Abstract | BACKGROUND: The spinal phosphodiesterase-4 (PDE4) plays an important role in chronic pain. Inhibition of PDE4, an enzyme catalyzing the hydrolysis of cyclic adenosine monophosphate AMP (cAMP), produces potent antinociceptive activity. However, the antinociceptive mechanism remains largely unknown. Connexin43 ( Cx43), a gap junction protein, has been shown to be involved in controlling pain transduction at the spinal level; restoration of Cx43 expression in spinal astrocytes to the normal levels reduces nerve injury-induced pain. Here, we evaluate the novel mechanisms involving spinal cAMP-Cx43 signaling by which PDE4 inhibitors produce antinociceptive activity. METHODS: RESULTS: CONCLUSIONS: The results suggest that the antinociceptive effect of PDE4 inhibitors is contributed by increasing Cx43 expression via cAMP-PKA- cytokine signaling in the spinal dorsal horn.
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Authors | Fang-Fang Zhang, Hao Wang, Yan-Meng Zhou, Hai-Yang Yu, Melanie Zhang, Xian Du, Dong Wang, Feng Zhang, Ying Xu, Ji-Guo Zhang, Han-Ting Zhang |
Journal | CNS neuroscience & therapeutics
(CNS Neurosci Ther)
Vol. 28
Issue 5
Pg. 749-760
(05 2022)
ISSN: 1755-5949 [Electronic] England |
PMID | 35156776
(Publication Type: Journal Article)
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Copyright | © 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. |
Chemical References |
- Connexin 43
- Phosphodiesterase 4 Inhibitors
- Tumor Necrosis Factor-alpha
- Cyclic Nucleotide Phosphodiesterases, Type 4
- Rolipram
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Topics |
- Animals
- Connexin 43
(metabolism)
- Cyclic Nucleotide Phosphodiesterases, Type 4
(metabolism)
- Mice
- Neuralgia
(drug therapy, metabolism)
- Phosphodiesterase 4 Inhibitors
(therapeutic use)
- Rolipram
(therapeutic use)
- Spinal Cord Dorsal Horn
(metabolism)
- Tumor Necrosis Factor-alpha
(metabolism)
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