Neuromodulation in the treatment of postoperative epidural fibrosis: comparison of the extent of epidural fibrosis and the effect of stimulation.

The goal was to prove that when a cohort of patients is chosen precisely, dorsal column stimulation provides significant improvement to quality of life. We studied a cohort of 50 patients with the history of failed back surgery syndrome coupled with epidural fibrosis (EF). A percutaneous implantation technique was used in each of the 50 patients. The study group was composed of 20 women and 28 men aged 26-67 years (mean age 49). A prospective observational questionnaire-based study was used. According to the methods, Ross's classification was adjusted to four degrees of scar size for our study objective. Despite this adjustment, it was not possible to statistically evaluate our research, due to very similar results in Groups I, III and IV. Patients without epidural fibrosis were assigned to Group 0, and patients with EF of different ranges were assigned to Group 1. The mean change in visual analogue scale DeltaVAS after our division into Group 0 was 4.82; for Group 1 it was 6.13. Evaluation of EF and DeltaVAS correlation by paired t-test shows a statistically higher effect of spinal cord stimulation (SCS) in the epidural fibrosis group, compared to group 0 without postoperative epidural fibrosis (p=0.008). The extent of epidural fibrosis is an important factor for Failed back surgery syndrome (FBSS). FBSS is the basis for the existence of neuropathic pain after lumbar spinal surgery. There is clear evidence of a correlation between patients with epidural scar formation on MR scan and the effect of dorsal column stimulation.

Effect of tapentadol on experimental model of orofacial pain - a pilot study.

Acute orofacial pain is associated with significant disability and has a detrimental impact on quality of life. Although various origins of the pain in trigeminal territory can be identified an odontogenic pathology is the most common cause of acute orofacial pain in patients. Due to complex pathophysiology drugs with multitarget action might provide beneficial effect in pain management. The aim of the present study was to experimentally examine the anti-nociceptive effects of tapentadol, an opioid agonist and a norepinephrine reuptake inhibitor (MOR/NRI), in our animal model of orofacial pain. We tested the effect of tapentadol at gradual doses of 1, 2 and 5 mg/kg during thermal and mechanical stimulation in the trigeminal area of adult rats. We observed that tapentadol exhibits antinociceptive effect at dosages of 2 mg/kg and 5 mg/kg and only in association with mechanical stimulation.

Prognostic Value of MicroRNAs in Patients after Myocardial Infarction: A Substudy of PRAGUE-18.

BACKGROUND: The evaluation of the long-term risk of major adverse cardiovascular events and cardiac death in patients after acute myocardial infarction (AMI) is an established clinical process. Laboratory markers may significantly help with the risk stratification of these patients. Our objective was to find the relation of selected microRNAs to the standard markers of AMI and determine if these microRNAs can be used to identify patients at increased risk. METHODS: Selected microRNAs (miR-1, miR-133a, and miR-499) were measured in a cohort of 122 patients from the PRAGUE-18 study (ticagrelor vs. prasugrel in AMI treated with primary percutaneous coronary intervention (pPCI)). The cohort was split into two subgroups: 116 patients who did not die (survivors) and 6 patients who died (nonsurvivors) during the 365-day period after AMI. Plasma levels of selected circulating miRNAs were then assessed in combination with high-sensitivity cardiac troponin T (hsTnT) and N-terminal probrain natriuretic peptide (NT-proBNP). RESULTS: miR-1, miR-133a, and miR-499 correlated positively with NT-proBNP and hsTnT 24 hours after admission and negatively with left ventricular ejection fraction (LVEF). Both miR-1 and miR-133a positively correlated with hsTnT at admission. Median relative levels of all selected miRNAs were higher in the subgroup of nonsurvivors (N = 6) in comparison with survivors (N = 116), but the difference did not reach statistical significance. All patients in the nonsurvivor subgroup had miR-499 and NT-proBNP levels above the cut-off values (891.5 ng/L for NT-proBNP and 0.088 for miR-499), whereas in the survivor subgroup, only 28.4% of patients were above the cut-off values (p = 0.001). CONCLUSIONS: Statistically significant correlation was found between miR-1, miR-133a, and miR-499 and hsTnT, NT-proBNP, and LVEF. In addition, this analysis suggests that plasma levels of circulating miR-499 could contribute to the identification of patients at increased risk of death during the first year after AMI, especially when combined with NT-proBNP levels.

Electrode movement prevention - an animal model.

Electrode migration is the most common complication of spinal cord stimulation (SCS). The problem of longitudinal migration has already been solved, but lateral migration remains the most common current complication. The present article describes new electrodes fixation opportunities for the reduction of lateral migration in SCS. The pig was chosen as an animal model to illustrate a new protocol of electrode fixation for the control of lateral and longitudinal migration. The displacement of the electrode was measured using two different optical methods: the digital image stereo-correlation and the digital image processing methods. Fixation with two anchors has always considerably reduced electrode displacement and when fixation is done with two anchors and a loop then lateral migration is reduced by 62.5 % and longitudinal migration is reduced by 94.1 %. It was shown that the results are significantly different at the alpha=0.001 significance level. Based on a statistical evaluation it is possible to state that the differences between experimental results obtained for three different protocols of lead fixation are statistically significant and we can recommend the new fixation method for common practice.

The treatment of orofacial pain by using transcranial direct current stimulation.

Neurostimulation methods are used in the treatment of chronic pain, although mainly for pharmacology resistant pain. Transcranial Direct Current Stimulation (tDCS) is a non-invasive neurostimulation method using low direct current (0.029-0.08 mA/cm2) applied to a cathode and anode, which directly stimulates the cranial surface. The applied current causes the most significant changes directly under the electrodes: the cathode reduces the excitability of cortical neurons, whereas the anode increases excitability. The effect of stimulation usually lasts a few hours up to a few days. We observed 19 patients with chronic orofacial pain. Inclusion criteria for the study were the following: orofacial pain, stable analgesic medication for at least one week before the beginning of stimulation and during its course, and age 18-75 years old. Patients with severe organic brain damage or seizure disease (epilepsy) were not included. The most common diagnosis was secondary trigeminal neuralgia after dental surgery. We measured thermal and tactile stimulation on the face before and after tDCS, then at 14 days. The total follow-up period lasted six months. We evaluated pain on a numerical scale (0-10) at each follow-up. We used sets of inventories focused on the examination of pain (a short form of McGill inventory), depression, anxiety, and pain interference with daily activities. tDCS is a non-invasive stimulation technique that is affordable and can be easily administered, especially when compared to other neurostimulation techniques. Only 15 patients out of the total number of 19 responded to the questionnaires.

The glycation products before and after therapy for acute and chronic pain.

Pain increased the number of free radicals in the body. Previously, we studied changes mainly in oxygen and nitroxide free radicals and described these changes relative to the lipids and saccharides. In this article we focus on changes relative to proteins. Assessment of AGE products (advanced glycation end-products) was carried out by measuring fluorescence. Patients were divided into two groups: 15 patients with acute pain and 17 patients with chronic pain. Acute pain was associated with a variety of surgical procedures and patients were examined before and after surgical procedures. The group of patients with chronic pain suffered from various types of chronic pain, but mainly back pain. In patients with acute pain, total protein (TP) decreased after surgery, as did the level of AGE and the AGE/TP ratio. Nonetheless, post-operative pain increased. In patients with chronic pain, neither total protein, AGE, or AGE/TP changed, despite significant pain relief being reported after treatment. Changes in proteins, as biochemical markers, before and after pain treatment did not show any significant changes. In patients with acute pain, the recorded changes only lasted for 3-5 days after the operation. While in chronic pain, there were no significant changes at all. The assumption that changes in proteins, as biomarkers, would have the same importance as changes in lipids and saccharides was not proven.

Theta burst stimulation in the treatment of chronic orofacial pain: a randomized controlled trial.

Theta burst stimulation (TBS) is a modified form of high-frequency repetitive transcranial magnetic stimulation (rTMS) with promising effect in chronic pain. The aim of our double-blind, sham-controlled, parallel-group, randomized study was to assess an efficacy of intermittent TBS (iTBS) in the treatment of patients with chronic orofacial pain. Nineteen patients (twelve females) with chronic orofacial pain were prospectively included and randomly assigned to single session of an active (iTBS) or sham (intermediate TBS; imTBS) stimulation delivered to the primary motor cortex (M1) contralateral to painful side. The primary outcome was pain relief assessed using a visual analogue scale (VAS) after stimulation and at the end of two-week follow- up. The secondary outcomes were changes in the quantitative sensory testing (QST). QST set the threshold for thermal and tactile (touch) sensation in the affected facial area. Intermittent TBS, compared with the sham, showed significant improvement in VAS after stimulation, but not at the end of two-week follow-up. Regarding the secondary outcomes (QST), we failed to find any significant difference between iTBS and sham. Our findings demonstrate that iTBS of M1 transiently provides transient and modest subjective pain relief in chronic orofacial pain.

Do multiple body modifications alter pain threshold?

In recent years, epidemiological data has shown an increasing number of young people who deliberately self-injure. There have also been parallel increases in the number of people with tattoos and those who voluntarily undergo painful procedures associated with piercing, scarification, and tattooing. People with self-injury behaviors often say that they do not feel the pain. However, there is no information regarding pain perception in those that visit tattoo parlors and piercing studios compared to those who don't. The aim of this study was to compare nociceptive sensitivity in four groups of subjects (n=105, mean age 26 years, 48 women and 57 men) with different motivations to experience pain (i.e., with and without multiple body modifications) in two different situations; (1) in controlled, emotionally neutral conditions, and (2) at a "Hell Party" (HP), an event organized by a piercing and tattoo parlor, with a main event featuring a public demonstration of painful techniques (burn scars, hanging on hooks, etc.). Pain thresholds of the fingers of the hand were measured using a thermal stimulator and mechanical algometer. In HP participants, information about alcohol intake, self-harming behavior, and psychiatric history were used in the analysis as intervening variables. Individuals with body modifications as well as without body modifications had higher thermal pain thresholds at Hell Party, compared to thresholds measured at control neutral conditions. No such differences were found relative to mechanical pain thresholds. Increased pain threshold in all HP participants, irrespectively of body modification, cannot be simply explained by a decrease in the sensory component of pain; instead, we found that the environment significantly influenced the cognitive and affective component of pain.

The effect of combined treatment of opioids with methylphenidate on nociception in rats and pain in human.

Methylphenidate hydrochloride (MPH/Ritalin) is a stimulant used for off-label management of cancer-related fatigue and sedation; however, its use in pain treatment is still relatively rare. This study 1) compares the antinociceptive effect of MPH and its combination with morphine (MOR) in adult male Wistar rats after a single administration of MPH, MOR or their combination, and 2) compares the analgesic effects of opioids and Ritalin combined therapy with opioid monotherapy in patients with cancer pain. To objectively assess physical activity during a three-week monitoring period, patients were equipped with Actiwatch Score Actigraph. Patients performed daily evaluations of pain intensity and frequency, and the extent to which pain interfered with their daily life. Our research with rats supports the evidence that MPH in lower doses has the ability to enhance the analgesic properties of morphine when the two drugs are used in combination. Results from the patient arm of our study found that short-term treatment had no significant effect on intensity or frequency of pain, however it decreased the overall burden of pain; the combined treatment of opioid and Ritalin also showed anti-sedation effects and resulted in mild improvement in one of our patient's quality of life.

Direct measurement of free radical levels in the brain after cortical ischemia induced by photothrombosis.

Tissue ischemia is connected with the production of free radicals (FR). This study was designed to directly measure of the amount of FR in rat brains related to a photothrombotic ischemic event shortly after establishing the lesion. A model of left hemisphere photothrombosis ischemia was used in the experiment. Brains of animals from the experimental group were removed and placed in liquid N(2) for 60 min after the green laser exposure, the control group brains, exposed to the photosensitive dye Rose Bengal (RB), were placed in liquid N(2) for 80 min after RB application, naive control brains were also briefly stored in liquid N(2). Spectroscopy of electron paramagnetic (spin) resonance was used to directly measure FR (hydroxyl (OH(.)) and nitroxyl (NO(.)). Compared to naive controls, both the ischemia and RB groups had significantly higher levels of OH(.), however, there were no differences between them. Comparison of hemispheres, i.e., with and without ischemia, in the experimental group did not show any significant difference in OH(.). NO(.) were elevated in the ischemia and RB groups compare to naive controls. Higher levels of NO(.) were found in hemispheres with ischemia compared to unexposed hemispheres. Increases in OH(.) were probably associated with the action of RB itself in this model of ischemia. Increases in NO(.) were closely related to the pathogenesis of photothrombotic ischemia and could be related to the activity of nitric oxide synthases.

[Chronic fatifue syndrome.] / Chronický Únavový syndrome.

Chronic fatigue syndrome - CFS is a disease that lasts about 6 months in adults and in children three months. Other names are myalgia encephalomyelitis, postviral immune syndrome, chronic fatigue immune dysfunction syndrome. The reasons are biological, genetical, infectious or psychological. The paper discusses the history of chronic fatigue syndrome, epidemiology and its prevalence, clinical course, pathophysiology, diagnosis, therapy and prognosis, and also economics.

Repetitive transcranial magnetic stimulation in the treatment of chronic orofacial pain.

Repetitive transcranial magnetic stimulation (rTMS) is non-invasive neuromodulation method. We applied rTMS for the treatment of farmacoresistant chronic orofacial pain. We compared the effect of 10 Hz and 20 Hz stimulation. The study included 23 patients for 20 Hz stimulation and 36 patients for 10 Hz stimulation with pharmacotherapy resistant chronic facial pain aged 33-65 years with pain duration of at least 6 months. Monitoring of treatment effects was performed within 15 minutes of each rTMS application (days 1-5) and finally stimulation (active vs. sham coil). If compared with data with 10 Hz rTMS study (n=36) and with 20 Hz rTMS (n=23) trials using a parallel design. Only the results obtained in a series of five rTMS treatments in the first step (active n=24, sham n=12), that 20 Hz frequency rTMS using a higher intensity (95 % of motor threshold) to be equally effective relative to VAS (Visual analogue scale) and QST (quantitative sensory testing). In conclusions, the better results with the relief of orofacial pain were obtained with 20 Hz stimulation if compared with 10 Hz stimulation. It was proved with subjective (VAS) and objective evaluation (QST). rTMS can be used in the treatment of chronic intractable pain.

Oxidative stress induced by epileptic seizure and its attenuation by melatonin.

An epileptic seizure and postictal period in addition to well-known features are also characterized by massive consumption of energy. This is thought to lead to oxidative stress and increased generation of free radicals, which is reflected by increased levels of oxidative products. Our previous work described the neuroprotective effects of melatonin in preventing cognitive worsening after a single epileptic seizure. This work was aimed on direct measurement of free radicals in brain tissue using the EPR method 1, 15 and 60 minutes after seizure. The measurement was performed in adult male Wistar rats at the mentioned intervals after a single tonic-clonic seizure induced by flurothyl. In comparison to control animals there was a significant increase in hydroxyl and nitroxyl radicals 60 minutes after the seizure. The levels of hydroxyl radicals were significantly lower in animals that received melatonin 60 minutes before seizure induction compared to animals without preventive treatment. Therefore, melatonin affected the generation of the measured free radicals differently. An important finding was the delayed increase in free radicals after a single seizure in the later phases of recovery.

Gender differences in the effect of prenatal methamphetamine exposure and challenge dose of other drugs on behavior of adult rats.

The aim of the present study was to compare the response to acute application of several drugs in adult male and female rats prenatally exposed to methamphetamine (MA). Spontaneous locomotor activity and exploratory behavior of adult male and female rats prenatally exposed to MA (5 mg/kg) or saline were tested in a Laboras apparatus (Metris B.V., Netherlands) for 1 h. Challenge dose of the examined drug [amphetamine - 5 mg/kg; cocaine - 5 mg/kg; MDMA (3,4-methylenedioxymethamphetamine) - 5 mg/kg; morphine - 5 mg/kg; THC (delta9-tetrahydrocannabinol) - 2 mg/kg] or saline was injected prior to testing. Our data demonstrate that prenatal MA exposure did not affect behavior in male rats with cocaine or morphine treatment, but increased locomotion and exploration in females. Application of amphetamine and MDMA in adulthood increased activity in both sexes, while cocaine and THC only in female rats. Morphine, on the other hand, decreased the activity in the Laboras test in both sexes. As far as sex and estrous cycle is concerned, the present study shows that males were generally less active than females and also females in proestrus-estrus phase of the estrous cycle were more active than females in diestrus. In conclusion, the present study shows that the prenatal MA exposure does not induce general sensitization but affects the sensitivity to drugs dependently to mechanism of drug action and with respect to gonadal hormones.

The effect of vitamin E on plasmatic malondialdehyde levels during surgical removal of ovarian and endometrial carcinomas.

This study deals with the monitoring of plasmatic levels of malondialdehyde, as the main indicator of oxidative damage to biomembranes. Malondialdehyde is determined by high-performance liquid chromatography (HPLC) after derivatization employing 2,4-dinitrophenylhydrazine. A clinical study involving 20 female patients suffering from ovarian and endometrial carcinomas has demonstrated elevated levels of malondialdehyde (10.1 +/- 1.1 microM), compared with the control group (7.5 +/- 2.7 microM). It has been further verified that surgical removal of the tumor leads to an additional increase in the plasmatic malondialdehyde content. This unfavourable situation can be effectively eliminated by administration of a single dose of vitamin E prior to surgery.

Routine pretreatment with abciximab versus standard periprocedural therapy in mechanically ventilated cardiogenic shock patients undergoing primary percutaneous coronary intervention: Subanalysis of the PRAGUE-7 study.

BACKGROUND: The clinical outcome of patients with myocardial infarction (MI) complicated by cardiogenic shock (CS) who require mechanical ventilation (MV) is poor. OBJECTIVE: To analyze the impact of abciximab pretreatment in this high-risk population of MI patients. METHODS: The present study was a retrospective subanalysis of the multicentre randomized Routine Upfront Abciximab Versus Standard Peri-Procedural Therapy in Patients Undergoing Percutaneous Coronary Intervention for Cardiogenic Shock (PRAGUE-7) study, which included 80 MI patients in CS undergoing primary percutaneous coronary intervention (PCI). Patients were randomly assigned into group A (routine pretreatment with an abciximab bolus followed by a 1 h abciximab infusion) and group B (standard therapy). The subanalysis included 37 patients requiring MV. Seventeen patients were in group A and 20 were in group B. The primary end point (death/stroke/reinfarction/new severe renal failure) at 30 days, procedural success (thrombosis in myocardial infarction [TIMI] flow) and frequency of bleeding were assessed. The χ(2) and Student's t tests were used for statistical analysis; P<0.05 was considered to be statistically significant. RESULTS: The primary end point occurred in nine (53%) patients in group A and 12 (60%) patients in group B (P=0.66). TIMI flow after primary PCI was higher in group A (2.75 versus 2.31; P<0.05). Major bleeding occurred in 12% of patients in group A versus 10% of patients in group B (P=0.86). Minor or minimal bleeding was more common in group A (29%) compared with group B (5%; P<0.05). CONCLUSION: The results of the present study suggest that routine pretreatment with abciximab before primary PCI in mechanically ventilated patients with MI complicated by cardiogenic shock was associated with better angiographic results but also with a higher incidence of bleeding.

Do prenatally methamphetamine-exposed adult male rats display general predisposition to drug abuse in the conditioned place preference test?

Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test.

Neurostimulation methods in the treatment of chronic pain.

The main neuromodulatory methods using neurostimulation principles are described. It concerns peripheral nerve stimulation (PNS), spinal cord stimulation (SCS), deep brain stimulation (DBS), motor cortex stimulation (MSC), and repetitive transcranial magnetic stimulation (rTMS). For each method the history, pathophysiology, the principles for use and the associated diagnoses are mentioned. Special attention is focused on the most common neuromodulatory invasive methods like SCS and MCS and non-invasive methods such as rTMS. In addition to the positive effects, side effects and complications are described and discussed in detail. In conclusion, neuromodulatory (neurostimulatory) techniques are highly recommended for the treatment of different types of pharmacoresistant pain.

Ontogeny of the pain.

The article gives an overview of developmental aspects of the ontogeny of pain both in experimental models and in children. The whole article is devoted to the ontogenesis in pain perception and the possible influence on it. The role of endogenous opioids on the development of pain and other important substances such as serotonin, nerve growth factor (NGF) and nicotine are mentioned. There are also important differences of the ontogenesis of thermal and mechanical nociceptive stimulation. The physiological and pathophysiological findings are the backgrounds for principles of treatment, taking into account the special status of analgesics during ontogeny. In particular there are mentioned the special effects of endogenous opioids and especially morphine. It describes the role of vitamin D and erythropoietin during the development of pain perception. This article also mentioned the critical developmental periods in relation to the perception of pain. The attention is paid to stress and immunological changes during the ontogeny of pain. Another important role is played by microglia. The work is concluded by some statements about the use of physiological and pathophysiological findings during the treatment of pain in pediatric practice. Codein analgesia is also described because codein starts to be very modern drug with the dependence.