Arizona Health Sciences

Repeated morphine treatment-mediated hyperalgesia, allodynia and spinal glial activation are blocked by co-administration of a selective cannabinoid receptor type-2 agonist.

TitleRepeated morphine treatment-mediated hyperalgesia, allodynia and spinal glial activation are blocked by co-administration of a selective cannabinoid receptor type-2 agonist.
Publication TypeJournal Article
Year of Publication2012
AuthorsTumati S, Largent-Milnes TM, Keresztes A, Ren J, Roeske WR, Vanderah TW, Varga EV
JournalJ Neuroimmunol
Volume244
Issue1-2
Pagination23-31
Date Published2012 Mar
ISSN1872-8421
KeywordsAnalgesics, Analgesics, Opioid, Animals, Cannabinoids, Hyperalgesia, Indoles, Inflammation, Interleukin-1beta, Male, Morphine, Neuroglia, Pain, Piperidines, Pyrazoles, Rats, Rats, Sprague-Dawley, Receptor, Cannabinoid, CB2, Spinal Cord, Tumor Necrosis Factor-alpha
Abstract

Spinal glial activation has been implicated in sustained morphine-mediated paradoxical pain sensitization. Since activation of glial CB2 cannabinoid receptors attenuates spinal glial activation in neuropathies, we hypothesized that CB2 agonists may also attenuate sustained morphine-mediated spinal glial activation and pain sensitization. Our data indicate that co-administration of a CB2-selective agonist (AM 1241) attenuates morphine (intraperitoneal; twice daily; 6 days)-mediated thermal hyperalgesia and tactile allodynia in rats. A CB2 (AM 630) but not a CB1 (AM 251) antagonist mitigated this effect. AM 1241 co-treatment also attenuated spinal astrocyte and microglial marker and pro-inflammatory mediator (IL-1β, TNFα) immunoreactivities in morphine-treated rats, suggesting that CB2 agonists may be useful to prevent the neuroinflammatory consequences of sustained morphine treatment.

DOI10.1016/j.jneuroim.2011.12.021
Alternate JournalJ. Neuroimmunol.
PubMed ID22285397
PubMed Central IDPMC3298577
Grant ListDA006284 / DA / NIDA NIH HHS / United States
DA027786 / DA / NIDA NIH HHS / United States
P01 DA006284 / DA / NIDA NIH HHS / United States
P01 DA006284-04 / DA / NIDA NIH HHS / United States
R01 DA013449 / DA / NIDA NIH HHS / United States
R01 DA013449-02 / DA / NIDA NIH HHS / United States
R21 DA027786-01 / DA / NIDA NIH HHS / United States
R21 DA027786-02 / DA / NIDA NIH HHS / United States
Faculty Member Reference: 
Tally Largent-Milnes, Ph.D.
William R. Roeske, MD
Todd Vanderah, PhD
Eva Varga, Ph.D.