COX-2 contributed to the remifentanil-induced hyperalgesia related to ephrinB/EphB signaling

ABSTRACT

Background and Objectives： Studying the underlying mechanisms of opiate-induced hyperalgesia is fundamental to understanding and treating pain. Our previous study has proved that ephrinB/EphB signaling contributes to opiate-induced hyperagesia, but the manner in which ephrinB/EphB signaling acts on spinal nociceptive information networks to produce hyperalgesia remains unclear. Other studies have suggested that ephrinB/EphB signaling, NMDA receptor and COX-2 act together to participate in the modulation of nociceptive information processes at the spinal level. The objective of this research was to investigate the role of COX-2 in remifentanil-induced hyperalgesia and its relationship with ephrinB/EphB signaling.

Methods： We characterized the remifentanil-induced pain behaviours by evaluating thermal hyperalgesia and mechanical allodynia in a mouse hind paw incisional model. Protein expression of COX-2 in spinal cord was assayed by western blotting and mRNA level of COX-2 was assayed by Real-time PCR (RT-PCR).

Results： Continuing infusion of remifentanil produced thermal hyperalgesia and mechanical allodynia, which was accompanied by increased expression of spinal COX-2 protein and mRNA. This response was inhibited by pre-treatment with EphB2-Fc, an antagonist of ephrinB/EphB. SC58125 and NS398, inhibitors of COX-2, suppressed pain behaviours induced by remifentanil infusion and reversed the increased pain behaviours induced by intrathecal injection of ephrinB2-Fc, an agonist of ephrinB/EphB.

Conclusions: Our findings confirmed that COX-2 is involved in remifentanil-induced hyperalgesia related to ephrinB/EphB signaling. EphrinB/EphB signaling might be the upstream of COX-2.

KEYWORDS:

• COX-2
• ephrinB/EphB signaling
• remifentanil-induced hyperalgesia

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Grant No. 81701101] .

Notes on contributors

Yunan Peng

Yunan Peng, graduated from Zhejiang University of China with a master's degree. The major research direction is pain.

Ting Zang

Ting Zang, graduated from Xuzhou Medical University of China with a master's degree. The major research direction is epigenetics and pain.

Luyang Zhou

Luyang Zhou, graduated from Nanjing University of China with a master's degree. The major research direction is perioperative medicine.

Kun Ni

Kun Ni, graduated from Nanjing University of China with a master's degree. The major research direction is pain.

Xuelong Zhou

Xuelong Zhou, graduated from Zhejiang University of China with a Ph.D. The major research direction is pain.