Reduced GABAergic transmission in the ventrobasal thalamus contributes to thermal hyperalgesia in chronic inflammatory pain

Sci Rep. 2017 Feb 2;7:41439. doi: 10.1038/srep41439.

Abstract

The ventrobasal (VB) thalamus is innervated by GABAergic afferents from the thalamic reticular nucleus (TRN) and participates in nociception. But how the TRN-VB pathway regulates pain is not fully understood. In the present study, we reported decreased extracellular GABA levels in the VB of rats with CFA-induced chronic inflammatory pain, measured by microdialysis with HPLC analysis. In vitro whole-cell patch-clamp recording showed decreased amplitudes of tonic currents, increased frequencies of mIPSCs, and increased paired-pulse ratios in thalamic slices from chronic inflammatory rats (7 days). Microinjection of the GABAAR agonist muscimol and optogenetic activation of the TRN-VB pathway relieved thermal hyperalgesia in chronic inflammatory pain. By contrast, microinjecting the extrasynaptic GABAAR agonist THIP or selective knockout of synaptic GABAAR γ2 subunits aggravated thermal hyperalgesia in the chronic stage of inflammatory pain. Our findings indicate that reduced GABAergic transmission in the VB contributes to thermal hyperalgesia in chronic inflammatory pain, which could be a synaptic target for pharmacotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Pain / complications
  • Chronic Pain / physiopathology*
  • Extracellular Space / metabolism
  • Freund's Adjuvant
  • GABAergic Neurons / physiology*
  • Gene Knockout Techniques
  • Hyperalgesia / complications
  • Hyperalgesia / physiopathology*
  • Inflammation / complications
  • Inflammation / physiopathology*
  • Isoxazoles / pharmacology
  • Male
  • Muscimol / pharmacology
  • Optogenetics
  • Patch-Clamp Techniques
  • Protein Subunits / metabolism
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / metabolism
  • Synaptic Transmission*
  • Thalamus / pathology
  • Thalamus / physiopathology*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Isoxazoles
  • Protein Subunits
  • Receptors, GABA-A
  • Muscimol
  • gamma-Aminobutyric Acid
  • Freund's Adjuvant
  • gaboxadol