Unilateral lesion of the nigroestriatal pathway with 6-OHDA induced allodynia and hyperalgesia reverted by pramipexol in rats

Eur J Pharmacol. 2020 Feb 15:869:172814. doi: 10.1016/j.ejphar.2019.172814. Epub 2019 Nov 18.

Abstract

Pain is the non-motor symptom with the highest prevalence in patients with Parkinson's Disease (PD) affecting 40-85%. This study aimed to investigate the development of tactile allodynia and mechanical hyperalgesia after the nigrostriatal dopaminergic lesion induced by the unilateral 6-hydroxydopamine (6-OHDA) injection at different doses in the substantia nigra pars compacta (SNpc). Moreover, we studied the possible antiallodynic and antihyperalgesic effect with the acute and the subacute treatment of the pramipexole (PPX) in rats. First, dopaminergic lesion was realized by the unilateral injection of 6-OHDA (6, 10 and 16 μg/μl) into the SNpc. To know the establishment of motor deficits, we measure several turns and forelimb-use asymmetry by rotational behavior and cylinder, respectively. On the other hand, to investigate allodynia and hyperalgesia induced by 6-OHDA, we used the von Frey filaments. Moreover, antiallodynic and antihyperalgesic effect induced by PPX (0.03, 0.3 and 3 mg/kg, s.c.) was examined on acute and subacute conditions. We found that major dopaminergic lesion with 16 μg/μl of 6-OHDA caused the highest allodynia and hyperalgesia effects in both paws, as well as the major motor deficits. In addition, the treatment with PPX at 0.3 mg/kg reverts the allodynia and the hyperalgesia induced by 6-OHDA. In conclusion, the dopaminergic lesion into SNpc induce allodynia and hyperalgesia in both paws; interestingly the treatment with PPX can be suggested as an analgesic drug for patients with PD.

Keywords: 6-Hydroxidopamine; Allodynia; Hyperalgesia; Pain; Parkinson disease; Pramipexole.

MeSH terms

  • Analgesics / therapeutic use*
  • Animals
  • Antiparkinson Agents / therapeutic use*
  • Dopamine Agonists / therapeutic use*
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / etiology
  • Male
  • Oxidopamine
  • Pars Compacta
  • Pramipexole / therapeutic use*
  • Rats, Wistar
  • Touch

Substances

  • Analgesics
  • Antiparkinson Agents
  • Dopamine Agonists
  • Pramipexole
  • Oxidopamine