2. Academic Validation
  3. Upregulation of the oxytocin receptors on peripheral sensory neurons mediated analgesia in chemotherapy-induced neuropathic pain

Upregulation of the oxytocin receptors on peripheral sensory neurons mediated analgesia in chemotherapy-induced neuropathic pain

  • Br J Pharmacol. 2023 Jan 26. doi: 10.1111/bph.16042.
Lixuan Li 1 2,  Pupu Li 3,  Jing Guo 4,  Yifei Wu 5,  Qian Zeng 2,  Nan Li 2,  Xiaoting Huang 6,  Yongshen He 6,  Wen Ai 6,  Wuping Sun 2,  Tao Liu 7,  Donglin Xiong 2,  Lizu Xiao 2,  Yanyan Sun 8,  Qiming Zhou 3,  Haixia Kuang 7,  Zilong Wang 5,  Changyu Jiang 2 6
Affiliations

Affiliations

  • 1 Guangdong Medical University, Zhanjiang, Guangdong, 524023, China.
  • 2 Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, The 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, Guangdong, 518052, China.
  • 3 Department of Medical Oncology, The 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, Guangdong, 518052, China.
  • 4 Department of Endocrinology and Metabolism, Shenzhen University General Hospital and Shenzhen University Academy of Clinical Medical Sciences, Shenzhen University, Shenzhen, Guangdong, 518052, China.
  • 5 Department of Medical Neuroscience, Key University Laboratory of Metabolism and Health of Guangdong, SUSTech Center for Pain Medicine, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, 518052, China.
  • 6 Medical Research Center, The 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, Guangdong, 518052, China.
  • 7 Department of Pediatrics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330000, China.
  • 8 Department of Anesthesiology, Shenzhen University General Hospital and Shenzhen University Academy of Clinical Medical Sciences, Shenzhen University, Shenzhen, Guangdong, 518052, China.
PMID: 36702458 DOI: 10.1111/bph.16042
Abstract

Background and purpose: Currently, chemotherapy-induced neuropathic pain (CINP) has limited effective treatment. The roles of Oxytocin (OXT) and the Oxytocin Receptor (OXTR) in central analgesia have been well documented. However, the expression and function of OXTR in the peripheral nervous system remain unclear. Here, we evaluated the peripheral antinociceptive profiles of OXTR in CINP.

Experimental approach: Paclitaxel (PTX) was used to establish CINP. qRT-PCR, in-situ hybridization, and immunohistochemistry were used to observe the properties of OXTR expression in the dorsal root ganglion (DRG). The antinociceptive effects were assessed by the hot-plate and Von-Frey tests. The whole-cell patch-clamp was performed to record the sodium currents, the excitability of DRG neurons, and the excitatory synapse transmissions.

Key results: The expression of OXTR in DRG neurons was boosted significantly after PTX treatment. The activation of OXTR exhibited antinociceptive effects and decreased the hyperexcitability of DRG neurons in PTX-treated mice. Additionally, the OXTR activation upregulated the phosphorylation of protein kinase C (pPKC), and in turn impaired the voltage-gated sodium current, especially Nav 1.7 current which performs an indispensable role in PTX-induced neuropathic pain. Oxytocin also suppressed the excitatory transmission in the spinal dorsal horn and the excitatory inputs from the primary afferents in PTX-treated mice.

Conclusion and implications: The OXTR in small-sized DRG neurons is upregulated in CINP and the activation of OXTR relieved CINP by inhibiting the neural excitability by an impairment in NaV 1.7 currents via pPKC. Our results suggested that OXTR on peripheral sensory neurons can be a potential target to relieve CINP.

Keywords

chemotherapy-induced peripheral neuropathic pain; oxytocin; oxytocin receptor; paclitaxel.

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