Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury

Cell Rep. 2015 Nov 10;13(6):1246-1257. doi: 10.1016/j.celrep.2015.09.080. Epub 2015 Oct 29.


Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, the molecular and cellular mechanisms underlying this disinhibition are unclear. Here, we combined pharmacogenetic activation and selective ablation approaches in mice to define the contribution of spinal cord parvalbumin (PV)-expressing inhibitory interneurons in naive and neuropathic pain conditions. Ablating PV neurons in naive mice produce neuropathic pain-like mechanical allodynia via disinhibition of PKCγ excitatory interneurons. Conversely, activating PV neurons in nerve-injured mice alleviates mechanical hypersensitivity. These findings indicate that PV interneurons are modality-specific filters that gate mechanical but not thermal inputs to the dorsal horn and that increasing PV interneuron activity can ameliorate the mechanical hypersensitivity that develops following nerve injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Hyperalgesia / pathology
  • Hyperalgesia / physiopathology*
  • Interneurons / metabolism
  • Interneurons / pathology
  • Interneurons / physiology*
  • Mice
  • Neuralgia / pathology
  • Neuralgia / physiopathology*
  • Parvalbumins / genetics
  • Parvalbumins / metabolism
  • Protein Kinase C / metabolism
  • Spinal Cord Dorsal Horn / pathology
  • Spinal Cord Dorsal Horn / physiology*
  • Spinal Cord Dorsal Horn / physiopathology
  • Synapses / metabolism
  • Synapses / physiology
  • Touch


  • Parvalbumins
  • protein kinase C gamma
  • Protein Kinase C