title: Anatomical changes at the level of the primary synapse in neuropathic pain: evidence from the spinal trigeminal nucleus.
abstract: Accumulated evidence from experimental animal models suggests that neuronal loss within the dorsal horn is involved in the development and/or maintenance of peripheral neuropathic pain. However, to date, no study has specifically investigated whether such neuroanatomical changes also occur at this level in humans. Using brain imaging techniques, we sought to determine whether anatomical changes were present in the spinal trigeminal nucleus in subjects with chronic orofacial neuropathic pain. In 22 subjects with painful trigeminal neuropathy and 44 pain-free controls, voxel-based morphometry of T1-weighted anatomical images and diffusion tensor images were used to assess regional gray matter volume and microstructural changes within the brainstem. In addition, deterministic tractography was used to assess the integrity of ascending pain pathways. Orofacial neuropathic pain was associated with significant regional gray matter volume decreases, fractional anisotropy increases, and mean diffusivity decreases within the spinal trigeminal nucleus, specifically the subnucleus oralis. In addition, tractography revealed no significant differences in diffusivity properties in the root entry zone of the trigeminal nerve, the spinal trigeminal tract, or the ventral trigeminothalamic tracts in painful trigeminal neuropathy subjects compared with controls. These data reveal that chronic neuropathic pain in humans is associated with discrete alterations in the anatomy of the primary synapse. These neuroanatomical changes may be critical for the generation and/or maintenance of pathological pain.
authors: Department of Anatomy and Histology, University of Sydney, Sydney, New South Wales, Australia 2006.
authors: Sophie L
authors: SL
authors: Wilcox
authors: Department of Anatomy and Histology, University of Sydney, Sydney, New South Wales, Australia 2006.
authors: Sylvia M
authors: SM
authors: Gustin
authors: University of California, Los Angeles, School of Nursing and Brain Research Institute, Los Angeles, California 90095, and.
authors: Paul M
authors: PM
authors: Macey
authors: Jaw Function and Orofacial Pain Research Unit, Faculty of Dentistry, Westmead Hospital, University of Sydney, Australia 2145.
authors: Chris C
authors: CC
authors: Peck
authors: Jaw Function and Orofacial Pain Research Unit, Faculty of Dentistry, Westmead Hospital, University of Sydney, Australia 2145.
authors: Greg M
authors: GM
authors: Murray
authors: Department of Anatomy and Histology, University of Sydney, Sydney, New South Wales, Australia 2006, lukeh@anatomy.usyd.edu.au.
authors: Luke A
authors: http://orcid.org/0000-0002-1026-0151
authors: LA
authors: Henderson
mesh_terms: D000328:Adult; D000368:Aged; D001933:Brain Stem / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000473:pathology*; D009473:Neuronal Plasticity; D010147:Pain Measurement; D013569:Synapses / Q000473:pathology*; D020433:Trigeminal Nerve Diseases / Q000473:pathology*; D014279:Trigeminal Nucleus, Spinal / Q000473:pathology*
keywords: brainstem; dorsal horn; magnetic resonance imaging; tractography; trigeminal neuropathy