Related Experiment Video
Updated: Apr 27, 2026
Electrophysiological Methods to Assess Peripheral Pain Block in an Anesthetized Rat
Published on: November 21, 2025
Selective prevention of mechanical hyperalgesia after incision by spinal ERK1/2 inhibition
I van den Heuvel1, S Reichl, D Segelcke
1Department of General Pediatrics, University Children's Hospital Muenster, Germany.
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.
Insights
Spinal extracellular signal-regulated kinases (ERK1/2) contribute to postsurgical pain, particularly mechanical hyperalgesia. Preventive blockade of ERK1/2 activation is more effective than post-incision treatment for managing incisional pain.
Area of Science:
- Neuroscience
- Pain Research
- Pharmacology
Background:
- Extracellular signal-regulated kinases (ERK1/2) activation is implicated in various pain conditions.
- The role of ERK1/2 in pain following surgical incision requires further investigation.
Purpose of the Study:
- To investigate the contribution of spinal ERK1/2 to non-evoked and evoked pain behaviors in a rat model of surgical incision.
- To assess the efficacy of PD98059, an ERK1/2 inhibitor, in modulating pain signaling and behavior after incision.
Main Methods:
- Assessed spinal ERK1/2 phosphorylation at multiple time points post-incision.
- Administered intrathecal PD98059 pre- or post-incision to evaluate its effects on ERK phosphorylation and pain behaviors.
- Evaluated non-evoked pain, mechanical hyperalgesia, and heat hyperalgesia.
Main Results:
- Surgical incision rapidly increased spinal ERK1/2 phosphorylation.
- Pre-incision administration of PD98059 blocked this increase and delayed mechanical hyperalgesia.
- Post-incision PD98059 showed only a modest effect on mechanical hyperalgesia and did not impact non-evoked or heat hyperalgesia.
Conclusions:
- Spinal ERK1/2 play a differential role in regulating pain modalities after incision.
- Preventive blockade of spinal ERK1/2 is more effective in managing incisional pain than delayed administration.
- Targeting spinal ERK1/2 may offer a future strategy for managing postsurgical, movement-evoked pain.
