Propentofylline reduces mechanical allodynia and induces mitogen-activated protein kinase phosphatase-1: An experimental study in a rat model of acute incisional pain

ABSTRACT

Background: Acute postoperative pain can lead to long hospital stays, dysfunction, and even chronic pain. Mitogen-activated protein kinases (MAPKs) are important in pain signaling. The activity of MAPKs are negatively regulated by dual specificity phosphatases such as mitogen- activated protein kinase phosphatase-1 (MKP-1), which specifically dephosphorylates MAPK p38. Since, propentofylline (PPF) can reduce pain by inhibiting MAPKs, we hypothesized that PPF relieves acute pain by inducing MKP-1 levels.

Objective: Investigating the anti-nociception effect of an intrathecal injection of PPF in a rat model of acute incisional pain and the role of MKP-1 and phospho-p38 in the mechanism by which PPF ameliorates acute pain.

Methods: We assessed the mechanical withdrawal threshold (MWT) response before and after incisional pain surgery between a control group and a group receiving PPF, and also assessed the effect of pre-treatment with Ro 31–8220, an MKP-1 inhibitor, on PPF effects. Following the MWT, lumbar spinal cord samples were also analyzed by western blot analysis to determine MKP-1 and p-p38 levels.

Results: Following surgery, the MWT response was decreased over 5 h–3 d accompanied by decreased expression of MKP-1 and increased p-p38 levels. An intrathecal injection of PPF increased the MWT response and increased spinal cord MKP-1 expression, but decreased p-p38 levels. Pre-treatment of rats with Ro31-8220 partly reversed the analgesic effect of PPF and its effect on MKP-1/p-p38 levels.

Conclusions: This study suggests that an increase in MKP-1 levels and a corresponding decrease in p-p38 levels may be the mechanism by which PPF ameliorates acute pain.

KEYWORDS:

• Propentofylline
• Ro 31-8220
• neuroglia
• MKP-1
• p-p38
• acute pain

Acknowledgments

We thank Institute of Orthopedics in the second affiliated hospital of Lanzhou University for assistance.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the second affiliated hospital of Lanzhou University under grant [number sdkyjj-14].

Notes on contributors

Yuanyuan Yang

Yuanyuan Yang is an anesthesiologist with a Master degree in the Second Clinical college of Lanzhou University, China. I have several publications in acute pain and also was engaged in labor analgesia.

Yisa Shi

Yisa Shi, chief physician, professor, master's supervisor, Chief expert of Anesthesiology department in Lanzhou University Second Hospital. She was the member of the Tenth and Eleventh Committee of the Anesthesia Branch of the Chinese Medical association and director-designate member of Gansu Medical Association Anesthesiology Committee. She was good at pediatric anesthesia, critically ill patients.

Juan Jia

Juan Jia is an anesthesiologist with a Master degree in the Second Clinical college of Lanzhou University, China. She was engaged in postoperative pain management.

Shenghong Wang

Shenghong Wang is a PhD candidate in the Second Clinical college of Lanzhou University, he has published an article in Journal of Neuroscience inflammation.

Hong Chang

Hong Chang is an urologist in the Second Affiliated Hospital of Lanzhou University with MD in Urology. He was engaged in minimally invasive urology.

Mingguo Li

Mingguo Li is an urologist in the Chinese Medical Hospital of Linyi city with MD in Urology. He was engaged in minimally invasive urology.

Xu Jin

Xu Jin is a member of the communist party of China. He was graduated form Lanzhou University with a master's degree and engaged in anesthesiology and pain management.

Jing Wang

Jing Wang is an orthopedist in the Second Affiliated Hospital of Lanzhou University with PhD degree. She was engaged in pain.