2. Academic Validation
  3. Intracellular metabotropic glutamate receptor 5 in spinal dorsal horn neurons contributes to pain in a mouse model of vincristine-induced neuropathic pain

Intracellular metabotropic glutamate receptor 5 in spinal dorsal horn neurons contributes to pain in a mouse model of vincristine-induced neuropathic pain

  • Neurosci Lett. 2025 Mar 15:852:138193. doi: 10.1016/j.neulet.2025.138193.
Xiao Li 1,  Hui Yang 2,  Ming Qian 2,  Hang Liu 2,  Shuang Zuo 1,  Jin-Chun Liu 3,  Wei-Hong Ge 4,  Lin Zhou 5
Affiliations

Affiliations

  • 1 Affiliated Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing 210008 Jiangsu, China.
  • 2 Department of Pharmacy, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008 Jiangsu, China.
  • 3 Department of Pharmacy, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008 Jiangsu, China. Electronic address: liujinchun@njglyy.com.
  • 4 Affiliated Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing 210008 Jiangsu, China; Department of Pharmacy, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008 Jiangsu, China. Electronic address: weihonggetower@sina.com.
  • 5 Department of Pharmacy, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008 Jiangsu, China. Electronic address: linzhoucpu@163.com.
PMID: 40074023 DOI: 10.1016/j.neulet.2025.138193
Abstract

Vincristine (VCR) is a commonly used clinical anti-cancer drug, but it can also induce neurotoxicity and cause vincristine-induced neuropathic pain (VINP). The metabotropic glutamate receptor 5 (mGluR5) within spinal dorsal horn neurons regulates the transmission of pain mediated by glutamate. In this study, we investigated for the first time the role of mGluR5 in the transmission of noxious information in VINP. Expression of mGluR5 protein was significantly increased in the spinal cord from days 6 to 14 after VCR injection. Immunofluorescence double staining showed that mGluR5 colocalized with the neuron-specific marker NeuN. The intrathecal administration of MPEP (a specific antagonist of mGluR5) or DHPG (an agonist of mGluR5) influenced the pain threshold and mGluR5 protein expression in VINP mice. The expression of c-Fos protein was also affected by MPEP. Furthermore, simulated blockade of intracellular mGluR5 site by intrathecal injection of small interfering RNA (siRNA) of the excitatory amino acid transporter 3 (EAAT3) reduced mechanical allodynia and thermal hyperalgesia and suppressed the expression of mGluR5 and c-Fos proteins. The results collectively indicate that mGluR5 site in spinal dorsal horn neurons may be involved in the regulation of intracellular nociceptive signal transmission in VINP, and the expression of c-Fos largely depends on the intracellular mGluR5.

Keywords

Neuron; Neuropathic pain; Spinal dorsal horn; Vincristine; mGluR5.

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