Linked Life Data

19167016

Source:http://linkedlifedata.com/resource/pubmed/id/19167016

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2009-3-3
pubmed:abstractText
Opioids are an effective treatment for the signs and symptoms of Restless Legs Syndrome (RLS) and the signs and symptoms of RLS return when the opiate receptor blocker naloxone is given to opioid treated RLS patients in a blinded fashion. These data suggest that the opioid effect is specific to the opiate receptor in RLS and implicate the endogenous opioid system with its enkephalins and endorphins in the pathogenesis of RLS. We therefore measured Beta endorphin, Met-enkephalin and Leu-enkephalin levels in thalamus and substantia nigra of RLS patients (5 F - avg age 80.2 years) compared to controls (5 F, 1 M - avg age 76.3 years). One half of each brain was fixed in paraformaldehyde (PFA) in phosphate buffered saline (PBS) for pathologic evaluation and paraffin sections were stained with antibodies. Cell numbers were counted in a blinded fashion. In the thalamus, there were reductions of Beta-endorphin and Met-enkephalin positive cells by 37.5% (p=.006, effect size 2.16) and 26.4% (p=.028, effect size 1.58), respectively, in RLS patients compared to controls. There was no difference in Leu-enkephalin in the thalamus or changes in Beta endorphin, Met-enkephalin, Leu-enkephalin or Tyrosine Hydroxylase, the rate limiting step for dopamine synthesis, in the substantia nigra. Although one of the main hypotheses for pathogenesis has been that there is a dopaminergic hypofunction in RLS, this lack of decrease in Tyrosine Hydroxylase in substantia nigra is consistent with previously published post-mortem data in RLS. With Bonferroni correction, the decrease in thalamic Beta endorphin remained significant (p= .006 x 7= .042). These results suggest that there may be altered central processing of pain in RLS and these data further implicate the endogenous opioid system in the pathogenesis of RLS. The mu opiate receptor subtype may be involved in the pathogenesis of RLS as it is the target of Beta-endorphin and Met-enkephalin but not Leu-enkephalin. However, these results should be viewed as only preliminary and more advanced techniques such as stereology should be employed in future post-mortem studies. In addition, other opioid rich areas need to be explored as well as areas implicated in the pathogenesis of RLS such as the red nucleus and raphe nucleus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1878-5883
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
62-5
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Does the endogenous opiate system play a role in the Restless Legs Syndrome? A pilot post-mortem study.
pubmed:affiliation
Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232-2551, USA. Arthur.Walters@Vanderbilt.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't