Nigrostriatal dopamine depletion promoted an increase in inhibitory markers (parvalbumin, GAD67, VGAT) and cold allodynia

Neurosci Lett. 2021 Sep 25:762:136135. doi: 10.1016/j.neulet.2021.136135. Epub 2021 Jul 24.

Abstract

Pain constitutes the major non-motor symptom in Parkinson's disease (PD). Its mechanism is still poorly understood although an increase in excitation or a decrease in inhibition have been reported in preclinical studies. The aim of this study was to investigate gamma aminobutyric acid (GABA) inhibition in the 6-hydroxydopamine (6-OHDA) PD rat model. Therefore, the expression of three inhibitory markers parvalbumin, glutamate decarboxylase 67 (GAD67) and vesicular GABA transporter (VGAT) was evaluated, besides cold allodynia, in bilateral 6-OHDA lesioned rat. There was a significant increase in the expression of the three markers labeling within the spinal dorsal horn (SDH) of 6-OHDA lesioned rats. In parallel, there was also an increase of the excitatory marker protein kinase C gamma (PKCγ) . PKCγ cells have a crucial role in pain chronicity and are regulated by GABAergic influences. Central dopamine depletion induced an increase in excitation as reveled by an increase in cFOS expression upon acetone stimulus and the presence of cold allodynia. In addition, dopamine depletion induced increased expression in inhibitory markers, which may reflect a disinhibition or a decreased inhibition in 6-OHDA lesioned rats.

Keywords: Allodynia; Cold; Hyperalgesia; Parkinson’s disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / deficiency
  • Glutamate Decarboxylase / metabolism
  • Hyperalgesia / metabolism*
  • Male
  • Neuralgia / etiology*
  • Neuralgia / metabolism
  • Parkinsonian Disorders / complications*
  • Parkinsonian Disorders / metabolism
  • Parvalbumins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Dorsal Horn / metabolism*
  • Substantia Nigra / metabolism
  • Vesicular Inhibitory Amino Acid Transport Proteins / metabolism

Substances

  • Parvalbumins
  • Slc32a1 protein, rat
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • Dopamine