The Elevated Serum Level of IFN-γ in Patients with Failed Back Surgery Syndrome Remains Unchanged after Spinal Cord Stimulation.

OBJECTIVES: We investigated the influence of spinal cord stimulation (SCS) on IFN-γ, IL-1ß, IL-6, TNF-α, IL-10, and TGF-ß serum levels in failed back surgery syndrome (FBSS) patients. The study will try to give new insights into the mechanism of SCS action and the role of IFN-γ and other cytokines in neuropathic pain (NP) development. MATERIALS AND METHODS: Clinical and biochemical assessment was conducted in four groups of patients: group 0 consisted of 24 FBSS patients qualified to SCS therapy, group 1 included 17 patients who were one month after implantation, group 2 featured 12 patients who were 3 months after the implantation, and group C (the control group) with no NP. Clinical status was assessed with the use of Numeric Rating Scale (NRS), the Pain Rating Index of McGill Pain Questionnaire (SF-MPQ), the Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). The plasma concentrations of IFN-γ were ascertained by an immunoenzymatic method. RESULTS: We found a significant difference between the patients before SCS and controls' serum level of IFN-γ. Similarly, a significantly higher level of TNF-α and significantly lower level of IL-10 in FBSS patients than controls were observed. The significant differences were not observed between SCS patients 3 months after the procedure and controls' serum level of IFN-γ and other cytokines. We noticed a positive correlation between IFN-γ concentration with NRS back value before SCS and positive correlation between IFN-γ concentration after SCS with NRS leg value before SCS. Higher IFN-γ concentrations accompanied higher NRS values. Levels of TGF-ß and IL-10 may correlate with physical ability and depressive behavior. CONCLUSIONS: SCS did not influence serum cytokine levels significantly. Serum concentration of IFN-γ may be recognized as an occasional pain factor because of its significantly higher level in FBSS patients versus controls and higher IFN-γ value accompanying higher pain intensity.

Serum Level of Metalloproteinase-2 but not Metalloproteinase-9 Rises in Patients With Failed Back Surgery Syndrome After Spinal Cord Stimulation.

OBJECTIVES: The impact of spinal cord stimulation (SCS) on serum levels of metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) was assessed in a group of patients with failed back surgery syndrome (FBSS). The study was to give new insights into the SCS mechanism of action and the role of MMP-2 and MMP-9 in the development of NP. MATERIAL AND METHODS: Clinical assessments were performed and biochemical markers were determined in two groups of patients: the control group (24 individuals) and the FBSS group (24 patients). Seventeen patients with the FBSS had SCS implanted and were examined before surgical procedure, one month after (17 patients), and three months after operation (12 patients). Clinical status was assessed with the use numeric rating scale, pain rating index of McGill pain questionnaire, Oswestry disability index and Beck depression inventory. MMP-2 and MMP-9 serum levels were determined using gelatin zymography. Immunoenzymatic method was employed to determine plasma concentrations of tissue inhibitors of metalloproteinases (TIMPs). RESULTS: Levels of MMP-2 and TIMP-2 were higher in the FBSS group compared to the control group. The difference was statistically significant (p < 0.001 and p = 0.004, respectively). The concentration of MMP-2 was significantly increased (p = 0.0135) one-month post-SCS and remained elevated but stable up to three months after implantation. TIMP-2, MMP-2/TIMP-2, MMP-9, TIMP-1, and MMP-9/TIMP-1 serum levels did not change significantly. CONCLUSIONS: MMPs may play a role in the development of FBSS. SCS increases the already elevated MMP-2 serum levels which are associated with neuroinflammatory processes in FBSS patients.

Burst Spinal Cord Stimulation Increases Peripheral Antineuroinflammatory Interleukin 10 Levels in Failed Back Surgery Syndrome Patients With Predominant Back Pain.

OBJECTIVES: Burst spinal cord stimulation (SCS) has been reported to reduce back pain and improve functional capacity in Failed Back Surgery Syndrome (FBSS). However, its mechanism of action is not completely understood. Systemic circulating cytokines have been associated with the development of chronic back pain. METHODS: This prospective, feasibility study enrolled 12 refractory FBSS patients with predominant back pain (70% of overall pain) suitable for Burst SCS. Back and leg pain intensity (back pain [VASB ]/leg pain [VASL ]), functional capacity (sleep quality [PSQI]), depressive symptoms (BDI), body weight, stimulation parameters, and plasma levels of pro-inflammatory (Il-1b; TNF; HMGB1)/anti-inflammatory (Il-10) cytokines were collected at baseline and after three months of Burst SCS and compared to healthy controls. RESULTS: Pain intensity (pre VASB : 8.25 ± 0.75 vs. post 1.42 ± 1.24) and functional capacity (PSQI: pre 7.92 ± 3.92 vs. post 3.42 ± 1.24; BDI: pre 20.83 ± 3.56 vs. post 10.92 ± 0.75) significantly improved compared to baseline. Pro-inflammatory HMGB1 remained unchanged (preburst: 3.35 ± 3.25 vs. postburst: 3.78 ± 3.83 ng/mL; p = 0.27; W = -30) versus the HC group (2.53 ± 2.6 ng/mL; p = 0.47; U = 59), while anti-inflammatory IL-10 levels were significantly elevated after burst SCS as compared to baseline (preburst 12.54 ± 22.95 vs. postburst 43.16 ± 74.71 pg/mL; p = 0.03; W = -48) and HC group (HC: 7.03 ± 11.6 vs. postburst 43.16 ± 74.71 pg/mL; p = 0.03; W = -48; p = 0.04). Baseline preburst IL-10 values and preburst VASB significantly correlated (Spearman correlation r = -0.66; p = 0.05; 95 CI -0.86 to -0.24), while correlation was not significant between postburst IL-10 values and postburst VASB (Spearman correlation r = -0.49; p = 0.18; 95 CI -0.83 to -0.15). Postburst IL-10 values correlated significantly with postburst PSQI scores (Spearman correlation r = -0.66; p = 0.05; 95 CI -0.86 to -0.24), while no correlation was found between preburst and postburst changes related to the BDI. CONCLUSIONS: Burst SCS increased systemic circulating anti-inflammatory IL-10, improved FBSS back pain and back pain associated co-morbidities like disrupted sleep architecture and depressive symptoms in FBSS patients. Thus, suggesting a possible relationship between burst SCS and burst-evoked modulation of peripheral anti-inflammatory cytokine IL-10 in chronic back pain.

Serum 25-hydroxy-calciferol level and failed back surgery syndrome.

PURPOSE: To assess the association of serum 25-hydroxy-calciferol levels with pain and low back function in patients with failed back surgery syndrome. METHODS: Records of 6 men and 3 women aged 25 to 54 (mean, 39.2) years who had failed back surgery syndrome after pedicular screw and rod instrumentation for lower lumbar degenerative diseases were reviewed. They had moderate-to-severe pain (visual analogue scale [VAS] score of >6) and low back function disability (Japanese Orthopaedic Association [JOA] back score of <10). In all patients, the serum 25-hydroxy-calciferol level was <30 ng/ ml, indicating vitamin D deficiency. Vitamin D2 (20 000 IU per day) was given for 10 days, and vitamin D3 (600 IU per day) was given for maintenance. Patients were followed up at months 3 and 6. Three men and 4 women aged 27 to 55 (mean, 41.3) years who were age- and disease-matched but achieved good outcomes (VAS score of 0-1 and mean JOA low back score of 14.7) were used as indirect referents. All 7 matched patients except one had a normal serum 25-hydroxy-calciferol level (mean, 40.6 ng/ml). RESULTS: In the 9 patients with failed back surgery syndrome, the mean duration of chronic pain was 2.6 years; the mean VAS score for pain was 7.7; the mean JOA low back score was 7.6; the mean number of reoperations was 2.2; and the mean serum 25-hydroxy-calciferol level was 17.0 ng/ml. Two male patients had grade-IV motor weakness and decreased sensory function based on the pin prick test. One patient had a history of prolonged (>3 months) antibiotic use after primary surgery, but had no evidence of infection. Six months after vitamin D2 and vitamin D3 supplementation, the mean serum 25-hydroxy-calciferol level improved significantly (17.0 vs. 42.5 ng/ml), as did the mean pain score (7.7 vs. 4.2) and mean JOA back score (7.6 vs. 11.1). Seven of the patients had a pain score of <6 and a JOA back score of >10, the remaining 2 patients had neurological deficits and only slight improvement. CONCLUSION: Vitamin D supplementation may be used as an adjuvant treatment for patients with failed back surgery syndrome.