Nature 462, 651-655 (3 December 2009) | doi:10.1038/nature08505; Received 14 May 2009; Accepted 17 September 2009; Published online 15 November 2009; Corrected 3 December 2009

Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors

Rebecca P. Seal1,5, Xidao Wang2,5, Yun Guan3, Srinivasa N. Raja3, C. Jeffery Woodbury4, Allan I. Basbaum2 & Robert H. Edwards1

  1. Departments of Physiology and Neurology, University of California, San Francisco School of Medicine, California 94143, USA
  2. Departments of Anatomy and Physiology, University of California, San Francisco School of Medicine, California 94158, USA
  3. Department of Anesthesiology and Critical Care Medicine, the Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA
  4. Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
  5. These authors contributed equally to the work.

Correspondence to: Robert H. Edwards1 Correspondence and requests for materials should be addressed to R.H.E. (Email: robert.edwards@ucsf.edu).

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 glutamate1, 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 injury2. Because the different VGLUT isoforms generally have a non-redundant pattern of expression3, 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)4, 5. The analysis of Vglut3 -/- mice now indicates a critical role for C-LTMRs in the mechanical hypersensitivity caused by injury.


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