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



Nasirinezhad F¹ ; Zarepour L¹ ; Hadjighassem M² ; Gharaylou Z² ; Majedi H² ; Ramezani F¹ Show Affiliations
Source: Basic and Clinical Neuroscience Published:2021

Abstract

Objectives: The current study evaluated the analgesic effects of bumetanide as an adjunctive treatment in the management of neuropathic pain following spinal cord injury. The peripheral expression of Na-K-Cl-cotransporter-1 1 and K-Cl-cotransporter-2 (KCC2)2 genes in polymorphonuclear lymphocytes (PMLs) assessed as a possible biomarker indicating central mechanisms underlying the observed response. Methods: Through an open-label, single arm, pilot trial of bumetanide (2mg/day), as add-on treatment conducted in 14 SCI patients for 19 weeks. This study consisted of 3 phases: pretreatment (1month), 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 McGill Pain Questionnaire. Secondary endpoints included the Short-Form 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 accompanied by the greater mean change from the baseline (improvement) for the overall quality of life. Conclusions: These data highlighted the analgesic effect of bumetanide on neuropathic pain and indicated the probable role of upregulation of KCC2 protein and involvement of GABAergic disinhibition in producing neuropathic pain. © 2021 Iran University of Medical Sciences. All rights reserved.