GABAergic cell transplants in the anterior cingulate cortex reduce neuropathic pain aversiveness

Brain. 2019 Sep 1;142(9):2655-2669. doi: 10.1093/brain/awz203.

Abstract

Dysfunction of inhibitory circuits in the rostral anterior cingulate cortex underlies the affective (aversive), but not the sensory-discriminative features (hypersensitivity) of the pain experience. To restore inhibitory controls, we transplanted inhibitory interneuron progenitor cells into the rostral anterior cingulate cortex in a chemotherapy-induced neuropathic pain model. The transplants integrated, exerted a GABA-A mediated inhibition of host pyramidal cells and blocked gabapentin preference (i.e. relieved ongoing pain) in a conditioned place preference paradigm. Surprisingly, pain aversiveness persisted when the transplants populated both the rostral and posterior anterior cingulate cortex. We conclude that selective and long lasting inhibition of the rostral anterior cingulate cortex, in the mouse, has a profound pain relieving effect against nerve injury-induced neuropathic pain. However, the interplay between the rostral and posterior anterior cingulate cortices must be considered when examining circuits that influence ongoing pain and pain aversiveness.

Keywords: chemotherapy-induced neuropathic pain; conditioned place preference; gabapentin; medial ganglionic eminence GABAergic cell transplants; pain aversiveness.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • GABAergic Neurons / metabolism*
  • GABAergic Neurons / transplantation*
  • Gyrus Cinguli / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuralgia / metabolism*
  • Neuralgia / pathology
  • Neuralgia / therapy*
  • Receptors, GABA-B / metabolism
  • Sciatic Neuropathy / metabolism
  • Sciatic Neuropathy / pathology
  • Sciatic Neuropathy / therapy*

Substances

  • Receptors, GABA-B