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Sumatriptan Improves the Locomotor Activity and Neuropathic Pain by Modulating Neuroinflammation in Rat Model of Spinal Cord Injury Publisher Pubmed



Afshari K1, 2 ; Dehdashtian A1, 2 ; Haddad NS2 ; Jazaeri SZ1 ; Ursu DC3 ; Khalilzadeh M2 ; Hajmirzaian A1, 2 ; Shakiba S1, 2 ; Burns TC4 ; Tavangar SM5, 6 ; Ghasemi M7 ; Dehpour AR2, 8
Authors
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Authors Affiliations
  1. 1. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Surgery, Section of Plastic and Reconstructive Surgery, University of Michigan, United States
  4. 4. Department of Neurological Surgery, Mayo Clinic Rochester, United States
  5. 5. Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Neurology, University of Massachusetts School of Medicine, Worcester, MA, United States
  8. 8. Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Neurological Research Published:2021


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. © 2020 Informa UK Limited, trading as Taylor & Francis Group.
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