Abstract | BACKGROUND: METHODS: Spinal phosphorylation of ERK1 and ERK2 was assessed 15 min, 4 h, 24 h and 5 days after plantar incision and sham incision. The effect of PD98059, a specific inhibitor of ERK1/2 activation, administered intrathecally (IT) 1 h before or 2 h after incision on spinal ERK1 and ERK2 phosphorylation was assessed. In behavioural experiments, the effect of PD98059 administered 1 h before or after incision on non-evoked pain behaviour and mechanical and heat hyperalgesia was assessed. RESULTS: Phosphorylated ERK1 and ERK2 were rapidly increased in the ipsilateral dorsal horn from rats after incision post-operatively. This increased ERK1 and ERK2 phosphorylation were blocked by PD98059 administered before incision. In congruence, IT administration of PD98059 before incision delayed mechanical hyperalgesia after incision; however, administration after incision had only a modest effect on mechanical hyperalgesia. In addition, PD98059 did not affect non-evoked pain behaviour or heat hyperalgesia after incision. CONCLUSION: The results suggest that spinal ERK1 and ERK2 are involved in regulation of pain after incision differentially with regard to the pain modality. Furthermore, blockade of ERK1/2 activation was most effective in a preventive manner, a condition which is rare after incision. Spinal ERK1/2 inhibition could therefore be a very useful tool to manage selectively movement-evoked pain after surgery in the future.
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Authors | I van den Heuvel, S Reichl, D Segelcke, P K Zahn, E M Pogatzki-Zahn |
Journal | European journal of pain (London, England)
(Eur J Pain)
Vol. 19
Issue 2
Pg. 225-35
(Feb 2015)
ISSN: 1532-2149 [Electronic] England |
PMID | 24976579
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 European Pain Federation - EFIC® |
Chemical References |
- Flavonoids
- Protein Kinase Inhibitors
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Topics |
- Animals
- Flavonoids
(pharmacology)
- Hyperalgesia
(prevention & control)
- MAP Kinase Signaling System
(drug effects)
- Male
- Mitogen-Activated Protein Kinase 1
(antagonists & inhibitors)
- Mitogen-Activated Protein Kinase 3
(antagonists & inhibitors)
- Pain
(metabolism)
- Pain Measurement
(methods)
- Pain, Postoperative
(metabolism)
- Protein Kinase Inhibitors
(pharmacology)
- Rats, Sprague-Dawley
- Spinal Cord
(metabolism)
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