Abstract | BACKGROUND: The reduction of γ- aminobutyric acid ( GABA) type A receptor-mediated inhibition has long been implicated in spinal sensitization of nociceptive responses. However, it is largely unknown which signaling cascades in spinal dorsal horn neurons are initiated by the reduced inhibition to trigger pain hypersensitivity. METHODS: GABAergic inhibition was manipulated by intrathecal application of GABA type A receptor antagonist bicuculline in intact mice or by GABA type A receptor agonist muscimol in complete Freund's adjuvant-injected mice. Immunoblotting, coimmunoprecipitation, immunohistochemistry, and behavioral tests were used to explore the signaling pathways downstream of the altered GABAergic tone. RESULTS: CONCLUSION: These data identified STEP61 as a key intermediary for GABAergic inhibition to regulate pain sensitization.
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Authors | Lu Li, Lei Shi, Ying-Ming Xu, Xian Yang, Zhan-Wei Suo, Xiao-Dong Hu |
Journal | Anesthesiology
(Anesthesiology)
Vol. 122
Issue 3
Pg. 686-97
(Mar 2015)
ISSN: 1528-1175 [Electronic] United States |
PMID | 25478941
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- GABA-A Receptor Antagonists
- Receptors, GABA-A
- Protein Tyrosine Phosphatases
- striatal-enriched tyrosine phosphatase 61, mouse
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Topics |
- Animals
- GABA-A Receptor Antagonists
(administration & dosage)
- Male
- Mice
- Mice, Inbred C57BL
- Neural Inhibition
(drug effects, physiology)
- Pain
(drug therapy, metabolism)
- Protein Tyrosine Phosphatases
(biosynthesis)
- Receptors, GABA-A
(physiology)
- Signal Transduction
(drug effects, physiology)
- Spinal Cord Dorsal Horn
(drug effects, metabolism)
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