Linked Life Data

19162071

Source:http://linkedlifedata.com/resource/pubmed/id/19162071

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-4-7
pubmed:abstractText
We discuss and present new data regarding the physiological and molecular mechanisms of nuclear receptor activation in pain control, with a particular emphasis on non-genomic effects of ligands at peroxisome proliferator-activated receptor (PPAR), GPR30, and classical estrogen receptors. PPARalpha agonists rapidly reduce both acute and chronic pain in a number of pain assays. These effects precede transcriptional anti-inflammatory actions, and are mediated in part by IK(ca) and BK(ca) channels on DRG neurons. In contrast to the peripheral site of action of PPARalpha ligands, the dorsal horn supports the expression of PPARgamma. Intrathecal administration of PPARgamma ligands rapidly (< or =5 min) attenuated mechanical and thermal hypersensitivity associated with nerve injury in a dose-dependent manner that could be blocked with PPARgamma antagonists. By contrast, a PPARgamma antagonist itself rapidly increased the mechanical allodynia associated with nerve injury. These data suggest that ligand-dependent, non-genomic activation of spinal PPARgamma decreases behavioral signs of inflammatory and neuropathic pain. We also report that the GPR30 is expressed on cultured sensory neurons, that activation of the receptor elicits signaling to increase calcium accumulation. This signaling may contribute to increased neuronal sensitivity as treatment with the GPR30 agonist induces hyperalgesia. Finally, application of the membrane-impermeable 17beta-E(2)-BSA rapidly (within 15 min) enhanced BK-stimulated inositol phosphate (IP) accumulation and PGE(2)-mediated cAMP accumulation in trigeminal ganglion cultures. We conclude that nuclear receptor ligands may operate through rapid, non-genomic mechanisms to modulate inflammatory and neuropathic pain.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0165-0173
pubmed:author
pubmed:issnType
Print
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
114-24
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Rapid pain modulation with nuclear receptor ligands.
pubmed:affiliation
Department of Endodontics, University of Texas Health Science Center, San Antonio, TX, USA.
pubmed:publicationType
Journal Article, Review, Research Support, N.I.H., Extramural