Differential Response to Scrambler Therapy by Neuropathic Pain Phenotypes

Scrambler therapy is a novel noninvasive electroanalgesia technique designed to remodulate the pain system. Despite growing evidence of its efficacy in patients with neuropathic pain, little is known about the clinical factors associated with treatment outcome. We conducted a prospective, open-label, single-arm trial to assess the efficacy and safety of scrambler therapy in patients with chronic neuropathic pain of various etiologies. A post-hoc analysis was performed to investigate whether cluster analysis of the Neuropathic Pain Symptom Inventory profiles could identify a subgroup of patients regarding neuropathic pain phenotype and treatment outcome. Scrambler therapy resulted in a significant decrease in the pain numerical rating scale (NRS) score over 2 weeks of treatment (least squares mean of percentage change from baseline, −15%; 95% CI, −28% to −2.4%; p < 0.001). The mean score of Brief Pain Inventory (BPI) interference subdimension was also significantly improved (p = 0.022), while the BPI pain composite score was not. Hierarchical clustering partitioned the patients into 3 clusters with distinct neuropathic pain phenotypes. Linear mixed-effects model analyses revealed differential response to scrambler therapy across clusters (p = 0.003, pain NRS; p = 0.072, BPI interference subdimension). Treatment response to scrambler therapy appears different depending on the pain-related sensory profile, with more favorable outcomes in patients with preferentially paroxysmal pain rather than persistent pain. Further studies are warranted to confirm that capturing neuropathic pain phenotypes can optimize the use of scrambler therapy.