Dexmedetomidine Alleviates Remifentanil-Induced Hyperalgesia in Rats by Modulating the P2 X 4/BDNF Pathway

Abstract

In the clinical settings, patients often develop opioid-induced hyperalgesia (OIH) after utilization of high dose intra-operative remifentanil. It is widely considered that systemic α₂ agonists, including dexmedetomidine (DEX), have the potential to mitigate postoperative pain and minimize the needs for opioid, thus leading to a decrease in the incidence of hyperalgesia. However, the regulating method remains ambiguous. Recent studies have shown that DEX can alleviate spinal nerve injury via regulating P2 X 4. Although the effects of DEX on remifentanil-induced hyperalgesia (RIH) have been previously reported, the specific mechanisms remain to be fully elucidated. The objective of our study was to investigate the potential of intraperitoneal injections of DEX in attenuate RIH in rats through the modulation of P2 X 4Rs and brain-derived neurotrophic factor (BDNF) in spinal cord. The findings of this study indicate that intraperitoneal administration of DEX at a dosage of 50 µg/kg could alleviate mechanical allodynia and thermal hyperalgesia, as demonstrated through a behavioral test. Moreover, DEX suppressed the enhancement of P2 X 4 and BDNF expression induced by RIH. Furthermore, the structure of synaptic clefts caused by RIH showed improvement to a certain extent after DEX treatment, as shown using TEM transmission electron microscopy. In summary, we examined the protective effect of DEX on remifentanil-induced hyperalgesia. The findings indicates that the reduced expression of P2 X 4 and decreased synthesis and release of BDNF may be responsible for the analgesic processes. This study would provide a new perspective and strategy for the pharmacological treatment on RIH.