Bone cancer-induced pain is associated with glutamate signalling in peripheral sensory neurons Journal Articles uri icon

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  • We previously identified that several cancer cell lines known to induce nociception in mouse models release glutamate in vitro. Although the mechanisms of glutamatergic signalling have been characterized primarily in the central nervous system, its importance in the peripheral nervous system has been recognized in various pathologies, including cancer pain. We therefore investigated the effect of glutamate on intracellular electrophysiological characteristics of peripheral sensory neurons in an immunocompetent rat model of cancer-induced pain based on surgical implantation of mammary rat metastasis tumour-1 cells into the distal epiphysis of the right femur. Behavioural evidence of nociception was detected using von Frey tactile assessment. Activity of sensory neurons was measured by intracellular electrophysiological recordings in vivo. Glutamate receptor expression at the mRNA level in relevant dorsal root ganglia was determined by reverse transcription polymerase chain reaction using rat-specific primers. Nociceptive and non-nociceptive mechanoreceptor neurons exhibiting changes in neural firing patterns associated with increased nociception due to the presence of a bone tumour rapidly responded to sulphasalazine injection, an agent that pharmacologically blocks non-vesicular glutamate release by inhibiting the activity of the system xC− antiporter. In addition, both types of mechanoreceptor neurons demonstrated excitation in response to intramuscular glutamate injection near the femoral head, which corresponds to the location of cancer cell injection to induce the bone cancer-induced pain model. Therefore, glutamatergic signalling contributes to cancer pain and may be a factor in peripheral sensitization and induced tactile hypersensitivity associated with bone cancer-induced pain.


  • Zhu, Yong Fang
  • Linher-Melville, Katja
  • Wu, Jianhan
  • Fazzari, Jennifer
  • Miladinovic, Tanya
  • Ungard, Robert
  • Zhu, Kan Lun
  • Singh, Gurmit

publication date

  • January 2020

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