High-frequency spinal cord stimulation improves pain in refractory painful diabetic neuropathy
A randomized clinical trial (RCT) in 216 patients with painful diabetic neuropathy (PDN) refractory to ≥1 year of treatment with gabapentinoids and ≥1 other analgesic class shows that high-frequency (10 kHz) spinal cord stimulation (SCS) plus conventional medical management (CMM) is superior to CMM alone in terms of pain relief and health-related quality of life (HRQoL).
“Approximately 20 percent of patients with diabetes develop PDN – a progressive, potentially debilitating chronic neuropathic pain condition,” wrote the researchers. [Clin J Pain 2002;18:350-354] “[Yet] high-quality RCTs demonstrate limited efficacy of neuropathic pain medications, such as gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, opioids, and topical solutions, with high incidence of adverse effects.” [Diabetes Care 2017;40:136-154; Drug Ther Bull 2018;56:3-4; Am J Health Syst Pharm 2017;74:162-169]
Observational data suggest that high-frequency SCS provides substantial pain relief for patients with PDN. [Postgrad Med 2020;132:352-357; Pain Manag 2020;10:291-300] “To our knowledge, the current SENZA-PDN RCT is the largest to date to test the hypothesis that 10 kHz SCS combined with CMM provides meaningful pain relief compared with CMM alone for patients with refractory PDN,” wrote the trial investigators. [Trials 2020;21:1-12]
Medically suitable PDN patients with lower limb pain intensity of 5 cm or more on a 10-cm visual analogue scale (VAS) underwent temporary trial SCS for 5–7 days with percutaneous leads placed epidurally along T8 to T11. Patients reporting ≥50 percent pain relief on the VAS were eligible for permanent SCS device implant, which included two percutaneous leads placed epidurally and connected to an implantable pulse generator typically placed in the lower back. [JAMA Neurol 2021; doi:10.1001/jamaneurol.2021.0538]
In the CMM alone group, five of 94 patients (5 percent) met the composite primary endpoint of ≥50 percent pain relief based on the VAS without observed deterioration on neurological examination, compared with 75 of 95 patients (79 percent) in the 10 kHz SCS plus CMM group (difference, 73.6 percent; 95 percent confidence interval [CI], 64.2 to 83.0; p<0.001). The mean pain VAS score at 6 months was 1.3 cm (95 percent CI, 1.0 to 1.6) in patients treated with 10 kHz SCS plus CMM, representing a mean reduction from baseline of 82.3 percent (95 percent CI, 78.5 to 86.1).
There was no change in HRQoL EuroQol 5-Dimension Questionnaire (EQ-5D-5L) VAS scores from baseline for patients in the CMM group, while those treated with 10 kHz SCS plus CMM showed a mean improvement of 16 points (p<0.001). At 6 months, there was a minor decrease in mean EQ-5D-5L index score in the CMM alone group, while the mean score improved by 0.129 points in the 10 kHz SCS plus CMM group (p<0.001). “The minimally important difference is estimated between 0.03 to 0.05 in the type 2 diabetes population,” noted the investigators. [Value Health 2018;21:1090-1097]
“Wound complications are a primary concern when performing surgical procedures for patients with diabetes. Wound dehiscence, impaired healing, or infection was seen in five of 90 patients with permanent SCS implant, translating to a 5.6 percent wound complication rate. This is consistent with the risk for SCS wound complications in general and suggests that implantation of an SCS device can be safely accomplished in patients with diabetes,” reported the investigators. [Pain Med 2016;17:325-336]
Of 90 patients implanted with SCS device, two required explant. There were no stimulation-related neurological deficits in the 10 kHz SCS plus CMM group.