2. Academic Validation
  3. A single dose of ketamine relieves fentanyl-induced-hyperalgesia by reducing inflammation initiated by the TLR4/NF-κB pathway in rat spinal cord neurons

A single dose of ketamine relieves fentanyl-induced-hyperalgesia by reducing inflammation initiated by the TLR4/NF-κB pathway in rat spinal cord neurons

  • Drug Discov Ther. 2023 Aug 9. doi: 10.5582/ddt.2023.01029.
Xin Zhou 1 2,  Qianyi Li 3 4,  Quehua Luo 1 2,  Le Wang 2 5,  Jiaxin Chen 2 6,  Ying Xiong 2,  Guiyun Wu 7,  Lu Chang 2,  Pingping Liu 2 8,  Haihua Shu 1 2 9
Affiliations

Affiliations

  • 1 Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
  • 2 Department of Anesthesiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
  • 3 Guangzhou Kingmylab Pharmaceutical Research Co., Ltd., Guangzhou, Guangdong, China.
  • 4 Guangzhou KingMed Diagnostics Group Co., Ltd., Guangzhou, Guangdong, China.
  • 5 Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 6 School of Medicine South China University of Technology, Guangzhou, Guangdong, China.
  • 7 Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
  • 8 The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
  • 9 The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
PMID: 37558466 DOI: 10.5582/ddt.2023.01029
Abstract

A large amount of clinical evidence has revealed that ketamine can relieve fentanyl-induced hyperalgesia. However, the underlying mechanism is still unclear. In the current study, a single dose of ketamine (5 mg/kg or 10 mg/kg), TAK-242 (3 mg/kg), or saline was intraperitoneally injected into rats 15 min before four subcutaneous injections of fentanyl. Results revealed that pre-administration of ketamine alleviated fentanyl-induced hyperalgesia according to hind paw-pressure and paw-withdrawal tests. High-dose ketamine can reverse the expression of toll-like receptor-dimer (d-TLR4), phospho- nuclear factor kappa-B (p-NF-κB, p-p65), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) 1 d after fentanyl injection in the spinal cord. Moreover, fentany-linduced-hyperalgesia and changes in the expression of the aforementioned proteins can be attenuated by TAK-242, an inhibitor of TLR4, as well as ketamine. Importantly, TLR4, p-p65, COX-2, and IL-1β were expressed in neurons but not in glial cells in the spinal cord 1 d after fentanyl injection. In conclusion, results suggested that a single dose of ketamine can relieve fentanyl-induced-hyperalgesia via the TLR4/NF-κB pathway in spinal cord neurons.

Keywords

COX-2; NF-κB; TLR4; TNF-α; fentanyl; hyperalgesia; ketamine; neuron.

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