Molecular Inflammatory Characteristics of Patients With Chronic Pain Under Burst Spinal Cord Stimulation: An Exploratory Study

Neuromodulation. 2026 Jul 6:S1094-7159(26)00633-1. doi: 10.1016/j.neurom.2026.06.472. Online ahead of print.

ABSTRACT

OBJECTIVES: Spinal cord stimulation (SCS) has been reported to reduce chronic back and leg pain and improve functional capacity. However, its mechanism of action is not completely understood. One proposed mechanism involves the modulation of central and peripheral inflammatory circuits.

MATERIAL AND METHODS: This exploratory study enrolled 28 participants (11 healthy controls [HC] and 17 patients with chronic back and/or leg pain of various origin). Pain intensity (Numeric Rating Scale), sleep quality (Pittsburgh Sleep Quality Index), mood (Beck Depression Inventory), disability (Oswestry Disability Index), and levels of pro- and anti-inflammatory cytokines (adiponectin, ghrelin, interleukin [IL]-10, high-mobility group box 1-protein, tumor necrosis factor alpha, IL-6, IL-1β, leptin) were collected at baseline and after three months of burst SCS and compared with HC.

RESULTS: A total of 11 men and six women (mean age 68.4 ± 11.2 years) underwent permanent SCS implantation. Pain intensity significantly decreased at follow-up (p < 0.001), accompanied by improvements in sleep quality (p = 0.002), mood (p = 0.001), and disability (p < 0.001). At baseline, proinflammatory tumor necrosis factor alpha levels were significantly elevated (p = 0.006), whereas anti-inflammatory IL-10 levels were significantly reduced compared with HC (p = 0.004). At follow-up, IL-10 levels increased, attenuating the difference between patients and HC such that no statistical significance was observed. Levels of pro- and anti-inflammatory cytokines showed no significant correlations with clinical outcome measures.

CONCLUSIONS: Consistent with previously published data, we found a proinflammatory profile in patients with chronic pain at baseline. After three months of burst SCS anti-inflammatory IL-10 was increased along with improved pain and functional capacity. However, a causal relationship between burst SCS and neuroinflammatory mediators in chronic back and/or leg pain could not be established.

PMID:42489599 | DOI:10.1016/j.neurom.2026.06.472