Treatment Of Chronic Pain Syndromes Research Articles

Neuroplasticity in the pathogenesis and treatment of chronic pain syndrome: new research and therapeutic perspectives

Recent research and therapeutic outlooks examine the impact of neuroplasticity on the progression and management of chronic pain syndrome. Aims: To review neurobiological basis as well as neuroplastic mechanisms in chronic pain syndrome, exploring bidirectional relationship and innovative therapies and to evaluate efficacy/safety of diverse treatments like TENS, rTMS, pharmacotherapies, and exercise in chronic pain management. Study design: A narrative literature review. Place and Duration of Study: 2019 to 2024. Methodology: A narrative review was conducted using the keywords “Neuroplasticity" AND "Chronic Pain" on PubMed yielded a total of 333 publications. Out of the total publications, 21 were deemed directly relevant, probably providing valuable perspectives on the link between neuroplasticity and chronic pain. Results: Results showed that out of the 11 studies analysed, 7 investigated the bidirectional relationship between chronic pain and neuroplasticity. Additionally, 4 studies reviewed pharmacological methods, 2 studies discussed personalised management and mechanistic profiling, and 7 explored neuromodulation and non-pharmacological interventions. Various neurophysiological correlates of chronic pain were studied, including somatosensory and cortical neurophysiology profiles but Central sensitisation and neuroinflammation were the explored key mechanisms. Activity-dependent plasticity, neuroplasticity in pain modulation, and cortical plasticity are extensively explored, revealing changes in neural activity, synaptic strength, and brain structure. Research explores the connection between chronic pain and neuroplasticity, examining how they impact each other and highlighting the constant interaction between pain perception and neural plasticity. Innovative therapeutic strategies include neuromodulation techniques, pharmacological interventions, personalised pain management, and multimodal approach. Non-invasive brain stimulation, transcutaneous electrical nerve stimulation , and home-based focused tDCS show promise in chronic pain management. Conclusion: In summary, these findings highlighted the multifaceted nature of chronic pain and the on-going efforts to develop effective therapeutic interventions, showcasing a dynamic field of research aiming to improve the lives of those suffering from chronic pain.

Problems of diagnosis and treatment of chronic pain syndrome in patients with variants of the structure of peripheral nerves. A series of clinical cases

AIM: To assess the presence of variants of the structure of peripheral nerves as possible risk factors for chronic pain syndrome on the example of a series of clinical cases.
 MATERIALS AND METHODS: The systematization and analysis of data from domestic and foreign literature on pathophysiology, clinic, diagnosis and treatment of complex regional pain syndrome has been carried out. Research method: system analysis, presentation of a series of clinical cases.
 RESULTS: A series of clinical cases is presented. The main risk factors for chronic pain syndrome are presented. The conditions and diseases that need to be differentially diagnosed if complex regional pain syndrome is suspected are systematized: tunnel syndromes (carpal tunnel syndrome), diabetic polyneuropathy, HIV polyneuropathy, postherpetic neuralgia, neurogenic claudication/lumbar stenosis, central post-stroke pain, upper thoracic syndrome apertures.
 CONCLUSION: Today, practitioners and neurophysiologists are not sufficiently aware of the existence of interneural anastomoses and features, typical electroneuromyographic signs, as a result of which in most cases the obtained electroneuromyographic data are interpreted erroneously. Variants of the structure of nerves can give an incorrect clinical picture of the condition of peripheral nerves and lead to untimely diagnosis and treatment of chronic pain syndrome, complex regional pain syndrome. Improvements in diagnostic methods, as well as widely introduced high-tech examination methods, in particular electroneuromyography, magnetic resonance imaging and ultrasound, are helping to increase the frequency of detection of abnormalities in the structure of peripheral nerves. In the presented clinical cases, patients had structural variants that gave an incorrect clinical picture of the condition of the peripheral nerves and led to untimely diagnosis and treatment — the development of chronic pain syndrome.

Cryoablation of the adenohypophysis in the treatment of chronic pain syndrome in patients with stage IV malignant neoplasms

Background. The data of the European Society For Medical Oncology (ESMO) indicate that 64.0% of cancer patients with the fourth stage of cancer have chronic pain syndrome, which is the main factor that significantly affects the quality of life. In 46.0% of patients, it is not possible to obtain a stable analgesic effect with modern methods of analgesia, including interventional methods and pharmacotherapy. Refractory oncological pain stimulates the search for new methods of pain relief.
 Purpose – retrospective assessment of the effectiveness of the selective stereo- tactic transnasal transsphenoidal cryoablation of the adenohypophysis in the treatment of chronic pain syndrome in patients with stage IV malignant neoplasms.
 Materials and methods. 45 microsurgeries were performed – stereotactic selective transnasal transsphenoidal cryoablation of the adenohypophysis with endoscopy. Over the period from 2014 to 2018, 45 patients with stage IV malignant hormone- dependent neoplasms of various somatic organs and chronic pain syndrome underwent microsurgery.
 Results. The analgesic effect appeared 4–6 hours after the microsurgery. In 95.6% of patients, an analgesic effect was achieved to a greater extent (according to the numeric rating scale (NRS) for pain, its intensity decreased from 7–9 points to 1–3 points); in other patients, the analgesic effect was achieved to a lesser extent (according to the NRS, pain intensity decreased from 7–9 points to 3–5 points), regardless of the condition and age of the patient. Accordingly, the dosage was reduced or opioid analgesics were discontinued. Severe complications after the cryoablation of adenohypophysis, such as meningitis, diabetes insipidus, and hypopituitary syndrome were not observed. In the postoperative period, three patients were treated for mild hypopituitary syndrome, and two patients were treated for liquorrhea with conservative therapy for 3–5 days.
 Conclusions. Stereotactic selective transnasal transsphenoidal cryoablation of the adenohypophysis is an effective microsurgery in the treatment of chronic pain syndrome in stage IV cancer patients. It improves the patient’s condition and quality of life. The analgesic effect appears in the first hours after surgery. Due to the use of cryoprobes with a diameter of 1.2 mm and 1.8 mm, the surgery is minimally traumatic and can be performed on patients in critical condition.

Analysis of social and economic aspects of using prolonged forms of opioid analgesics for the treatment of chronic pain syndrome in cancer patients

Analysis of social and economic aspects of using prolonged forms of opioid analgesics for the treatment of chronic pain syndrome in cancer patients

Celiac plexus neurolysis in treatment of chronic pain syndrome in patients with unresectable pancreatic cancer

Celiac plexus neurolysis in treatment of chronic pain syndrome in patients with unresectable pancreatic cancer

A novel recognition of artificial intelligence in regional anaesthesia

Mechanised analysis of algorithms for problem solving, object recognition and decision-making assistance defines the general concept underlining artificial intelligence (AI).[1] The former presents notable applications in perioperative medicine across diverse situations like depth of anaesthesia monitoring, closed-loop anaesthesia delivery, risk-predictive models, pain-management through objective analgo-scoring, operating-room planning logistics and, guidance of perioperative ultrasonography. The recent Food and Drug Administration (FDA) approval[2] of the Scan Nav™ Anatomy Peripheral Nerve Block (PNB) system (Intelligent Ultrasound Group, Cardiff, United Kingdom)[3] only emerges as a novel recognition of the potential of AI in regional anaesthesia. Worthwhile to mention, Hemmerling et al.[4] described an encouraging seminal use of the robotic ultrasound-guided nerve block system or the Magellan system, almost a decade ago. Employing the same system, Morse et al.[5] went on to compare the performance parameters (learning curve and success rates) and subjective performance variability of manual versus robot-assisted ultrasonographic nerve blocks in a phantom model. The authors found that assistance of nerve blocks, enabled significant faster needle guidance (1.8 [1.6] seconds vs. 0.3 [0.3] seconds; P = 0.007), than for manual blocks. Inter-subject performance variability was also found to be considerably attenuated. Specific to the context of the recently FDA approved software medical device, ScanNav™ Anatomy PNB system uses deep-learning AI technology. During performance of a peripheral nerve block the ScanNav™ system identifies and grades a live ultrasound image using this technology. A distinctive colour overlay of the key sono-anatomical structures during a live ultrasound scan is a characteristic valuable attribute of the system.[3] This enhances standardisation and accuracy of the ultrasound image interpretation. This device colour highlights anatomy of 10 vital regions relevant to ultrasound-guided regional anaesthesia namely Interscalene, Supraclavicular, Axillary and Superior Trunk Brachial plexus of the upper limb; Erector Spinae Plane, Rectus Sheath and Supra-inguinal Fascia Iliaca sheath of truncal structures; and Femoral Nerve, Adductor canal and Popliteal nerve sheath of the lower limb. Furthermore, a 3-dimension inbuilt reference material provides a review of the relevant anatomy, probe-positioning technique; and demonstrates a virtual scan of the selected anatomical region. The system enables adjustments in the intensity of coloured highlighting according to user preference and allows for viewing the unmodified and highlighted images side-by-side for better comprehension of the sono-anatomy. The use of ScanNav™ system thereby facilitates as a labelling device alongside real-time anatomy visualisation during regional anaesthesia. The system also has inbuilt virtual scans that assist the clinician functioning as a 3D reference material of the relevant PNB anatomy scanned. Notably so, the software is compatible with the general-purpose ultrasound systems in addition to being a stand-alone device. Talking of the literature relevant to the ScanNav™ Anatomy PNB system, Bowness et al.[6] compared 240 ultrasound scans performed across 15 expert versus non-expert regional anaesthesia providers on evaluating its' role in promoting the uptake and generalisability of ultrasound-guided regional anaesthesia. The authors outlined that non-experts were more likely to submit positive feedback and less likely to submit negative reviews than the experts (P = 0.001). Positive feedbacks were obtained on the role of the device in training (37/60, 61.7%) and utility for teaching (30/60, 50.0%). Meanwhile the non-experts appreciated the anatomic structure identification and learning, as the contextual benefits, some nonexperts and experts thought the device could decrease the scanning confidence. Additionally, expert providers reported a potentially increased, yet insignificant, risk in 12/254 (4.7%) vs. 8/254 (3.1%, P = 0.362) scans for needle trauma to “safety” structures. The discussion elaborates the tremendous opportunity AI has to offer in guiding regional anaesthesia, awaiting prospective validation outside the core 10 block areas. The utility of this device can be further extended to sympathetic blocks like the stellate-ganglion, celiac-plexus and other blocks for treatment of chronic pain syndromes like complex regional pain syndrome. The times might not be distant when perioperative physicians have routine access to ultrasound machines integrated with AI-assisted colour reframing for anatomical landmark “coding” side by side with the present B-mode, M-mode and colour/pulse Doppler profiling.

Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Mediates Chronic Pain and Cytokine Production in Mouse Models of Inflammatory, Neuropathic, and Primary Pain

The origin of chronic pain is linked to inflammation, characterized by increased levels of proinflammatory cytokines in local tissues and systemic circulation. Transforming growth factor beta-activated kinase 1 (TAK1) is a key regulator of proinflammatory cytokine signaling that has been well characterized in the context of cancer and autoimmune disorders, yet its role in chronic pain is less clear. Here, we evaluated the ability of our TAK1 small-molecule inhibitor, takinib, to attenuate pain and inflammation in preclinical models of inflammatory, neuropathic, and primary pain. Inflammatory, neuropathic, and primary pain was modeled using intraplantar complete Freund’s adjuvant (CFA), chronic constriction injury (CCI), and systemic delivery of the catechol-O-methyltransferase (COMT) inhibitor OR486, respectively. Behavioral responses evoked by mechanical and thermal stimuli were evaluated in separate groups of mice receiving takinib or vehicle prior to pain induction (baseline) and over 12 days following CFA injection, 4 weeks following CCI surgery, and 6 hours following OR486 delivery. Hindpaw edema was also measured prior to and 3 days following CFA injection. Upon termination of behavioral experiments, dorsal root ganglia (DRG) were collected to measure cytokines. We also evaluated the ability of takinib to modulate nociceptor activity via in vitro calcium imaging of neurons isolated from the DRG of Gcamp3 mice. In all 3 models, TAK1 inhibition significantly reduced hypersensitivity to mechanical and thermal stimuli and expression of proinflammatory cytokines in DRG. Furthermore, TAK1 inhibition significantly reduced the activity of tumor necrosis factor (TNF)-primed/capsaicin-evoked DRG nociceptive neurons. Overall, our results support the therapeutic potential of TAK1 as a novel drug target for the treatment of chronic pain syndromes with different etiologies. PerspectiveThis article reports the therapeutic potential of TAK1 inhibitors for the treatment of chronic pain. This new treatment has the potential to provide a greater therapeutic offering to physicians and patients suffering from chronic pain as well as reduce the dependency on opioid-based pain treatments.

Modern approaches in the treatment of oncological pain: surgical treatment

Based on the analysis of modern literature, surgical approaches to the treatment of chronic pain syndrome in cancer patients are presented. The definition and classification of chronic pain syndrome is given, its pathophysiology is described. The frequency of occurrence in the population and its dependence on the stage and localization of malignant neoplasm is shown. For practical use, an algorithm for the diagnosis of chronic pain syndrome and the basic principles of its therapy are presented. As the 4th step of the World Health Organization pain relief ladder, surgical methods for the treatment of chronic pain syndrome are separately considered. Three main types of surgical interventions (neuromodulating, neurodestructive and anatomical) are described, indications and contraindications to their use are indicated.

Analysis of changes in the serotonin inactivation coefficient in brain structures with simultaneous modeling of chronic neurogenic pain and malignant neoplasia

Introduction. Chronic pain syndrome in the development of malignant neoplasms has a complex polyethological character. The study of the pathogenetic mechanisms of pain during the growth of the transplanted tumor in the experiment can open up broad perspectives for the creation of new domestic analgesic drugs for use in oncology.Aim: To study the serotonin inactivation coefficient (SIC), the ratio of serotonin (S) and its main metabolite 5-hydroxyindolacetic acid (S-OH) in brain areas (cortex, hypothalamus) with simultaneous modeling of chronic neurogenic pain and malignant neoplasia.Material and Methods. The study involved white mongrel rats (males). To create a model of chronic pain (CP), ligation of the sciatic nerve was performed according to the method of V.V. Kravtsova in modification. Rat sarcoma M-1 was used to simulate malignant neoplasia. At the main stage of the study, the animals were divided into 4 groups: control, two comparison groups (model of chronic pain, standard M-1 sarcoma grafting) and experimental (combined modeling of CP and oncological process). Animals of the second, third and fourth groups were euthanized sequentially at the 2nd and 3rd weeks of the development of the tumor process.Results. Chronic pain syndrome disrupts the process of serotonin metabolism: the decrease in SIC in the cerebral cortex of experimental animals was more significant by 48% (day 14) and 72% (day 21). The development of the oncological process in comparison groups (groups 3a and 3b) is accompanied by a decrease in the level of SIC, more significant at the 21th day of M-1 sarcoma development: by 37% in the hypothalamus, by 41% in the cerebral cortex. With simultaneous modeling of chronic neurogenic pain and malignant neoplasia, the lowest values of the studied indicator were noted, the decrease was 75% in the cerebral cortex (group 4a) and 87% (group 4b).Discussion. Chronic neurogenic pain and M-1 sarcoma development in isolated modeling variants cause a significant decrease in SIC in hypothalamus and cerebral cortex due to disorders of serotonin formation. A more significant disruption of the serotonin mediator system was noted in cerebral cortex which leads to a decrease in the body’s adaptive capabilities to pain and a disruption of the regulatory mechanisms of metabolism.Conclusion. Modification of serotonin metabolism can be considered as a potential therapeutic target for the treatment of chronic pain syndrome in oncology.

Best Practices for Dorsal Root Ganglion Stimulation for Chronic Pain: Guidelines from the American Society of Pain and Neuroscience.

With continued innovations in neuromodulation comes the need for evolving reviews of best practices. Dorsal root ganglion stimulation (DRG-S) has significantly improved the treatment of complex regional pain syndrome (CRPS), and it has broad applicability across a wide range of other conditions. Through funding and organizational leadership by the American Society for Pain and Neuroscience (ASPN), this best practices consensus document has been developed for the selection, implantation, and use of DRG stimulation for the treatment of chronic pain syndromes. This document is composed of a comprehensive narrative literature review that has been performed regarding the role of the DRG in chronic pain and the clinical evidence for DRG-S as a treatment for multiple pain etiologies. Best practice recommendations encompass safety management, implantation techniques, and mitigation of the potential complications reported in the literature. Looking to the future of neuromodulation, DRG-S holds promise as a robust intervention for otherwise intractable pain.

Preliminary outcomes of the COVID-19 pandemic: a new chronic pain profile

In summing up the preliminary results of the COVID-19 pandemic that has not yet ended, modern research pays much attention to the so-called post-COVID syndrome, which includes the long-term consequences of the disease. In English, symptoms are reported as long COVID, post-acute COVID, or chronic post-COVID syndrome and are described as symptoms of fatigue, respiratory disorders, memory, and sleep problems. Symptoms such as muscle pain and decreased endurance when performing habitual physical exertion are mentioned much less often. Meanwhile, among the complaints of those who have been ill, this symptom is present quite often, reducing the quality of life and tolerability of normal physical exertion. This review aimed to provide an in-depth study of a new type of the chronic myofascial pain syndrome after COVID-19, i.e., the frequency of occurrence, causes of the development, and pathophysiology of chronic pain syndrome associated with COVID-19 and manifested as fibromyalgia of various localizations. To answer the questions posed, the authors searched for information in four electronic databases. The key search terms used were COVID-19, long COVID, and signs and symptoms of pain syndrome. A review of current literature data has shown that close study and dynamic monitoring of patients who had COVID-19 can contribute to further deciphering the pathophysiological mechanisms of the development of its long-term consequences and provide answers to questions on the prevention and treatment of chronic pain syndrome in this patient cohort.

The effectiveness of using “Painmetrica” software for the diagnosis and selection of treatment for chronic pain syndrome in degenerative diseases of the spine

Objective. To evaluate the effectiveness of using the “Painmetrica” software for the diagnosis and selection of treatment for pain in degenerative diseases of the spine. Materials and methods. Software “Painmetrica” was developed for the diagnosis and selection of treatment for pain in degenerative diseases of the spine. Through a bidirectional nonrandomized controlled trial, its effectiveness was evaluated using telephone interviews with 42 patients. For comparison, a telephone interview was conducted with 47 patients for whom the Panimetrica program had not been used in the treatment.Results. The effectiveness of using “Painmetrica” software for the diagnosis and selection of treatment for patients with back pain was demonstrated. In the main group, the decrease in pain syndrome tended to differ due to an increase in the number of patients in whom pain was relieved by more than 50% and completely disappeared (p = 0,09 according to the two-tailed Fisher’s exact test). Patients treated with Painmetrica algorithms experienced sleep recovery due to a decrease in pain: changes persisted in 12 cases (28,6%), while in the comparison group, sleep changes remained in 24 patients (51,1%) (p=0,05 according to two-tailed Fisher’s exact test). Against the background of effective pain relief in patients who used Painmetrica, there was a decrease in the use of non-steroidal anti-inflammatory drugs (NSAIDs) (17 patients (40,5%) of the main group versus 36 patients (76,6%) of the control group, p = 0,001 according to the twotailed Fisher’s exact test ). At the same time, only 8 patients (19.1%) in the main group and 30 patients (63.8%) in the comparison group (p < 0.001 according to Fisher’s two-sided exact test) indicated the need to consult a neurologist.Conclusion. The effectiveness of the use of “Painmetrica” software for the diagnosis and selection of treatment of patients with degenerative diseases of the spine on an outpatient basis in relation to the need for patients to use nonsteroidal anti-inflammatory drugs, the need for additional consultation of a neurologist, as well as effective relief of sleep disorders caused by pain were demonstrated.

Analysis of changes in the serotonin inactivation coefficient in brain structures with simultaneous modeling of chronic neurogenic pain and malignant neoplasia

Introduction. Chronic pain syndrome in the development of malignant neoplasms has a complex polyethological character. The study of the pathogenetic mechanisms of pain during the growth of the transplanted tumor in the experiment can open up broad perspectives for the creation of new domestic analgesic drugs for use in oncology.Aim. To study the serotonin inactivation coefficient (SIC), the ratio of serotonin (S) and its main metabolite 5-hydroxyindolacetic acid (S-OH) in brain areas (cortex, hypothalamus) with simultaneous modeling of chronic neurogenic pain and malignant neoplasia.Material and Methods. The study involved white mongrel rats (males). To create a model of chronic pain (CP), ligation of the sciatic nerve was performed according to the method of V.V. Kravtsova in modification. Rat sarcoma M-1 was used to simulate malignant neoplasia. At the main stage of the study, the animals were divided into 4 groups: control, two comparison groups (model of chronic pain, standard M-1 sarcoma grafting) and experimental (combined modeling of CP and oncological process). Animals of the second, third and fourth groups were euthanized sequentially at the 2nd and 3rd weeks of the development of the tumor process.Results. Chronic pain syndrome disrupts the process of serotonin metabolism: the decrease in SIC in the cerebral cortex of experimental animals was more significant by 48% (day 14) and 72% (day 21). The development of the oncological process in comparison groups (groups 3a and 3b) is accompanied by a decrease in the level of SIC, more significant at the 21th day of M-1 sarcoma development: by 37% in the hypothalamus, by 41% in the cerebral cortex. With simultaneous modeling of chronic neurogenic pain and malignant neoplasia, the lowest values of the studied indicator were noted, the decrease was 75% in the cerebral cortex (group 4a) and 87% (group 4b).Discussion. Chronic neurogenic pain and M-1 sarcoma development in isolated modeling variants cause a significant decrease in SIC in hypothalamus and cerebral cortex due to disorders of serotonin formation. A more significant disruption of the serotonin mediator system was noted in cerebral cortex which leads to a decrease in the body's adaptive capabilities to pain and a disruption of the regulatory mechanisms of metabolism.Conclusion. Modification of serotonin metabolism can be considered as a potential therapeutic target for the treatment of chronic pain syndrome in oncology.

Комбинированная терапия хронической боли при вертеброгенной патологии, возможности Пиаскледина (ASU) и тразодона

Статья посвящена различным видам вертеброгенных и мышечно-скелетных болевых синдромов. Особое внимание уделяется месту структурно-модифицирующих препаратов в комплексе лечения хронического болевого синдрома у данной категории больных, а также воздействию на психологические компоненты болевого синдрома, включая депрессию и тревогу.

Ефективність та доцільність застосування напроксену при різних клінічних ситуаціях

В оглядовій статті подано докази клінічної ефективності напроксену в лікуванні пацієнтів ревматологічного профілю. Сучасна концепція раціонального й безпечного застосування нестероїдних протизапальних препаратів (НПЗП) передбачає досягнення максимальної ефективності разом з максимальним зниженням ризику ускладнень, насамперед із боку серцево-судинної та гастроінтестинальної систем. За даними клінічних досліджень, серед усіх НПЗП найменший ризик кардіоваскулярних ускладнень відзначений у напроксену. Напроксен належить до групи неселективних НПЗП, активно використовується в клінічний практиці вже понад 40 років та завоював довіру лікарів як надійний анальгетик та протизапальний засіб. Терапевтичний потенціал напроксену доведений при різних клінічних ситуаціях — від гострих епізодів болю та запалення і до хронічного больового синдрому в ревматологічній практиці. У статті наведені та проаналізовані рандомізовані клінічні випробування, що підкреслюють клінічну ефективність та безпеку при застосуванні напроксену при гострому подагричному артриті, гострих травмах, остеоартриті, ревматоїдному артриті та спондилоартритах.

Поражение почек, ассоциированное с нестероидными противовоспалительными препаратами

The review is devoted to one of the important problems of the clinic of internal diseases - kidney damage associated with painkillers and main non-steroidal anti-inflammatory drugs (NSAIDs). Possible variants of acute and chronic kidney damage when taking NSAIDs are considered. Acute kidney injury is a serious side effect of NSAIDs associated with suppression of the vasodilatory effects of prostaglandins, decompensation of intrarenal hemodynamics, and an acute decrease in glomerular filtration rate levels. A high risk of acute kidney injury when taking NSAIDs is observed in elderly patients with concomitant diseases and polypharmacy, as well as with an initial impairment of renal function. Taking NSAIDs can cause the development of acute interstitial nephritis in combination with podocytopathy, which is manifested by high proteinuria and nephrotic syndrome in younger patients. The mechanisms and clinical manifestations of analgesic nephropathy - chronic kidney damage leading to progressive renal failure are considered separately. The cause of the development of analgesic nephropathy may be the long-term use of combined analgesic drugs, the so-called analgesic mixtures. The erased clinical picture and the mask of chronic pyelonephritis complicate the diagnosis of this disease. Specific for this pathology is renal papillary calcification on computed tomography in combination with a history of long-term analgesic abuse. Withdrawal of anesthetic drugs can slow down the progression of the disease and the development of end-stage chronic kidney disease. The possibility of the development and progression of chronic kidney disease associated with the certain classes of NSAIDs is discussed. An algorithm for treatment of chronic pain syndrome is presented, depending on the degree of risk of kidney damage.

Зміни деяких біохімічних показників сироватки крові у разі дво- та шеститижневого застосування терапевтичних доз опіоїду та на ранніх термінах відміни препарату

An important issue today is the safety of opioids for the treatment of chronic pain syndrome, which accompanies a number of somatic diseases. Most drugs or their metabolites are excreted through the kidneys and are one of the causes of acute and chronic kidney damage. The aim of the study was to compare some serum biochemical parameters of rats at two and six weeks of therapeutic doses of nalbuphine and to compare them after early withdrawal. This study was performed on 45 white sexually mature male rats weighing 180–260 g. In the serum of experimental animals’ total protein, urea, creatinine, calcium and phosphorus were determined. Statistical calculations were performed using RStudio v. 1.1.442 and R Commander v.2.4-4. Serum total protein in the study groups had small fluctuations in control, but there was a tendency to decrease after 2 weeks of nalbuphine administration and to increase both from the second to the sixth week and with the withdrawal of nalbuphine in the early stages of the experiment. Serum creatinine increased from the second to the sixth week of the experiment both with six weeks of administration (2.23 times higher than control values) and with two weeks of nalbuphine with the subsequent four-week withdrawal (1.63 times higher than control values). Serum urea increased after 2 weeks and 6 weeks of nalbuphine administration, with mean values 6.22 ± 0.47 mmol/l and 7.63 ± 0.74 mmol/l respectively. However, after drug withdrawal the indicator decreased to the control group. Serum calcium in rats decreased after 2 weeks of the experiment to the value (2.16 ± 0.09 mmol/l). After 6 weeks of nalbuphine administration, as after drug withdrawal, serum calcium increased to the level of the control group and was 2.39 ± 0.09 mmol/l and 2.46 ± 0.05 mmol/l respectively. The serum phosphorus index increased after 2 weeks of the experiment and was 2.42 ± 0.05 mmol/l. After 6 weeks of nalbuphine administration and after drug withdrawal, the value decreased to 2.12 ± 0.12 mmol/l and 2.00 ± 0.05 mmol/l respectively. Conclusions. The use of therapeutic doses of nalbuphine for two and six weeks, as well as after drug withdrawal does not affect the concentration of serum total protein of rats. As a result of two- and six-week use of the drug, an impaired renal nitrogen excretion is observed, and hence the structure of the renal corpuscles is altered, which also takes place during four weeks of drug withdrawal after two weeks of use, as evidenced by an increase in urea and creatinine after two weeks of nalbuphine and significant increase in creatinine after drug withdrawal. Two-week administration of nalbuphine leads to hypocalcemia and hyperphosphatemia, indicating impaired renal reabsorption function, while a subsequent four-week administration and withdrawal leads to normalization of these parameters, except for phosphorus, which is reduced.

Facet syndrome. Minimally invasive surgical treatment. Clinical case with a literature review

Background: Degenerative pathology of the facet joints of the lumbar spine remains a significant medical and social problem due to persistent pain syndrome, high incidence and disability rate.
 Clinical case description: A patient complaining of pain and discomfort in the lumbosacral spine on the right, arising in the upright position, intensifying with bending and flexion-extension of the trunk, and periodically spreading to the right gluteal region and along the posterior surface of the thigh, was admitted to the neurosurgical department of the Irkutsk Scientific Center of Surgery and Traumatology. A surgical treatment was performed in the form of dereception of the LIILIII, LIIILIV, LIVLV arch-process joints. In the postoperative period, the patient noted a decrease in the intensity of pain in the lumbosacral spine to 3 points by a visual analog scale and was discharged from the department on the 5th day after the surgery in a satisfactory condition.
 Conclusion: Facet joint pathologies represent a most common nosological form of the degenerative-dystrophic process (spondyloarthrosis) and a potential source of pain with the formation of instability of the spinal motion segment and chronic pain syndrome. The complex anatomical and topographic relationships between the facet joints, intervertebral discs, and radicular nerves force clinicians to pay attention to the pathology of facet syndrome. Understanding the morphological, clinical, and radiological features of the course of the facet joint degeneration makes it possible to increase the diagnostic capabilities for detecting facet syndrome of the lumbar spine and effectively apply transcutaneous surgical technologies for the treatment of chronic pain syndromes.

Pharmacoeconomic analysis of the application of strong opioids for the treatment of chronic pain syndrome in patients with pancreatic cancer

Objective: to evaluate the clinical and economic feasibility of opioid therapy based on the analysis of its cost and effectiveness in patients with chronic pain syndrome in pancreatic cancer.Material and methods. An observational prospective study in parallel groups of patients with chronic pain syndrome associated with pancreatic cancer was carried out. The analysis of cost minimization and cost-effectiveness was applied, as well as pharmacoeconomic modeling, which included the construction of a decision tree in patients receiving morphine sulfate (n=45) and fentanyl TTS (n=45) for pain relief. The sensitivity of the obtained data was assessed using one-way analysis.Results. It was shown that the treatment of chronic pain syndrome in patients with pancreatic cancer with opioid analgesics as part of combined treatment is the least expensive in the morphine sulfate group (incremental cost-effectiveness ratio 144.93). Based on the results of modeling, the prognostic factors of influence on the cost of analgesic therapy were determined: the cost of combined analgesic therapy, the cost of treatment of adverse reactions, and the cost-effectiveness ratio.Conclusion. Analgesic therapy of chronic pain syndrome with morphine sulfate in patients with pancreatic cancer is pharmacoeconomically feasible.

The effects of amultiday (10-14 days) subanesthetic dose IV ketamine infusion in the treatment of refractory chronic pain.

Aim: Ketamine is an anesthetic agent that at lower doses can be a potent analgesic. There has been an interest in the use of low dose ketamine in treatment of chronic pain syndromes. Patients & methods: We report the results of a retrospective observational study for patients diagnosed with a chronic noncancer pain syndrome receiving a 2-week continuous subanesthetic IV ketamine infusion. Results & conclusion: We conclude that a 10-14 days of subanesthetic ketamine infusion in chronic patients results in clinically significant lowering of patients' numerical pain score. Further studies looking at subanesthetic ketamine infusion in a prospective trial of multi-day IV ketamine infusion in chronic refractory chronic neuropathic pain are needed to further assess the efficacy of ketamine.