Acute administration of levetiracetam in tonic pain model modulates gene expression of 5HT1A and 5HT7 receptors in the thalamus of rats (Rattus norvergicus)

Mol Biol Rep. 2020 May;47(5):3389-3396. doi: 10.1007/s11033-020-05419-1. Epub 2020 Apr 13.

Abstract

The nociceptive effect of Levetiracetam (LEV) on the expression of 5-HT1A and 5-HT7 receptors found in the thalamus was evaluated. Thirty-six male rats (Wistar) were randomized into six groups: in the Control group without treatment; LEV50 group LEV was administered in a single dose of 50 mg/kg i.g.; in the LEV300 group LEV dose of 300 mg/kg i.g.; in the FORMALIN group the formalin test was performed; in the LEV50/FORMALIN group LEV dose of 50 mg/kg i.g and the formalin test was performed; in the LEV300/FORMALIN group LEV dose of 300 mg/kg i.g and the formalin test was performed, subsequently the thalamus was dissected in all groups. In the formalin tests LEV exhibited an antinociceptive effect in the LEV300/FORMALIN group (p < 0.05) and a pronociceptive effect in the LEV50/FORMALIN group (p < 0.001). The results obtained by Real-time PCR confirmed the expression of the 5-HT1A and 5-HT7 receptors in the thalamus, 5-HT1A receptors increased significantly in the FORMALIN group and the LEV300/FORMALIN group (p < 0.05). 5-HT7 receptors are only over expressed at a dose of 300 mg/Kg of LEV with formalin (p < 0.05). This suggests that LEV modulates the sensation of pain by controlling the expression of 5-HT1A and 5-HT7 in a tonic pain model, and that changes in the expression of 5-HT1A and 5-HT7 receptors are associated with the sensation of pain, furthermore its possibility to be used in clinical treatments for pain.

Keywords: Levetiracetam; Receptor 5-HT1A; Receptor 5-HT7; Serotonin; Thalamus; Tonic pain.

MeSH terms

  • Animals
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Levetiracetam / metabolism
  • Levetiracetam / pharmacology*
  • Male
  • Pain / drug therapy
  • Pain / genetics
  • Pain Measurement / methods
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A / genetics*
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptors, Serotonin / genetics*
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin / physiology
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Thalamus / metabolism

Substances

  • Receptors, Serotonin
  • Serotonin Plasma Membrane Transport Proteins
  • serotonin 7 receptor
  • Receptor, Serotonin, 5-HT1A
  • Levetiracetam