title: Lack of evidence for ectopic sprouting of genetically labeled Aβ touch afferents in inflammatory and neuropathic trigeminal pain.
abstract: BACKGROUND
  Mechanical and in particular tactile allodynia is a hallmark of chronic pain in which innocuous touch becomes painful. Previous cholera toxin B (CTB)-based neural tracing experiments and electrophysiology studies had suggested that aberrant axon sprouting from touch sensory afferents into pain-processing laminae after injury is a possible anatomical substrate underlying mechanical allodynia. This hypothesis was later challenged by experiments using intra-axonal labeling of A-fiber neurons, as well as single-neuron labeling of electrophysiologically identified sensory neurons. However, no studies have used genetically labeled neurons to examine this issue, and most studies were performed on spinal but not trigeminal sensory neurons which are the relevant neurons for orofacial pain, where allodynia oftentimes plays a dominant clinical role.
  
  
  RESULTS
  We recently discovered that parvalbumin::Cre (Pv::Cre) labels two types of Aβ touch neurons in trigeminal ganglion. Using a Pv::CreER driver and a Cre-dependent reporter mouse, we specifically labeled these Aβ trigeminal touch afferents by timed taxomifen injection prior to inflammation or infraorbital nerve injury (ION transection). We then examined the peripheral and central projections of labeled axons into the brainstem caudalis nucleus after injuries vs controls. We found no evidence for ectopic sprouting of Pv::CreER labeled trigeminal Aβ axons into the superficial trigeminal noci-receptive laminae. Furthermore, there was also no evidence for peripheral sprouting.
  
  
  CONCLUSIONS
  CreER-based labeling prior to injury precluded the issue of phenotypic changes of neurons after injury. Our results suggest that touch allodynia in chronic orofacial pain is unlikely caused by ectopic sprouting of Aβ trigeminal afferents.
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC, 27710, USA. yi.zhang3@dm.duke.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Center for Translational Neuroscience, Duke University Medical Center, Durham, NC, 27710, USA. yong.chen@dm.duke.edu.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, Center for Translational Neuroscience, Duke University Medical Center, Durham, NC, 27710, USA. wolfgang@neuro.duke.edu.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Liedtke
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC, 27710, USA. fan.wang@duke.edu.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology*; D000818:Animals; D001369:Axons / Q000378:metabolism; D006930:Hyperalgesia / Q000235:genetics / Q000503:physiopathology*; D007249:Inflammation / Q000235:genetics; D051379:Mice; D009437:Neuralgia / Q000235:genetics / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation / Q000379:methods; D013116:Spinal Cord / Q000503:physiopathology; D014110:Touch / Q000502:physiology*