Analgesic Effect of Bumetanide on Neuropathic Pain in Patients With Spinal Cord Injury.

Content Provider	Europe PMC
Author	Nasirinezhad, Farinaz Zarepour, Leila Hadjighassem, Mahmoudreza Gharaylou, Zeinab Majedi, Hossin Ramezani, Fatemeh
Copyright Year	2021
Abstract	Introduction:The current study evaluated the analgesic effects of bumetanide as an adjunctive in the management of neuropathic pain following Spinal Cord Injury (SCI). The peripheral expression of Na-K-Cl Cotransporter-1 (NKCC1) and K-Cl Cotransporter-2 (KCC2) genes in polymorphonuclear lymphocytes (PMLs) was assessed as a possible biomarker indicating central mechanisms underlying the observed response.Methods:Through an open-label, single-arm, pilot trial of bumetanide (2 mg/d), an add-on treatment was conducted on 14 SCI patients for 19 weeks. This study consisted of 3 phases: pre-treatment (1 month), titration (3 weeks), and active treatment (4 months). Ultimately, 9 patients completed the study. The primary outcome variables were the endpoint pain score using the Numeric Rating Scale (NRS), and also the short-form of the McGill pain questionnaire. Secondary endpoints included the short-form of the health survey that assesses the quality of life. Blood samples were collected and used for determining the expression of NKCC1 and KCC2 genes in transcription and translation levels.Results:Bumetanide treatment significantly decreased average pain intensity according to the NRS and the short-form of the McGill pain questionnaire scores. Baseline expression of KCC2 protein was low between groups and increased significantly following treatment (P<0.05). In the current study, pain improvement was accompanied by the greater mean change from the baseline (improvement) for the overall quality of life.Conclusion:These data highlighted the analgesic effect of bumetanide on neuropathic pain and indicated the potential role of the upregulation of KCC2 protein and involvement of GABAergic disinhibition in producing neuropathic pain.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC8666921&blobtype=pdf
ISSN	2008126X
Journal	Basic and Clinical Neuroscience [Basic Clin Neurosci]
Volume Number	12
DOI	10.32598/bcn.12.3.2049.1
PubMed Central reference number	PMC8666921
Issue Number	3
PubMed reference number	34917299
e-ISSN	22287442
Language	English
Publisher	Iranian Neuroscience Society
Publisher Date	2021-05-01
Access Restriction	Open
Rights License	This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ Copyright© 2021 Iranian Neuroscience Society
Subject Keyword	Bumetanide Na-K-Cl Cotransporter-1 (NKCC1) K-Cl Cotransporter-2 (KCC2) Neuropathic pain Spinal cord injury GammaAminobutyric Acid (GABA)
Content Type	Text
Resource Type	Article
Subject	Neurology (clinical) Cellular and Molecular Neuroscience