The opioid systems and the role of glial cells in the effects of opioids

Understanding of the molecular mechanisms in the opioid systems in chronic pain should produce new, more effective methods of the pharmacotherapy of pain. Pharmacological suppression of glial activation in combination with morphine, methadone, fentanyl and buprenorphine may be an important aspect of pain therapy. Long-term use of the classical opioid analgesics in patients with chronic pain processes results in tolerance, and the search of new treatment strategies based on the recognised mechanisms of pain is an important clinical and scientific issue.Understanding of the molecular mechanisms in the opioid systems in chronic pain should produce new, more effective methods of the pharmacotherapy of pain. Pharmacological suppression of glial activation in combination with morphine, methadone, fentanyl and buprenorphine may be an important aspect of pain therapy. Long-term use of the classical opioid analgesics in patients with chronic pain processes results in tolerance, and the search of new treatment strategies based on the recognised mechanisms of pain is an important clinical and scientific issue

Systemy opioidowe oraz udział komórek glejowych w efektach opioidów

Zrozumienie molekularnych mechanizmów zachodzących w systemach opioidowych w bólu przewlekłym powinno wyznaczyć nowe skuteczniejsze metody farmakoterapii bólu. Farmakologiczne zahamowanie aktywacji gleju w połączeniu z morfiną, metadonem, fentanylem i buprenorfiną może stanowić ważny aspekt terapii bólu. Długotrwałe stosowanie klasycznych opioidowych leków przeciwbólowych u pacjentów z przewlekłymi procesami bólowymi wywołuje tolerancję, a poszukiwanie nowych strategii leczenia na bazie poznanych mechanizmów bólu stanowi istotny problem zarówno kliniczny, jak i naukowy

Blockade of CCR4 diminishes hypersensitivity and enhances opioid analgesia : evidence from a mouse model of diabetic neuropathy

Chemokine signaling has been implicated in the pathogenesis of diabetic neuropathy; however, the role of chemokine CC motif receptor 4 (CCR4) remains unknown. The goal was to examine the function of CCR4 in hypersensitivity development and opioid effectiveness in diabetic neuropathy. Streptozotocin (STZ; 200 mg/kg, intraperitoneally administered)-induced mouse model of diabetic neuropathy were used. An analysis of the mRNA/protein expression of CCR4 and its ligands was performed by qRT-PCR, microarray and/or Western blot methods. C021 (CCR4 antagonist), morphine and buprenorphine were injected intrathecally or intraperitoneally, and pain-related behavior was evaluated by the von Frey, cold plate and rotarod tests. We observed that on day 7 after STZ administration, the blood glucose level was increased, and as a consequence, hypersensitivity to tactile and thermal stimuli developed. In addition, we observed an increase in the mRNA level of CCL2 but not CCL17/CCL22. The microarray technique showed that the CCL2 protein level was also upregulated. In naive mice, the pronociceptive effect of intrathecally injected CCL2 was blocked by C021, suggesting that this chemokine acts through CCR4. Importantly, our results provide the first evidence that in a mouse model of diabetic neuropathy, single intrathecal and intraperitoneal injections of C021 diminished neuropathic pain-related behavior in a dose-dependent manner and improved motor functions. Moreover, both single intrathecal and intraperitoneal injections of C021 enhanced morphine and buprenorphine effectiveness. These results reveal that pharmacological modulation of CCR4 may be a good potential therapeutic target for the treatment of diabetic neuropathy and may enhance the effectiveness of opioids

Spontaneous cerebrospinal fluid leak at the clivus

We present a case report of a 60-year-old woman with a spontaneous cerebrospinal fluid leak at the clivus, obesity and no history of trauma. Follow-up imaging scans confirmed enlargement of the defect within the posterior clival framework to the size of 16 × 9 × 4 mm with a suspected meningocerebral hernia. The surgeons used the “two nostrils – four hands” endoscopic operating technique. The patient reported a history of cerebrospinal fluid leaks lasting for 3 years, with increasingly shorter leak-free periods and an increasing incidence of inflammatory complications. The patient recovered without complications, and she was discharged 14 days after the surgery. Good local outcome and improved patient condition were achieved postoperatively

Classification supporting COVID-19 diagnostics based on patient survey data

Distinguishing COVID-19 from other flu-like illnesses can be difficult due to ambiguous symptoms and still an initial experience of doctors. Whereas, it is crucial to filter out those sick patients who do not need to be tested for SARS-CoV-2 infection, especially in the event of the overwhelming increase in disease. As a part of the presented research, logistic regression and XGBoost classifiers, that allow for effective screening of patients for COVID-19, were generated. Each of the methods was tuned to achieve an assumed acceptable threshold of negative predictive values during classification. Additionally, an explanation of the obtained classification models was presented. The explanation enables the users to understand what was the basis of the decision made by the model. The obtained classification models provided the basis for the DECODE service (decode.polsl.pl), which can serve as support in screening patients with COVID-19 disease. Moreover, the data set constituting the basis for the analyses performed is made available to the research community. This data set consisting of more than 3,000 examples is based on questionnaires collected at a hospital in Poland.Comment: 39 pages, 5 figure

IgG4-related inflammatory orbital pseudotumors : a retrospective case series

Orbital diseases may be divided into congenital defects of the orbit, infectious and inflammatory diseases, orbital tumors (including malignant and benign tumors) and injuries. Idiopathic inflammatory syndromes are often encountered within the orbit and are usually classified as orbital pseudotumors. The etiology of pseudotumors of the vision organ is unknown. Infectious agents, autoimmune disorders and improper healing are taken into consideration in the pathogenesis of this disorder. Thanks to detailed studies conducted in recent years, a new disease syndrome was identified in 2001. It is known as IgG4-related disease, and its differentiation is based on the analysis of IgG4 levels in the affected tissues. Orbital locations of the disease were first reported in Japan as late as at the end of 2009. This finding triggered the European studies on this subject. To date, no such studies have been conducted in Poland. The starting study population consisted of 167 patients with isolated infiltrative tumor diseases within the orbital region treated at the Department of Otolaryngology, Head and Neck Surgery of the Medical College Jagiellonian University in Krakow. Detailed analysis and diagnostic screening for IgG4-related disease was performed in a total of 17 patients diagnosed with orbital pseudotumor

Non-invasive transcutaneous Supraorbital Neurostimulation (tSNS) using Cefaly® device in prevention of primary headaches

Headaches are one of the most common pain syndromes experienced by adult patients. International Classification of Headache Disorders identifies about 300 different entities. Primary headaches (migraine, tension-type headache, trigeminal autonomic cephalalgias, other primary headaches) has the common occurrence. Although effective treatment of these disorders is possible, it is inefficient or poorly tolerated in some patients. Neuromodulation methods, being element of multimodal treatment, provide an additional treatment option in pharmacotherapy-refractory patients. Both invasive and non-invasive stimulation methods are used. The non-invasive techniques is transcutaneous nerve stimulation using Cefaly® device. In this study, Cefaly® was used as prevention treatment in patients with pharmacotherapy-refractory headaches. This device is indicated for the prophylactic treatment of episodic primary headaches. A total of 91-patients (30 without and 61 with tSNS) were enrolled in the study, including 60-patients with migraine and 31-patients with other primary headaches. Ten courses of non-invasive peripheral (supraorbitral/supratrochlear) nerves stimulation were delivered to 57-patients; in the remaining 4 patients, the treatment was abandoned due to poor tolerance. Patients were observed for 30 days after stimulation treatment. Compared to the pre-treatment period, the reduction in the intensity of pain was observed in both the migraine group and patients with other types of headaches; this included the number of pain episodes being reduced by half, with simultaneous reduction in average pain intensity and duration of individual pain episodes. The subjective assessment of pain reduction was in the range of 40–47%. Based on our data we recommend tSNS as useful tool in the prophylaxis of primary headaches, including migraine