β-Elemene Improves Morphine Tolerance in Bone Cancer Pain via N-Methyl-D-Aspartate Receptor 2B Subunit-Mediated μ-Opioid Receptor

Abstract

Background Improving morphine tolerance (MT) is an urgent problem in the clinical treatment of bone cancer pain. Considering that β -Elemene is widely used in the treatment of cancer pain, we explored the effects and mechanism of β -Elemene in preventing MT of bone cancer pain. Method Bone cancer pain and chronic MT rat model was established by injecting MADB106 cells and morphine (10 mg/kg). SH-SY5Y cells were treated with morphine (10 μ g/mL) for 48 h to establish a cell model. The mechanical withdrawal threshold and thermal withdrawal latency of rats were detected by mechanical allodynia and thermal hyperalgesia tests, respectively. The protein expressions of μ -opioid receptor (MOPR), cyclic adenosine monophosphate (cAMP), N-methyl-D-aspartate receptor subunit 2B (NR2B), phosphorylated-calmodulin-dependent protein kinase II (p-CaMKII), and CaMKII were detected by western blot. The viability of SH-SY5Y cells was determined by the cell counting kit-8 assay. cAMP content in SH-SY5Y cells was measured by a LANCE cAMP kit. Result Animal experiments showed that MT strengthened over time, while increased β -Elemene dosage alleviated MT. The viability of SH-SY5Y cells was down-regulated by high-dose β -Elemene. In the rat and cell models, long-term morphine treatment decreased the expression of MOPR and increased the cAMP and NR2B expressions and p-CaMKII/CaMKII, while β -Elemene and siNR2B counteracted the effects of morphine treatment. In addition, siNR2B reversed the effects of β -Elemene on related protein expressions and cAMP content in the cell model. Conclusion β -Elemene improved MT in bone cancer pain through the regulation of NR2B-mediated MOPR.

Retracted: β‐Elemene Improves Morphine Tolerance in Bone Cancer Pain via N‐Methyl‐D‐Aspartate Receptor 2B Subunit‐Mediated μ‐Opioid Receptor

“…This article has been retracted by Hindawi, as publisher, following an investigation undertaken by the publisher [1]. This investigation has uncovered evidence of systematic manipulation of the publication and peer-review process.…”