant/AGO13730, http://linkedlifedata.com/resource/pubmed/grant/DK081644, http://linkedlifedata.com/resource/pubmed/grant/DK082531, http://linkedlifedata.com/resource/pubmed/grant/HD047396, http://linkedlifedata.com/resource/pubmed/grant/K08 HD047396-01, http://linkedlifedata.com/resource/pubmed/grant/NS042595, http://linkedlifedata.com/resource/pubmed/grant/P30 DK079333-01, http://linkedlifedata.com/resource/pubmed/grant/P30 NS057105, http://linkedlifedata.com/resource/pubmed/grant/P30 NS057105-01, http://linkedlifedata.com/resource/pubmed/grant/P30-DK079333, http://linkedlifedata.com/resource/pubmed/grant/R01 AG013730-04, http://linkedlifedata.com/resource/pubmed/grant/R01 DK081644-01A1, http://linkedlifedata.com/resource/pubmed/grant/R01 DK081644-03, http://linkedlifedata.com/resource/pubmed/grant/R01 DK082531-01, http://linkedlifedata.com/resource/pubmed/grant/R01 NS042595-06A1, http://linkedlifedata.com/resource/pubmed/grant/R21 NS059566-01, http://linkedlifedata.com/resource/pubmed/grant/R21NS059566
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3983-94
pubmed:dateRevised
2011-8-10
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
RET signaling is required for survival and normal function of nonpeptidergic nociceptors.
pubmed:affiliation
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. jgolden@wustl.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural