A novel gabapentin analogue assuages neuropathic pain response in chronic sciatic nerve constriction model in rats

Behav Brain Res. 2021 May 7:405:113190. doi: 10.1016/j.bbr.2021.113190. Epub 2021 Feb 16.

Abstract

Gabapentin (GBP) is an established drug that has been used in the management of symptoms of neuropathy but it is associated with unwanted side effects such as sedation and motor incoordination. The goal of the study was to find out a drug with greater efficacy and safety for the treatment of neuropathic pain. Our previously synthesized GABA analogue (Gabapentsal, GPS) was tested (25-100 mg/kg, i.p) in chronic constriction injury (CCI) induced nociceptive model of static allodynia, dynamic allodynia, thermal hyperalgesia, mechanical hyperalgesia and cold allodynia in rats (Sprague Dawley). Open field and rotarod tests were performed to assess the impact of GPS on the motor performance of the animals. GBP (100 mg/kg, i.p) was used as a standard for comparison. GPS dose dependently reduced static (P <0.001) and dynamic allodynia (P <0.001), thermal hyperalgesia (P <0.001), mechanical hyperalgesia (P < 0.001) and cold allodynia (P < 0.001). In comparison to GBP, GPS failed to alter any significantly the motor performance of rats in both the open field and rotarod assays. These results suggest that GPS is effective in alleviating nociception in CCI neuropathic pain model but free from the side effect of motor discoordination seen in the treatment with GBP. In conclusion, GPS may prove to be a prospectively more effective and safer option in the management of neuropathic syndromes.

Keywords: Allodynia; Chronic constriction injury; Gabapentin; Gabapentsal; Neuropathic pain; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / adverse effects
  • Analgesics / pharmacology*
  • Animals
  • Behavior, Animal / drug effects*
  • Chronic Disease
  • Constriction
  • Disease Models, Animal
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / adverse effects
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Gabapentin / analysis*
  • Hyperalgesia / drug therapy*
  • Male
  • Neuralgia / drug therapy*
  • Neuralgia / etiology
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Neuropathy / complications

Substances

  • Analgesics
  • Excitatory Amino Acid Antagonists
  • Gabapentin