title: Differences in electrophysiological properties of functionally identified nociceptive sensory neurons in an animal model of cancer-induced bone pain.
abstract: BACKGROUND
  Bone cancer pain is often severe, yet little is known about mechanisms generating this type of chronic pain. While previous studies have identified functional alterations in peripheral sensory neurons that correlate with bone tumours, none has provided direct evidence correlating behavioural nociceptive responses with properties of sensory neurons in an intact bone cancer model.
  
  
  RESULTS
  In a rat model of prostate cancer-induced bone pain, we confirmed tactile hypersensitivity using the von Frey test. Subsequently, we recorded intracellularly from dorsal root ganglion neurons in vivo in anesthetized animals. Neurons remained connected to their peripheral receptive terminals and were classified on the basis of action potential properties, responses to dorsal root stimulation, and to mechanical stimulation of the respective peripheral receptive fields. Neurons included C-, Aδ-, and Aβ-fibre nociceptors, identified by their expression of substance P. We suggest that bone tumour may induce phenotypic changes in peripheral nociceptors and that these could contribute to bone cancer pain.
  
  
  CONCLUSIONS
  This work represents a significant technical and conceptual advance in the study of peripheral nociceptor functions in the development of cancer-induced bone pain. This is the first study to report that changes in sensitivity and excitability of dorsal root ganglion primary afferents directly correspond to mechanical allodynia and hyperalgesia behaviours following prostate cancer cell injection into the femur of rats. Furthermore, our unique combination of techniques has allowed us to follow, in a single neuron, mechanical pain-related behaviours, electrophysiological changes in action potential properties, and dorsal root substance P expression. These data provide a more complete understanding of this unique pain state at the cellular level that may allow for future development of mechanism-based treatments for cancer-induced bone pain.
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Yong Fang
authors.initials: YF
authors.lastname: Zhu
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Ungard
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Seidlitz
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Natalie
authors.initials: N
authors.lastname: Zacal
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jan
authors.initials: J
authors.lastname: Huizinga
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: James L
authors.initials: JL
authors.lastname: Henry
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada singhg@mcmaster.ca.
authors.forename: Gurmit
authors.initials: G
authors.lastname: Singh
mesh_terms: D000200:Action Potentials; D000818:Animals; D001859:Bone Neoplasms / Q000150:complications / Q000473:pathology*; D000072716:Cancer Pain / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D005727:Ganglia, Spinal / Q000473:pathology; D008297:Male; D008959:Models, Neurological; D009412:Nerve Fibers / Q000473:pathology; D009431:Neural Conduction; D009619:Nociceptors / Q000473:pathology*; D010014:Osteolysis / Q000150:complications / Q000473:pathology; D017288:Pain Threshold; D051381:Rats; D013997:Time Factors
keywords: Bone cancer; behaviour; dorsal root ganglion; electrophysiology; pain; primary afferent; prostate cancer