Sumatriptan improves the locomotor activity and neuropathic pain by modulating neuroinflammation in rat model of spinal cord injury

Neurol Res. 2021 Jan;43(1):29-39. doi: 10.1080/01616412.2020.1819090. Epub 2020 Sep 16.

Abstract

Objectives: To investigate the therapeutic effects of sumatriptan in a rat model of spinal cord injury (SCI) and possible anti-inflammatory and analgesic mechanisms underlying this effect.

Methods: Using an aneurysm mini-clip model of contusive SCI, T9-10 laminectomies were performed for 60 male rats. Animals were divided into six experimental groups (n = 10 per group) as follows: a minocycline administered positive control group, a saline-vehicle negative control group, a sham-operated group, and three experimental groups which received separate doses of sumatriptan (0.1, 0.3 and 1 mg/kg). Behavioural assessments were used to evaluate locomotor activity and neuropathic pain for 28 days. At the end of the study, spinal cord tissues were collected from sacrificed animals for histopathological analysis. Levels of calcitonin gene-related peptide (CGRP) and two pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-1β) were assessed by the enzyme-linked immunosorbent assay (ELISA).

Results: Sumatriptan significantly (P < 0.001) improved the locomotor activity in SCI group. Sumatriptan was also more effective than the positive control, i.e. minocycline (0.3 mg/kg). Additionally, sumatriptan and minocycline similarly attenuated the mechanical and thermal allodynia in SCI (P < 0.001). TNF-α, IL-1β and CGRP levels in sumatriptan- and minocycline-treated groups significantly (P < 0.001) decreased compared to controls. Histopathological analysis also revealed a markedly improvement in hemorrhage followed by inflammatory cell invasion, neuronal vacuolation, and cyst formation in both sumatriptan- and minocycline-treated groups compared to control animals.

Conclusions: Sumatriptan improves functional recovery from SCI through its anti-inflammatory effects and reducing pro-inflammatory and pain mediators.

Keywords: Sumatriptan; neuroinflammation; neuropathic pain; spinal cord injury.

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Disease Models, Animal
  • Inflammation / etiology
  • Locomotion / drug effects*
  • Male
  • Neuralgia* / etiology
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Spinal Cord / drug effects
  • Spinal Cord / pathology
  • Spinal Cord Injuries* / complications
  • Spinal Cord Injuries* / pathology
  • Sumatriptan / pharmacology*

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Sumatriptan