Selective prevention of mechanical hyperalgesia after incision by spinal ERK1/2 inhibition.

Abstract

BACKGROUND:

Activation of extracellular signal-regulated kinases (ERK1/2) has been shown to play an important role in several pain states. Here we investigated the ERK1/2 contribution to non-evoked and evoked pain-like behaviour in rats after surgical incision.

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.

• 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)
• 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

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)