Role of spinal cyclooxygenase-2 and prostaglandin E2 in fentanyl-induced hyperalgesia in rats.

Abstract

BACKGROUND:

Accumulated evidence suggests that spinal cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) may be implicated in the development of opioid-induced hyperalgesia.

METHODS:

Rats received subcutaneous fentanyl injections at different doses (20-80 μg kg-1), four separate times at 15-min intervals. Some rats only received fentanyl (60 μg kg-1 × 4 doses) with or without surgical incision. Fentanyl-induced hyperalgesia was evaluated via a tail-pressure or paw-withdrawal test. The concentrations of spinal COX-2, EP-1 receptor (EP-1R) mRNA, and PGE2 were measured. The effects of the COX-2 inhibitor, parecoxib (intraperitoneal 10 mg kg-1), or the EP-1R antagonist, SC51089 (intraperitoneal 100 μg kg-1), on hyperalgesia and spinal PGE2 were examined.

RESULTS:

Acute repeated injections of fentanyl dose-dependently induced mechanical hyperalgesia, which reached a peak at the 1st day and persisted for 1-4 days postinjection. This hyperalgesia could be partly or totally prevented by the pretreatment of either parecoxib or SC51089. Consistently, the levels of spinal COX-2 mRNA and PGE2 were also dose-dependently increased, reaching a peak at the first day and persisting for 2 days postinjection. Pretreatment with parecoxib could block the increase in spinal PGE2 and had no effects on spinal COX-2 and EP-1R mRNA. Fentanyl injection enhanced incision-induced mechanical and thermal hyperalgesia.

CONCLUSIONS:

Acute repeated fentanyl administration dose-dependently produced mechanical hyperalgesia and augmented surgery induced postoperative hyperalgesia. This behavioural change was paralleled with an increase in spinal COX-2 mRNA and PGE2 after fentanyl administration. Inhibition of COX-2 or blockade of EP-1R can partly or totally prevent hyperalgesia.

• Authors: Q B Li, L Chang, F Ye, Q H Luo, Y X Tao, H H Shu
• Journal: British journal of anaesthesia (Br J Anaesth) Vol. 120 Issue 4 Pg. 827-835 (Apr 2018) ISSN: 1471-6771 [Electronic] England
• PMID: 29576123 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 British Journal of Anaesthesia. All rights reserved.

Chemical References

• Analgesics, Opioid
• Cyclooxygenase 2
• Dinoprostone
• Fentanyl

Topics

• Analgesics, Opioid (administration & dosage)
• Animals
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Fentanyl (administration & dosage)
• Hyperalgesia (metabolism)
• Male
• Rats
• Rats, Sprague-Dawley
• Spinal Cord (metabolism)