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.

Primary central nervous system lymphoma as a neurosurgical problem.

Primary central nervous system lymphoma (PCNSL) comprises around 3-5% of primary central nervous system (CNS) tumours and around 1% of all non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the most common histological type. High effectiveness of chemo- and radiotherapy for PCNSL regrettably does not eliminate significant risks of recurrence for CNS tumours. That results in higher interest in other treatment options, including surgical procedures. PCNSL remains in the scope of interest for many specialists and neurosurgeons seem to play a more important role.

Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis.

BACKGROUND: A better understanding of immune response in breast cancer brain metastases (BCBM) may prompt new preventive and therapeutic strategies. METHODS: Immunohistochemical expression of stromal tumor-infiltrating lymphocytes (TILs: CD4, CD8, CTLA4), macrophage/microglial cells (CD68), programmed cell death protein 1 receptor (PD-1), programmed cell death protein 1 receptor ligand (PD-L)1, PD-L2 and glial fibrillary acid protein was assessed in 84 BCBM and their microenvironment. RESULTS: Median survival after BCBM excision was 18.3 months (range 0-99). Median number of CD4+, CD8+ TILs and CD68+ was 49, 69 and 76 per 1 mm(2), respectively. PD-L1 and PD-L2 expression in BCBM was present in 53 % and 36 % of cases, and was not related to BCBM phenotype. PD-1 expression on TILs correlated positively with CD4+ and CD8+ TILs (r = 0.26 and 0.33), and so did CD68+ (r = 0.23 and 0.27, respectively). In the multivariate analysis, survival after BCBM excision positively correlated with PD-1 expression on TILs (hazard ratio (HR) = 0.3, P = 0.003), CD68+ infiltration (HR = 0.2, P < 0.001), brain radiotherapy (HR = 0.1, P < 0.001), endocrine therapy (HR = 0.1, P < 0.001), and negatively with hormone-receptor-negative/human epidermal growth factor receptor 2 (HER2)-positive phenotype of primary tumor (HR = 2.6, P = 0.01), HER2 expression in BCBM (HR = 4.9, P = 0.01). CONCLUSIONS: PD-L1 and PD-L2 expression is a common occurrence in BCBM, irrespective of primary tumor and BCBM phenotype. Favorable prognostic impact of PD-1 expression on TILs suggests a beneficial effect of preexisting immunity and implies a potential therapeutic role of immune checkpoint inhibitors in BCBM.

Aggressive behavior as a rare side effect of subthalamic stimulation in Parkinson's disease.

Although deep brain stimulation (DBS) has a well-established position in the treatment of Parkinson's disease (PD), it may be accompanied by different side effects including behavioral changes. We present a patient with advanced PD after bilateral stimulation of the subthalamic nucleus (STN) who developed attacks of aggressive behavior. The patient with a 12 year history of PD underwent the procedure of DBS with one-stage bilateral stereotactic approach using the Leksel G stereotactic frame. For STN identification microrecording technique was applied (5 microelectrodes). Four weeks after surgery STN stimulation was switched on. With increasing the amplitude of stimulation on the right (active contacts 1 and 2) the patient experienced transient episodes of aggression. Change of stimulation mode led to withdrawal of all side effects. We hypothesize that aggression episodes in the patient were caused by stimulation of limbic circuit probable within STN although we cannot exclude simultaneous stimulation of neighboring structures. Aggression episodes are rare side effect of STN-DBS, nevertheless they may be expected in more posteromedial placement of the electrode within STN. The presented case extends the evidence for non-motor functions of STN and highlights its role as an integrating structure within the basal ganglia system.

Effects of Therapy in Patients Suffering from Chronic Back Pain Treated with Spinal Cord Stimulation.

Pain in the lumbosacral part of the spine in the course of degenerative disease is the most common cause of physical activity limitation in adults. Treatment includes pharmacotherapy, physiotherapy, psychotherapy, health promotion, and sometimes surgery. Surgical treatment is not always successful, and the various clinical and psychosomatic symptoms that result from surgical treatment failure are known as failed back surgery syndrome. For some patients with this condition, spinal cord stimulation can provide relief. The aim of the work was to define subjective and objective spinal cord stimulation effects by assessing chosen disability and physical activity limitation ratios. Pain intensity, level of disability, and presence of neurological symptoms were assessed. The examination was performed twice: before the stimulator implantation and at least 6 months postimplantation. The study was conducted at the Department of Neurosurgery and Paediatric Neurosurgery in Lublin. Thirty-six patients suffering from failed back surgery syndrome were recruited for this study. The Visual Analog Scale, modified Laitinen's pain questionnaire, and Oswestry Disability Index were used in this work. The study showed that spinal cord stimulation was effective in treating spinal and lower limb pain in 64% of patients, similar to results obtained in other departments. Although back pain and neuropathic pain radiating to the lower limbs decreased, moderate physical activity impairment was still observed according to the Oswestry Disability Index scale. The decrease in neuropathic pain radiating to the lower limbs had the most significant influence on reducing physical activity impairment.

Preoperative neutrophil-lymphocyte count ratio helps predict the grade of glial tumor - a pilot study.

UNLABELLED: Neutrophil-lymphocyte count ratio (NLCR) is a recognized prognostic marker for renal, lung or colorectal carcinomas. The aim of the present study was to determine whether the preoperative value of NLCR might serve as a predictive marker for glial tumors' grading. METHODS: The retrospective analysis of NLCR was performed in neurosurgical patients treated for glial brain tumors. The preoperative NLCR was analyzed in accordance with WHO glial tumors' classification, which distinguishes G1, G2, G3 and G4 (glioblastoma) tumors. RESULTS: The analysis of NLCR was performed in 424 patients (258 males and 166 females) aged 53 ± 16 years who underwent either an open surgery or stereotactic biopsy for a glial brain tumor. G1 was diagnosed in 22 patients, G2 - in 71 patients, G3 - in 63 patients and G4 - in 268 patients. The highest value of NLCR was noted in G4 patients (5.08 [3.1; 8.7] - median [quartiles 1 and 3, respectively]) and was significantly higher compared to G3 (p<0.01), G2 (p<0.001) and G1 (p<0.01) groups. Moreover, NLCR was significantly higher in group G3 than G2 (p<0.05). ROC curve analysis showed 2.579 as a cut-off point for prediction of glioblastoma. CONCLUSION: Preoperative NLCR measurement corresponds with a glial brain tumor grading.

Astrocytoma malignum in glioblastoma multiforme vertens with long term survival--case report and a literature review.

Glioblastoma multiforme is the most common and most lethal pri- mary malignant tumor of the central nervous system. It can develop as a primary tumor or by transformation from its precursor--anaplastic astrocytoma which occurs less frequently but the prognosis is also unfavorable. Authors report a case of a 36-year-old man with "astrocytoma malignum in glioblastoma multiforme vertens" in the left frontal lobe. The mass, around 5 cm in diameter was resected by craniotomy 8 years ago. The patient received adiuvant radiation therapy concomitanly with temozolomide. He still stays asymptomatic, with no focal neurologic defects. There is no recurrence in the magnetic resonance imaging.

Efficacy of concomitant and adjuvant temozolomide in glioblastoma treatment. A multicentre randomized study.

BACKGROUND AND PURPOSE: The common treatment in patients with newly diagnosed glioblastoma multiforme is the ultimately radical surgical removal of the tumour combined with radiotherapy. This study compared safety and efficacy of radiotherapy alone with radiotherapy combined with temozolomide (TMZ) given before, during, and after radiotherapy. MATERIAL AND METHODS: The patients operated on for glioblastoma multiforme during the first 21 postoperative days were randomly assigned to the group treated with radiotherapy alone (involved-field radiotherapy in 2 Gy fractions daily five times a week up to the total of 60 Gy over 6 weeks of treatment) or to the group treated with radiotherapy and TMZ, initially in the dose of 200 mg/m² during 5 postoperative days and after 23 days followed by 75 mg/m2 of body surface area daily, 7 days a week (from the first to the last day of radiotherapy). On completion of radiotherapy, five complementary courses of TMZ were introduced (150-200 mg/m² for 5 days, repeated every 28 days). The primary outcome measure was overall survival. RESULTS: Fifty-eight patients from 3 centres were included in the study. The mean age of patients was 55 years and all the patients underwent a surgical procedure of glioblastoma removal. The mean overall survival in the group treated with TMZ was 16.0 months, whereas in the group with radiotherapy alone the overall survival reached 12.5 months. 24-month survival reached 23% in patients treated with TMZ and 6.7% in those who received radiotherapy only. Haematological complications of third or fourth degree were present in 10% of patients treated with radiotherapy and TMZ. CONCLUSIONS: The introduction of TMZ before, during and after radiotherapy for newly diagnosed glioblastoma multiforme gives clinically and statistically significant improvement of survival with unremarkably increased toxicity of the treatment.

The presence of HER2 exon 20 insertion in patients with central nervous system metastases from non-small lung cancer--a potential application in classification for therapy.

INTRODUCTION: HER2 (ErbB2/neu) is a member of the ErbB family of four structurally related receptors of tyrosine kinase activity. Overexpression of ErbB-1 (EGFR) and HER2 is found in many human cancers, but the presence of these genes mutations determines the effectiveness of EGFR and HER2 tyrosine kinase inhibitors in the therapy of non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: To search for insertions of the HER2 gene in exon 20 in 150 brain metastases of non-small cell lung cancer patients, we used a PCR technique based on analysis of amplified DNA fragment lengths. We also compared the HER2 mutational status with clinicopathologic features and the presence of EGFR and BRAF mutations. RESULTS: HER2 mutation was present in one male, non-smoking patient with low differentiated adenocarcinoma (0.67% of all patients and 1.5% of patients with adenocarcinoma). The mutations of EGFR and BRAF genes were not found in HER2-mutated patient. CONCLUSIONS: The literature data suggests that patients with HER2 mutations may be sensitive to tyrosine kinase inhibitors of both EGFR and HER2 receptors (e.g. afatinib). Therefore, the identification of new driver mutations in NSCLC can improve the quality of patient care by enabling the use of correct molecularly targeted therapies.

Conversion of epidermal growth factor receptor 2 and hormone receptor expression in breast cancer metastases to the brain.

INTRODUCTION: We investigated the status of estrogen receptor alpha (ERα), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) in primary tumor and in the corresponding brain metastases in a consecutive series of breast cancer patients. Additionally, we studied factors potentially influencing conversion and evaluated its association with survival. METHODS: The study group included 120 breast cancer patients. ERα, PR, and HER2 status in primary tumors and in matched brain metastases was determined centrally by immunohistochemistry and/or fluorescence in situ hybridization. RESULTS: Using the Allred score of ≥ 3 as a threshold, conversion of ERα and PR in brain metastases occurred in 29% of cases for both receptors, mostly from positive to negative. Conversion of HER2 occurred in 14% of patients and was more balanced either way. Time to brain relapse and the use of chemotherapy or trastuzumab did not influence conversion, whereas endocrine therapy induced conversion of ERα (P = 0.021) and PR (P = 0.001), mainly towards their loss. Receptor conversion had no significant impact on survival. CONCLUSIONS: Receptor conversion, particularly loss of hormone receptors, is a common event in brain metastases from breast cancer, and endocrine therapy may increase its incidence. Receptor conversion does not significantly affect survival.

Epidermal Growth Factor Receptor and its Oncogenic EGFRvIII Variant in Benign and Malignant Brain Tumors.

BACKGROUND/AIM: Tumorigenesis and cancer progression might be driven by abnormal activation of growth factor receptors. Importantly, molecular changes in EGFR-dependent signaling is one of the most common characteristics of brain tumors. PATIENTS AND METHODS: HER1 and EGFRvIII variants in meningiomas and glioblastomas were evaluated at the RNA level. RESULTS: EGFRvIII was found in 18.6% of glioblastomas (GBM), whereas 25% of EGFRvIII positive tumors express wild-type EGFR as well. HER1 was over-expressed in benign meningiomas compared to glioblastomas, whereas HER1 expression in meningiomas differed significantly between sub-types of meningiomas. EGFRvIII and HER1 where positively correlated in glioblastomas. Yet, the patient overall survival did not differ between high- and low-HER1 expressing glioblastomas or between EGFRvIII positive and negative GBMs. CONCLUSION: HER1 may be considered as an independent factor for classification of benign meningiomas. The mRNA levels of HER1 or EGFRvIII should not be used as independent prognostic factors for patients with gliomas.

Prophylactic use of dural tenting sutures in elective craniotomies in adults-is it necessary? A study protocol for a multicentre, investigator- and participant-blinded randomised, parallel-group, non-inferiority trial.

BACKGROUND: In the early days of neurosurgery, extradural haemorrhages (EDHs) contributed to a high mortality rate after craniotomies. Almost a century ago, Walter Dandy reported dural tenting sutures as an effective way to prevent postoperative EDH. Over time, his technique gained in popularity and significance to finally become a neurosurgical standard. Yet, several retrospective reports and one prospective report have questioned the ongoing need for dural tenting sutures. Dandy's explanation that the haemostasis observed under hypotensive conditions is deceiving and eventually causes EDH may be obsolete. Today, proper intra- and postoperative care, including maintenance of normovolemia and normotension and the use of modern haemostatic agents, may be sufficient for effective haemostasis. Thus, there is a fundamental need to evaluate the necessity of dural tenting sutures in a solid, unbiased, evidence-based manner. METHODS: This study is designed as a randomised, multicentre, double-blinded, controlled interventional trial with 1:1 allocation. About one half of the participants will undergo craniotomy without dural tenting sutures and will be considered an intervention group. The other half will undergo craniotomy with these sutures. Both groups will be followed clinically and radiologically. The primary outcome is reoperation due to extradural haematoma. Secondary outcomes aim to evaluate the impact of dural tenting sutures on mortality, readmission risk, postoperative headaches, size of extradural collection, cerebrospinal fluid leak risk and the presence of any new neurological deficit. The study protocol follows the SPIRIT 2013 statement. DISCUSSION: It is possible that many neurosurgeons around the globe are tenting the dura in elective craniotomies which brings no benefit and only extends the operation. Unfortunately, there is not enough data to support or reject this technique in modern neurosurgery. This is the first study that may produce strong, evidence-based recommendations on using dural tenting sutures. TRIAL REGISTRATION, ETHICS AND DISSEMINATION: The Bioethics Committee of the Medical University of Warsaw approved the study protocol (KB/106/2018). The trial is registered at http://www.clinicaltrials.gov ( NCT03658941 ) on September 6, 2018. The findings of this trial will be submitted to a peer-reviewed neurosurgical journal. Abstracts will be submitted to relevant national and international conferences. TRIAL STATUS: Protocol version and date: version 1.5, 14.01.2020 First recruitment: September 7, 2018 Estimated recruitment completion: September 1, 2021.

Langerhans cell histiocytosis of the parietal bone with epidural and extracranial expansion - case report and a review of the literature.

Langerhans cell histiocytosis is a rare neoplasm that belongs to the histiocytic and dendritic cell neoplasm group according to the 2008 WHO classification. It has been defined as neoplastic proliferation of Langerhans cells that express CD1a and S-100 proteins and have Birbeck granules on the ultrastructural examination. Clinical presentation and behaviour are heterogeneous and can range from a solitary lytic bone lesion with a favourable course to a fatal disseminated leukaemia-like form, with a wide spectrum of intermediate clinical presentations between these two extremes. Here, we present a case report of a solitary calvarial lesion in an adolescent boy along with a review of the literature. Presenting features, initial diagnostic evaluation and treatment protocol of a unifocal monosystemic calvarial location of LCH are presented.

Examination of marketing mix performance in relation to sustainable development of the Poland's confectionery industry.

The conventional concept of marketing mix does not take into account the idea of sustainable development. The basic objective of this examination is to analyze and evaluate the performance of selected marketing mix elements from the perspective of the Poland's confectionery industry's sustainable development. The questionnaire survey was designed for this purpose. The purpose of the research questions was to evaluate a degree of development for selected elements of marketing mix from the perspective of sustainable development of the Poland's confectionery industry. Thus, a novel development ratio based on the distance from exemplary performance was proposed. Next, aseminal approach to pairwise comparisons technique was applied for the importance evaluation of each survey question in order to provide a weighted average Mean Development Ratio (MdeR) for each element of marketing mix. In this process the seminal methodology for pairwise comparisons was applied i.e. a non-heuristic approach to pairwise comparisons technique with verifiable accuracy and reliability. In consequence, assuming that all elements of marketing mix have some designated importance in the process of sustainable development, a total weighted average MdeR for performance of all elements of marketing mix was computed and evaluated. Noticeably, the total weighted average MdeR for performance of all elements of marketing mix cannot be considered as satisfactory from the perspective of sustainable development of the Poland's confectionery industry.

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.

A Case Report of a Female Patient With Hodgkin Lymphoma Localized in the Central Nervous System and With Concomitant Pulmonary Lymphomatoid Granulomatosis.

The involvement of the central nervous system (CNS) in Hodgkin lymphoma (HL) has been rarely reported, especially in its primary isolated form. Herein, we present a case of a 33-year-old woman, who received immunosuppressive treatment due to ulcerative colitis (at the beginning azathioprine and sulfasalazine, changed to mesalazine), with repetitive episodes of loss of consciousness for a few weeks and with no other symptoms. Magnetic resonance imaging scans of the head revealed a tumor in the lateral part of the left temporal lobe and in the cerebellum. Moreover, a subsequent computed tomographic scan of the chest revealed diffuse tumorous lesions in the lungs. The brain tumor was resected and a tumorous lesion resected from the lungs was biopsied. The histopathological analysis confirmed the final diagnosis of HL localized in the CNS with concomitant pulmonary lymphomatoid granulomatosis (LYG) grade 1. After the patient underwent radiotherapy and chemotherapy, the patient showed complete regression of lesions in the CNS and lungs, which was confirmed by positron emission tomographic scan. LYG and CNS-HL are rare proliferative disease derived from lymphocytes B and associated with EBV infections. An association between LYG and other autoimmune disorders has been reported, but to the best of our knowledge, this is the first case of the CNS-HL associated with lymphatoid granulomatosis.

Treatment of very large cranial defects with individually shaped polypropylene polyester knitwear prostheses: a series of 11 cases.

BACKGROUND: Very large cranial defects are not very common in neurosurgical practice and there is not any widely acknowledged standard of their treatment. One of the useful methods in such cases is individual forming of polypropylene-polyester knitwear. Such material was used in the past but before 2008 it was available only as standardized plates. Currently, it can be also produced as individually-shaped implants. The authors give their definition of very large cranial defects and present their experience with this cranioplastic method in such defects. METHODS: The authors collected data on 11 cases of patients with very large cranial defects, from a total of 156 cases, operated on in 5 Polish neurosurgical departments. The necessary implants were prepared for individual patients according to the data provided by a computed tomography examination and with the use of computer aided machining. RESULTS: All defects were larger than 120 cm2 (129 to 178 cm2) and exceeded 1/4 of the calvaria area. Patients were operated between 2008 to 2012. In all patients, a very good aesthetic result and correct skull reconstruction was achieved. The follow-up time in all cases exceeded 1 year and reached 4 years in one case. No complications were observed. CONCLUSIONS: Individually pre-shaped polypropylene-polyester knitwear prostheses are a good alternative to the existing cranioplasty methods, particularly in very large cranial defects.

Inhibition of respiratory processes by overabundance of zinc in neuronal cells.

Studies suggest that excessive amounts of free zinc ions can cause neuron death by interfering with the energy production process. The sites of the cell oxidation activity of zinc are the glycolytic enzymes, the Krebs cycle components and the respiratory chain. Further consequences of reduced access to energy are: increased production of reactive forms of oxygen, decrease of the mitochondrial membrane potential and decreased level of ATP. Also, the toxicity of zinc accelerates the supply of extra amounts of this element to the mitochondria, which results in their increased permeability.

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.