Abstract | BACKGROUND: METHODS: Real-time polymerase chain reaction was performed to determine interleukin-1β (IL-1β), IL-6 and tumour necrosis factor-α (TNF-α) mRNAs in the spinal dorsal horn and cultured sensory ganglion explants. Immunohistochemistry was performed to identify spinal microglia and astrocytes. RESULTS: Repetitive intrathecal (i.t.) injection of morphine (20 μg) increased the expression of IL-1β, IL-6 and TNF-α mRNAs in the spinal dorsal horn. The co-administration of the selective AM receptor antagonist AM22-52 (36 μg) markedly attenuated chronic morphine-evoked increase in IL-1β and IL-6, but not TNF-α, mRNA levels. Exposure of cultured dorsal root ganglion (DRG) explants to morphine (3.3 μmol/L) for 6 days up-regulated IL-1β and IL-6 mRNA expressions. The depletion of AM gene using small interfering RNA ( siRNA) approach abolished morphine-evoked increase in IL-1β and IL-6 syntheses in the cultured DRG. The blockade of AM receptors by i.t. AM22-52 also inhibited chronic morphine-evoked cell hypertrophy of microglia and astrocytes as well as an increase in OX-42 and GFAP ( glial fibrillary acidic protein) immunoreactivities. Furthermore, the 6-day treatment with AM (10 μg, i.t.) induced morphological changes of microglia and astrocytes as well as an increase in IL-1β, IL-6 and TNF-α mRNA levels in the spinal dorsal horn. CONCLUSION: The present study supports the idea that up-regulation of the pronociceptive mediator AM can recruit spinal glial cells, resulting in an increase in cytokines during chronic use of morphine.
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Authors | X Zeng, M Y Lin, D Wang, Y Zhang, Y Hong |
Journal | European journal of pain (London, England)
(Eur J Pain)
Vol. 18
Issue 9
Pg. 1323-32
(Oct 2014)
ISSN: 1532-2149 [Electronic] England |
PMID | 24664661
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 European Pain Federation - EFIC® |
Chemical References |
- Cytokines
- Narcotics
- Adrenomedullin
- Morphine
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Topics |
- Adrenomedullin
(administration & dosage, metabolism, pharmacology)
- Animals
- Cytokines
(metabolism)
- Gliosis
(chemically induced, metabolism)
- Male
- Morphine
(administration & dosage, pharmacology)
- Narcotics
(administration & dosage, pharmacology)
- Rats
- Rats, Sprague-Dawley
- Spinal Cord Dorsal Horn
(drug effects, metabolism)
- Up-Regulation
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