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.

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.

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.

Tolerability of the capsaicin 8% patch following pretreatment with lidocaine or tramadol in patients with peripheral neuropathic pain: a multicentre, randomized, assessor-blinded study.

BACKGROUND: Application of the capsaicin 8% patch is associated with treatment-related discomfort. Consequently, pretreatment for 60 min with anaesthetic cream is recommended; however, this may be uncomfortable and time consuming. METHODS: We conducted a multicentre, randomized (1:1), assessor-blinded study in patients with peripheral neuropathic pain to assess tolerability of the capsaicin patch following topical lidocaine (4%) or oral tramadol (50 mg) pretreatment. The primary endpoint was the proportion of patients tolerating capsaicin patch application (ability to receive ≥90% of a 60-min application). Numeric Pain Rating Scale (NPRS) scores were assessed before, during and after treatment. RESULTS: Overall, 122 patients were included (61 per arm). The capsaicin patch was tolerated by 121 patients. Tolerability of the capsaicin patch was similar following pretreatment with lidocaine and tramadol. Following patch application, pain levels increased up to 55 min (change from baseline of 1.3 for lidocaine and 1.4 for tramadol). After patch removal, tramadol-treated patients experienced greater pain relief up to the end of day 1; in the evening, mean changes in NPRS scores from baseline were 0 for lidocaine and -1 for tramadol. Proportions of patients reporting increases of ≥2 NPRS points or >33% from baseline at one or more time point(s) on the day of treatment were similar between arms. Adverse event incidence was comparable between arms. CONCLUSIONS: Capsaicin 8% patch tolerability was similar in the two arms, with comparable results for most secondary endpoints. Tramadol given 30 min before patch application should be considered as an alternative pretreatment option in patients receiving capsaicin patch treatment.

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.

Small mammals: paratenic hosts for species of Toxocara in eastern Slovakia.

Toxocara spp., an aetiological agent of a serious helminthozoonosis, is a common roundworm of domestic and wild carnivores worldwide. The study aimed to estimate the seroprevalence of Toxocara in small mammals from different localities in eastern Slovakia. Anti-Toxocara antibodies were detected in 6.4% out of 2140 examined animals trapped in eastern Slovakia. Due to their high density and observed high seroprevalence of toxocariasis, Apodemus agrarius, A. flavicollis, Myodes glareolus and Mus spicilegus (10.9, 4.2, 3.6 and 11.2%, respectively) represent important sources of the infection. A significant correlation between type of food and Toxocara positivity was detected: granivores (7.2%) and invertebratophages (7.1%) were positive more frequently than herbivores (2.1%). In the years monitored, cyclic changes of seroprevalence were observed. A higher prevalence of antibodies in the spring was followed by a decrease in summer. In autumn, seroprevalence started to rise and stayed at a similar level through the winter. Seroprevalence of the examined animals confirms their contact with Toxocara spp. and demonstrates the presence of the aetiological agent in the monitored locality. Areas with a high prevalence of infected animals present constant infectious pressure on definitive hosts, thus also increasing infection risk for humans and paratenic hosts. The study confirmed the contact of small mammals with Toxocara spp. and demonstrated the presence and circulation of an aetiological agent in the localities monitored in eastern Slovakia.

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.

[Leptospira antibodies in small mammals in Eastern Slovakia]. / Výskyt protilátok proti leptospíram u drobných cicavcov na východnom slovensku.

During the five years (1991-1995) mostly free living small mammals were examined serologically for the presence of antibodies to leptospira. Serological examinations were used by Kmety and Bakoss (1978). Altogether, 2493 individuals of 22 species were examined, an important part of host material (69.6%) was caught in two lowland areas which are intensively cultivated landscapes (East Slovakian Lowland and Kosická kotlina basin). The remaining material comes from submontane areas with less agricultural activities. Apodemus flavicollis, A. agrarius, Clethrionomys glareolus were the most frequently examined species. Antibodies to leptospira were demonstrated in 123 mammals (i. e. in 5.0% of hosts) of eleven species. The highest percentage of positive hosts were recorded in 1993 (8.8%) and the lowest (2.6%) in 1995, but the examined samples were different in size and structure of host species. In six most dominant species higher values of antibodies to leptospira were detected in Microtus arvalis (9.2%), followed by Apodemus flavicollis (5.6%), A. agrarius (5.4%) and A. microps (4.9%). The lowest values were found in Clethrionomys glareolus (2.5%) and Sorex araneus (2.3%). In examined hosts we found antibodies to six serovars of leptospira. The most frequently observed antibodies were to leptospira of the serovar L. grippotyphosa (63.2%) and leptospira of the serovar L. sejroe (26.4%). We recorded nonsignificant differences between the values of prevalence to antibodies in small mammal communities from lowland and submontane areas, resp. Our results confirmed differences in the leptospira serovar structure in small mammals of Bohemia and Slovakia, they were connected with different historical development of both areas. Comparing our results with previous examinations (about 20 years ago) in small mammals from eastern Slovakia, a decline of positivity and lower number of leptospira serovars were recorded.