Premium
Opioid inhibition of NMDA‐dependent pain sensitization persists long after the resolution of inflammatory injury
Author(s) -
Corder Gregory,
Doolen Suzanne,
Winter Michelle,
He Ying,
Wang Zaijie,
McCarson Kenneth,
Taylor Bradley
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb836
Subject(s) - nmda receptor , nociception , medicine , opioid , glutamate receptor , agonist , glutamatergic , sensitization , pharmacology , damgo , spinal cord , naltrexone , μ opioid receptor , enkephalin , anesthesia , hyperalgesia , endogenous opioid , endocrinology , receptor , psychiatry , immunology
Endogenous opioids orchestrate an adaptive response that modulates neuronal excitability and fine‐tunes glutamatergic nociceptive transmission. Intraplantar injection of complete Freund's adjuvant (CFA) to C57Bl6 mice decreased mechanical thresholds, which peaked at 3d and resolved within 21d. Upon hypersensitivity resolution, intrathecal injection of mu‐opioid receptor (MOR) blockers, naltrexone (NTX) or CTOP, reinstated mechanical pain and evoked a 3‐fold increase in spinal ERK phosphorylation (pERK). Prior treatment with the NMDA‐R blocker, MK‐801, prevented both NTX‐precipitated pain and pERK. MOR‐G‐protein coupling was assessed by measurement of GTPγ[S35] binding in lumbar spinal cord slices, 21d after sham or CFA injury. Stimulation with the MOR selective agonist DAMGO revealed GTPγ[S35] binding Emax values of 58.02 ± 0.67% or 79.85 ± 7.35% after sham or CFA injection, respectively. Calcium imaging studies in spinal cord slices revealed that either NTX or CTOP potentiated glutamate‐evoked Ca2+ mobilization in CFA but not sham animals. We conclude that NMDA‐Rs drive the spinal sensitization that is masked by up‐regulated, tonically active MORs.