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

Objectives: 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 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. Conclusions: 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.