Altered serum cytokines in patients with symptomatic disk herniation and depressive symptoms.

Purpose: An increasing number of studies have indicated the important role of cytokines in the development of depressive disturbances (DD). In medically ill patients, cytokines can provoked sickness behavior, the signs of which resemble DD. This results in alterations in behavior to limit energy expenditure and redirect it to cope with particular diseases. The aim of our study was to investigate the role of pro-inflammatory IL-6, TNF-α, and IL-1ß and anti-inflammatory IL-10 and TGF-ß in DD observed in patients suffering from pain caused by disk herniation (DH) qualified for surgery. Patients and methods: The intensity of DD assessed by using Beck Depression Inventory, pain intensity, and functional impairment were evaluated in 70 patients with DH who were qualified for surgery. Pro-inflammatory serum levels of TNF-α, IL-1, IL-6, anti-inflammatory TGF-ß, and IL-10 were measured. Results: Elevated serum levels of TGF-ß, IL-10, and IL-6 were found in the group with moderate and severe depressive symptoms (SD) compared with the groups with mild (MD) or no depressive symptoms (ND). TGF-ß levels were negatively correlated with pain intensity, as assessed using the Present Pain Intensity scale in SD. Functional impairment measured using the Oswestry Disability Index was the most advanced in SD group. Conclusion: Results of our study can suggest association between depressive disturbances and anti-inflammatory cytokines TGF-ß and IL-10. Functional impairment of SD group is more severe but serum levels of TGF-ß and IL-10, which are involved in the healing processes, are increased.

Metalloproteinase-2 in failed back surgery syndrome caused by epidural fibrosis: can it play a role in persistent pain?

Purpose: Failed Back Surgery Syndrome (FBSS) occurs in 10-40% of patients treated surgically due to disk herniation (DH). There are several factors that can cause a predisposition to FBSS, but the exact pathomechanism has not been elucidated. The aim of this study was to investigate Metalloproteinase-2 (MMP-2) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) activities in a homogeneous group of FBSS patients with epidural fibrosis in comparison to its activity in patients with surgically treated DH. Methods: DH, FBSS, and control (CG) groups consisted of 30 subjects. The patients were assessed clinically by the Numerical Rating Scale (NRS), McGill Pain Questionnaire (SF -MPQ), Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). Serum concentrations of MMP-2 and TIMP-2 were measured by using the immunoenzymatic method. Results: There was a significantly higher MMP-2 expression (medians: 4797.49 vs. 2656.65; p < 0.0001) and TIMP-2 concentration (medians: 166.40 vs. 109.60; p < 0.0001) in the DH compared to the CG. Significantly higher MMP-2 expression (4219.95 vs. 2656.65; p < 0.0001) and TIMP-2 concentration (medians: 150.17 vs. 109.60; p = 0.0003) were also found in the FBSS compared to the CG. The activity of MMP-2, measured as MMP-2/TIMP-2, did not significantly change between the DH, FBSS, and CG. MMP2 expression (p < 0.0001) and TIMP-2 concentration (p < 0.0001) were significantly higher in the DH than FBSS. Conclusion: Results indicate the presence of a contribution of MMP-2 and TIMP-2 in DH and FBSS. Unchanged activity of MMP-2 can indicate an insufficiency in the MMP-2 repair system in both diseases. Lower MMP-2 expression and TIMP-2 concentration in the FBSS group can reflect the chronicity of the process.

VAS and NRS, Same or Different? Are Visual Analog Scale Values and Numerical Rating Scale Equally Viable Tools for Assessing Patients after Microdiscectomy?

Objectives: To compare the viability of the numerical rating scale (NRS) and the visual analogue scale (VAS) as a pain assessment tools among a large cohort of patients who underwent microdiscectomy. Summary of Background Data. The pain intensity (PI) reduction is a parameter of surgical treatment efficacy. The two most commonly used scales of PI are NRS and VAS. Many studies have shown strong similarities between those two scales, but the direct interchange is difficult. Methods: Patients, who underwent microdiscectomy, were prospectively enrolled into the study and assessed using VAS and NRS for the back (NRS-B) and the leg (NRS-L), Short Form of McGill Pain Questionnaire (SF-MPQ) included Pain Rating Index (PRI) and Oswestry Disability Index (ODI) 1 day before and 1 month and 3 months after the procedure. Results: 131 patients were included in the study. NRS-L, NRS-B, VAS, and ODI were significantly lower (p < 0.001) 1 month after microdiscectomy. NRS-L and NRS-B ratings remained at a similar level while VAS and ODI decreased after 3 months. The rate of decline of PI measured by NRS-L correlated statistically significant (rs = 0.366; p < 0.001) with ODI 1 month after surgery. Before surgery, the most significant correlation was found between ODI and NRS-L (rs = 0.494; p < 0.001), the lowest with NRS-B (rs = 0.319; p < 0.001). 3 months after surgery, there was higher correlations between ODI and VAS (rs = 0.634) than NRS-L (rs = 0.265). PRI correlated significantly (p < 0.001) and more stronger with VAS than with NRS-L and NRS-B in every points of assessment. Conclusion: The results showed that PI measurements by NRS-L/NRS-B and VAS mutually correlate and impair functionality evaluated by ODI (convergent validity) but in different modes (differential validity). NRS and VAS are not parallel scales and assess different aspects of pain. The measurement of NRS-L 1 month after microdiscectomy seems to give quick insight into the effectiveness of the procedure.

IFN-γ Correlations with Pain Assessment, Radiological Findings, and Clinical Intercourse in Patient after Lumbar Microdiscectomy: Preliminary Study.

OBJECTIVES: We investigated the influence of pain decrease after lumbar microdiscectomy on the interferon gamma (IFN-γ) serum level in patients with lumbar disc herniations. The study challenges the mechanism of sciatica pain and the role of IFN-γ in radicular pain development. Material and Methods. We performed clinical and immunoenzymatic assessment in a group of 27 patients with lumbar radicular pain due to disc herniations before and 3 months after surgery. Clinical status was assessed with the use of the Numeric Rating Scale (NRS), the Pain Rating Index and Pain Intensity 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 observe significant correlations between the results of the pain in the back region assessment NRS back scale after the surgery with the level of IFN-γ before the procedure (r s = 0.528; p = 0.008) and after the procedure (r s = 0.455; p = 0.025). These are moderate and positive correlations-the decrease in pain is correlated with the lower IFN-γ level. Additionally, there are significant correlations between the results of the PRI scale and the IFN-γ level. The PRI score before surgery correlates positively with IFN-γ after surgery (r s = 0.462; p = 0.023), and the PRI score after surgery correlates positively with IFN before surgery (r s = 0.529; p = 0.005) and after surgery (r s = 0.549; p = 0.003). All correlations are moderate in severity-severe pain before surgery correlates with a higher level of IFN-γ after surgery and also higher IFN-γ before surgery. There were significant differences in the IFN-γ level before (Z = -2.733; p = 0.006) and after (Z = -2.391; p = 0.017) surgery in the groups of patients with and without nerve compression. In the group of patients with nerve compression, the level of IFN-γ before and after surgery was lower. CONCLUSIONS: Less pain ratio after operation correlates with the level of IFN-γ. In the group of patients without significant nerve compression confirmed by MRI scans, the level of IFN-γ before and after surgery was higher than that in the group with nerve root compression.

The impact of changes in serum levels of metalloproteinase-2 and metalloproteinase-9 on pain perception in patients with disc herniation before and after surgery.

Purpose: The aim of our research was to investigate the link between serum levels of metalloproteinase-2 (MMP-2) and MMP-9, and the degree of pain experienced before and 1 and 3 months after microdiscectomy in 70 patients with disc herniation (DH). Patients and methods: The control group (group C) consisted of 70 healthy subjects and the DH group consisted of 70 patients with sciatica pain caused by lumbar DH. Before (DH0) and 1 and 3 months after surgery, the patients were assessed in terms of the following biochemical parameters: MMP-2, tissue inhibitors of metalloproteinases-2 (TIMP-2), MMP-2/TIMP-2, MMP-9, TIMP-1, and MMP-9/TIMP1, and the following clinical parameters: Numeric Rating Scale for the back (NRS-B) and the leg (NRS-L) and the Pain Rating Index (PRI) and Present Pain Intensity (PPI) of the McGill Pain Questionnaire. Results: No statistically significant correlations were observed following the biochemical and clinical assessments performed in group C and the DH group before surgery. After surgery (1 month), higher levels of TIMP-1 correlated with higher levels of NRS-B (rs =0.27; p<0.05). At 3 months after surgery higher levels of TIMP-2 and lower levels of MMP-2/TIMP-2 were correlated with higher levels of NRS-L (rs =0.27, p<0.05 and rs =-0.31, p<0.05, respectively) and higher levels of TIMP-2 were correlated with higher PRI scores (rs =0.27; p<0.005) and PPI scores (rs =0.35; p<0.01). Conclusion: The results showed that MMPs are involved in DH and play a significant role in the perception of pain after DH surgery. However, the value of MMPs as a potential therapeutic target in pain treatment should be considered cautiously.

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.

Assessment of explicit and implicit linguistic impairments in patients with aphasia after resection of tumour of the left cerebral hemisphere. Preliminary results.

BACKGROUND AND PURPOSE: Classical definitions of aphasia des-cribe deficits of different language levels (syntactic, semantic, phonologic) hindering the ability to communicate. Recent studies indicate, however, that impairment of particular aspects of linguistic competencies in aphasia differs in severity. Contemporary approach to the aphasic symptoms presents them as disturbed access of linguistic representations to the awareness system. Accordingly, such an approach requires different types of tasks: direct, involving explicit language processes, and indirect, based on implicit language representations. The aim of our study was to examine explicit and implicit language processes in patients with aphasia after resection of the tumour of left cerebral hemisphere along with characterization of relationships between explicit and implicit language processes. MATERIAL AND METHODS: Our cohort included 28 right-handed patients who were divided into four equal groups: two clinical (brain tumours) and two control (lumbar disc disease). Four tasks that assess and compare language processes: lexical decisions (at explicit and implicit levels), sorting of picture captions and word monitoring were implemented. RESULTS: In direct tasks, patients with aphasia provided less correct lexical decisions at word level, but did not show deficits in sentence comprehension. In both groups, no priming effect was observed in tasks requiring implicit lexical decisions. The longest time was found in non-primed words, the shortest in pseudowords. The differences between groups regarding word monitoring were also observed. Patients with aphasia obtained longer reaction times in all types of sentences (of different grade of language correctness), with respect to low- and high- frequency words. CONCLUSIONS: Patients with aphasia after brain tumour resection show more pronounced impairments of explicit than implicit linguistic behavior; the same effect was found in studies on forgetting in amnestic syndrome.