Identification of spinal circuits involved in touch-evoked dynamic mechanical pain

Nat Neurosci. 2017 Jun;20(6):804-814. doi: 10.1038/nn.4549. Epub 2017 Apr 24.


Mechanical hypersensitivity is a debilitating symptom for millions of chronic pain patients. It exists in distinct forms, including brush-evoked dynamic and filament-evoked punctate hypersensitivities. We reduced dynamic mechanical hypersensitivity induced by nerve injury or inflammation in mice by ablating a group of adult spinal neurons defined by developmental co-expression of VGLUT3 and Lbx1 (VT3Lbx1 neurons): the mice lost brush-evoked nocifensive responses and conditional place aversion. Electrophysiological recordings show that VT3Lbx1 neurons form morphine-resistant polysynaptic pathways relaying inputs from low-threshold Aβ mechanoreceptors to lamina I output neurons. The subset of somatostatin-lineage neurons preserved in VT3Lbx1-neuron-ablated mice is largely sufficient to mediate morphine-sensitive and morphine-resistant forms of von Frey filament-evoked punctate mechanical hypersensitivity. Furthermore, acute silencing of VT3Lbx1 neurons attenuated pre-established dynamic mechanical hypersensitivity induced by nerve injury, suggesting that these neurons may be a cellular target for treating this form of neuropathic pain.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Amino Acid Transport Systems, Acidic / biosynthesis
  • Amino Acid Transport Systems, Acidic / genetics
  • Amino Acid Transport Systems, Acidic / physiology*
  • Animals
  • Avoidance Learning / physiology
  • Clozapine / pharmacology
  • Diphtheria Toxin / pharmacology
  • Female
  • Gene Knock-In Techniques
  • Heparin-binding EGF-like Growth Factor / genetics
  • Hyperalgesia / physiopathology
  • Male
  • Mice
  • Mice, Transgenic
  • Morphine / pharmacology
  • Muscle Proteins / biosynthesis
  • Nerve Fibers, Unmyelinated / physiology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology*
  • Pain Measurement / drug effects
  • Somatostatin / physiology
  • Spinal Cord / drug effects
  • Spinal Cord / physiology*
  • Touch / physiology*


  • Amino Acid Transport Systems, Acidic
  • Diphtheria Toxin
  • Heparin-binding EGF-like Growth Factor
  • Lbx1h protein, mouse
  • Muscle Proteins
  • vesicular glutamate transporter 3, mouse
  • Somatostatin
  • Morphine
  • Clozapine