Linked Life Data

10995854

Source:http://linkedlifedata.com/resource/pubmed/id/10995854

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2000-10-18
pubmed:abstractText
The nonopioid actions of spinal dynorphin may promote aspects of abnormal pain after nerve injury. Mechanistic similarities have been suggested between opioid tolerance and neuropathic pain. Here, the hypothesis that spinal dynorphin might mediate effects of sustained spinal opioids was explored. Possible abnormal pain and spinal antinociceptive tolerance were evaluated after intrathecal administration of [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]enkephalin (DAMGO), an opioid mu agonist. Rats infused with DAMGO, but not saline, demonstrated tactile allodynia and thermal hyperalgesia of the hindpaws (during the DAMGO infusion) and a decrease in antinociceptive potency and efficacy of spinal opioids (tolerance), signs also characteristic of nerve injury. Spinal DAMGO elicited an increase in lumbar dynorphin content and a decrease in the mu receptor immunoreactivity in the spinal dorsal horn, signs also seen in the postnerve-injury state. Intrathecal administration of dynorphin A(1-17) antiserum blocked tactile allodynia and reversed thermal hyperalgesia to above baseline levels (i.e., antinociception). Spinal dynorphin antiserum, but not control serum, also reestablished the antinociceptive potency and efficacy of spinal morphine. Neither dynorphin antiserum nor control serum administration altered baseline non-noxious or noxious thresholds or affected the intrathecal morphine antinociceptive response in saline-infused rats. These data suggest that spinal dynorphin promotes abnormal pain and acts to reduce the antinociceptive efficacy of spinal opioids (i.e., tolerance). The data also identify a possible mechanism for previously unexplained clinical observations and offer a novel approach for the development of strategies that could improve the long-term use of opioids for pain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0270-6474
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7074-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10995854-Analgesics, pubmed-meshheading:10995854-Analgesics, Opioid, pubmed-meshheading:10995854-Animals, pubmed-meshheading:10995854-Drug Tolerance, pubmed-meshheading:10995854-Dynorphins, pubmed-meshheading:10995854-Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, pubmed-meshheading:10995854-Hindlimb, pubmed-meshheading:10995854-Hot Temperature, pubmed-meshheading:10995854-Hyperalgesia, pubmed-meshheading:10995854-Immune Sera, pubmed-meshheading:10995854-Immunohistochemistry, pubmed-meshheading:10995854-Injections, Spinal, pubmed-meshheading:10995854-Male, pubmed-meshheading:10995854-Morphine, pubmed-meshheading:10995854-Pain Measurement, pubmed-meshheading:10995854-Precipitin Tests, pubmed-meshheading:10995854-Rats, pubmed-meshheading:10995854-Rats, Sprague-Dawley, pubmed-meshheading:10995854-Reaction Time, pubmed-meshheading:10995854-Receptors, Opioid, mu, pubmed-meshheading:10995854-Sensory Thresholds, pubmed-meshheading:10995854-Spinal Cord, pubmed-meshheading:10995854-Touch
pubmed:year
2000
pubmed:articleTitle
Dynorphin promotes abnormal pain and spinal opioid antinociceptive tolerance.
pubmed:affiliation
Departments of Pharmacology and Anesthesiology, University of Arizona, Tucson, Arizona 85724, USA.
pubmed:publicationType
Journal Article