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Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors.

Mechanical pain contributes to the morbidity associated with inflammation and trauma, but primary sensory neurons that convey the sensation of acute and persistent mechanical pain have not been identified. Dorsal root ganglion (DRG) neurons transmit sensory information to the spinal cord using the excitatory transmitter glutamate, a process that depends on glutamate transport into synaptic vesicles for regulated exocytotic release. Here we report that a small subset of cells in the DRG expresses the low abundance vesicular glutamate transporter VGLUT3 (also known as SLC17A8). In the dorsal horn of the spinal cord, these afferents project to lamina I and the innermost layer of lamina II, which has previously been implicated in persistent pain caused by injury. Because the different VGLUT isoforms generally have a non-redundant pattern of expression, we used Vglut3 knockout mice to assess the role of VGLUT3(+) primary afferents in the behavioural response to somatosensory input. The loss of VGLUT3 specifically impairs mechanical pain sensation, and in particular the mechanical hypersensitivity to normally innocuous stimuli that accompanies inflammation, nerve injury and trauma. Direct recording from VGLUT3(+) neurons in the DRG further identifies them as a poorly understood population of unmyelinated, low threshold mechanoreceptors (C-LTMRs). The analysis of Vglut3(-/-) mice now indicates a critical role for C-LTMRs in the mechanical hypersensitivity caused by injury.

Pubmed ID: 19915548

Authors

  • Seal RP
  • Wang X
  • Guan Y
  • Raja SN
  • Woodbury CJ
  • Basbaum AI
  • Edwards RH

Journal

Nature

Publication Data

December 3, 2009

Associated Grants

  • Agency: NIMH NIH HHS, Id: F32 MH068085
  • Agency: NIMH NIH HHS, Id: F32 MH068085-02
  • Agency: NIMH NIH HHS, Id: R01 MH050712
  • Agency: NIMH NIH HHS, Id: R01 MH050712-17
  • Agency: NINDS NIH HHS, Id: R01 NS044094
  • Agency: NINDS NIH HHS, Id: R01 NS044094-06

Mesh Terms

  • Amino Acid Transport Systems, Acidic
  • Animals
  • Behavior, Animal
  • Female
  • Ganglia, Spinal
  • Gene Expression Regulation
  • Hypersensitivity
  • Mechanoreceptors
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pain
  • Wounds and Injuries