Clinical Neuroscience

[Drug therapy of neuropathic pain in mirror of latest reccommandations]

KISS Gábor

MARCH 25, 2015

Clinical Neuroscience - 2015;68(03-04)

[Neuropathic pain is considered as a special type of different pain conditions. It’s pathophysiological basis and treatment is completely different from the nociceptive pain. The first comprehensive therapeutic guidelines published approximately a decade ago recommended tricyclic antidepressants, anticonvulsants and opioids. The recent summary presents and evaluates national and international guidelines issued in the last five years. The most frequently suggested drugs by all guidelines are amitriptyline, duloxetine, gabapentin and pregabalin. Pregabalin is the only drug that is recommended first line in all guidelines referred. Opioids are in the second or third line. There seems to be no major development in the pharmacological treatment of the neuropathic pain compared to the earlier recommendations. High quality studies of head to head comparisons and effectiveness of combination therapy are still lacking.]



Further articles in this publication

Clinical Neuroscience

[Measuring of functional impairment of lumbal spine]


[Background and purpose - The purpose of our study was to outline the Hungarian validation process of the Oswestry Disability Index, the Quebec Back Pain Disability Scale, the Roland-Morris Disability Questionnaire and the Core Outcome Measurement Index, as well as to draw up recommendations regarding their future applications. Methods - The Hungarian versions were brought to life after a cultural and linguistic adaptation. Next to the above-mentioned questionnaires, the questionnaire booklet used for validation also contained the WHOQoL-BREF general quality of life questionnaire and a pain measuring Visual Analog Scale. The data of low-back pain patients were registered twice in two weeks. We determined the internal homogeneity (Cronbach alpha), reproducibility, standard error of measurement and the minimal detectable change of the questionnaires. Patients were assigned into different two subgroups (surgical / non-surgical, with / without affection of nerve roots) and differences between the subgroups were examined with the help of the questionnaires. We determined the physical subscale of the WHOQoL-BREF and the correlation between the pain and the studied questionnaires. Results - The value of Cronbach alpha was between 0.85 and 0.95. All four questionnaires showed significant differences (p<0.001) between the subgroups. The correlation studies brought strong and significant results (p<0.001, r>0.5) in every case. The values of reproducibility were between 0.93-0.92. The results of standard measurement error: 4.8 (Oswestry), 5.2 (Quebec), 1.6 (Roland-Morris), 0.59 (Core Index). The minimal detectable change was 13; 14; 4, and 2 points, respectively. Conclusion - The Hungarian versions of all four questionnaires are valid. They can be applied with scientific certainty to measure low back pain patients. From the studied questionnaires, we especially recommend the wide-raging application of the Oswestry Disability Index and the Core Outcome Measurement Index based on their psychometric and application features. ]

Clinical Neuroscience

[Teriflunomide: new oral immunmodulant drug in therapy of multiple sclerosis]

BENCSIK Krisztina, RÓZSA Csilla, VÉCSEI László

[Multiple sclerosis (MS) is the autoimmune, demyelinating, neurodegenerative disorder of the central nervous system (CNS). There are nine drugs available in Hungary reimbursed by the National Health Insurance Fund of Hungary (OEP) to reduce the activity of the disease, from which seven can be used as first line therapies. We have approximately 20 years of experience with the interferon b-1a/1b and glatiramer-acetate products. Though in case of approximately 30% of the patients using one of the first line drugs, the disease remains active, that we call break-through disease. The reasons for break-through disease could be the insufficient adherence and compliance, the appearance of neutralizing antibodies or the high activity of the disease. One of the oral immunomodulating drugs for MS, teriflunomide, was registered in Europe in 2013. Because of the anti-proliferative and anti-inflammatory effect of teriflunomide, it can be used for the reduction of the disease activity in the relapsing-remitting course of MS. The effect of teriflunomide was proved in one Phase II. and four Phase III. (TEMSO, TOWER, TENERE, TOPIC) studies. Teriflunomide 14 mg once daily was able to demonstrate in two consecutive placebo-controlled phase 3 clinical trials that significantly reduces the relapse rate (31.5% and 36.3%) and in both studies significantly reduces the sustained disability progression (29.8% and 31.5%) moreover delays the appearance of the clinically definitive MS in patients with clinically isolated syndrome (CIS). According to the TENERE study there were no significant differences observed between teriflunomide 14 mg and IFNb-1a s.c. in time to failure and annualized relapse rate but the treatment satisfaction domains of global satisfaction, side-effects and convenience were significantly improved with teriflunomide compared with s.c. IFNb-1a. ]

Clinical Neuroscience

[Do previous offences predict violent acts in psychiatric patients? A retrospective study in Hungary]

BARAN Brigitta, SZABÓ Ádám Ferenc, KARA Borbála, KOVÁCS Magdolna, UZONYI Adél, ANTAL Albert, UNGVARI S Gabor, GAZDAG Gábor

[Aim - To investigate the presence of offences in the previous past history of perpetrators of violent acts who have undergone forced medical treatment. Methods - The documentation of all patients released over a 10-year period from the National Institute of Forensic Psychiatry (IMEI) was reviewed. A comparison was drawn between patients who were convicted of any type of offense before the violent act (patients with previous offences-PPO) and those who were not (patients with no previous offences-PNO). Results - Eighty-six (29%) and 208 (71%) patients formed the PPO and PNO groups, respectively. Prior contact with psychiatric services was significantly higher in the PPO group (p=0.038) and this group was also more likely to offend under the influence of a psychoactive substance (p<0.001). Exceptional brutality and other qualifying factors were more frequent in the PNO group (p=0.019). Conclusion - As IMEI is the only forensic institution in Hungary, the picture presented here reflects the situation in the entire country. A recidivism rate of 29% is within the internationally published range. ]

Clinical Neuroscience

[Lack of associations between CLU and PICALM gene polymorphisms and Alzheimer’s disease in a Turkish population]

SEN Aysu, ARSLAN Mehtap, ERDAL Emin Mehmet, AY Izci Ozlem, YILMAZ Gorucu Senay, KURT Erhan, ARPACI Baki

[Background and purpose - To investigate the association between the rs11136000 single nucleotide polymorphism (SNP) of the clusterin (CLU) gene, the rs541458 and rs3851179 SNPs of the phosphatidylinositol-binding clathrin assembly protein (PICALM) gene and Alzheimer’s disease (AD) in a Turkish population, and to determine whether there are any relationships between the CLU and the PICALM genotypes and behavioral and psychological symptoms of dementia (BPSD) in the Turkish population. Methods - One-hundred and twelve AD patients and 106 controls were included in this study. BPSD were evaluated by the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD). SNPs in the CLU and the PICALM gene were genotyped by Real-Time PCR. Genotype distributions were assessed for the groups of patients and controls, for the patient groups with and without each BPSD, and “No BPSD” and “BPSD”. Results - The CLU and the PICALM genotypes were similar in the AD and control subjects, and the groups with and without each BPSD. There were also no significant differences between the “No BPSD” and the “BPSD” groups for the PICALM genotypes, but even without a statistical significance, it is notable that none of the “No BPSD” patients had genotype pattern CLU-rs11136000-TT, and the female subjects with genotype pattern CLU-rs11136000-TT had higher mean score of BEHAVE-AD. Conclusion - This study claims that investigated SNPs are not genetic risk factors for AD in a Turkish population. In addition, the rs541458 and rs3851179 of PICALM SNPs are not related to development of BPSD, but the rs11136000 of CLU SNP might be related to development of BPSD in AD female Turkish subpopulation.]

Clinical Neuroscience

[Genetic polymorphisms of human beta-defensins in patients with multiple sclerosis]


[Aims - Recent studies have started to elucidate the contribution of microbiome to the pathogenesis of multiple sclerosis (MS). It is also supposed, that neuropathological alterations might be associated with abnormal expression and regulatory function of antimicrobial peptides (AMPs), including defensins. It is in our interest to investigate the relevance of the single nucleotide polymorphisms (SNPs) of the DEFB1 gene and the copy number polymorphism of the DEFB4 genes in MS. Methods - DEFB1 polymorphisms: c.-20G > A (rs11362), DEFB1 c.-44C > G (rs1800972), DEFB1 c.-52G>A (rs1799946), and the DEFB4 gene copy number were investigated in 250 MS patients The control patients comprised 232 age- and gender-matched healthy blood donors. The occurrence of the human b-defensin 2 peptide (hBD2) in the plasma of controls and patients was determined by ELISA. Results - The DEFB1 c.-44C>G polymorphism the GG protective genotype was much less frequent among patients than among the controls. A higher frequency of a lower (<4) copy number of the DEFB4 gene was observed in the patients with MS as compared with the controls (43% vs. 28%, respectively). The median levels of the circulating hBD2 in the patients were 150.6±12.71 pg/ml vs. 262.1±23.82 pg/ml in the control group (p<0.0001). Our results suggest that b-defensins play role in the development of MS.]

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Related contents

Lege Artis Medicinae

[Neuropathic pain: spotligth on amitriptyline]

FEHÉR Gergely, POHL Marietta, KAPUS Krisztián, GOMBOS Katalin, PUSCH Gabriella, MÁK Kornél, KOLTAI Katalin, BANK Gyula, KÓSA Gábor, VARJASI Gábor, TIBOLD Antal

[The management of neuropathic pain is a challenge both for patients and medical professioners. A novel approach is recommended for its management based on the novel neurobiological results of pain research. Multidisciplinary teams and medical consensus are required due to the variety of symptoms and concomittant psychopathology. This approach allows us to avoid extensive diagnostic and trerapeutic workups and appropiate treatment for our patients. Most extensive evidence is available for pharmacological treatment, and currently recommended first-line treatments include antidepressants (tricyclic agents and serotonin-norepinephrine reuptake inhibitors) and anticonvulsants (gabapentin and pregabalin). The aim of our review was to collect articles focusing on the efficacy of the most widely available and cheapest tricyclic agent, amitriptyline in different neuropathic pain conditions. ]

LAM Extra for General Practicioners

[A holistic approach to neuropathic pain]

KISS Gábor

[Neuropathic pain is a chronic pain disorder due to a primary lesion and/or dysfunction of the peripheral or central nervous system. This tormenting condition causes a lot of distress to the patients, impairs their quality of life, and demands significant expenses. Chronic neuropathic pain is frequently under-diagnosed and mistreated. Explanations for these problems are the complex underlying pathomechanism, variability of symptoms, difficulties in diagnosis, and the differences between the treatment of this and other painful disorders. In addition, comorbid conditions such as anxiety, depression, and sleep disorders are often overlooked. Apart from the diagnostic difficulties, also treatment is usually unsatisfactory. Frequently NSAIDs are used, but they are usually not effective. Undoubtedly, even with the use of evidence-based treatment - such as duloxetine and pregabalin - complete pain relief is not always possible. Lack of proper medical education also contributes to problems in diagnosis and treatment. In western countries, diabetes is the most common cause of polyneuropathy. Painful diabetic neuropathy is the most intensely studied neuropathic pain condition; a lot of evidence comes from randomized controlled trials of this type of neuropathy. The same drugs as in the case of other neuropathic pain conditions are used for the symptomatic treatment of painful diabetic neuropathy. Etiological therapy is based on the best achievable glycemic control. A combination of etiological and symptomatic therapy can be a future treatment, but proving this will require further studies.]

Clinical Neuroscience

Thrombocytopenia with gabapentin usage

ATAKLI Dilek, YUKSEL Burcu, AK Dogan Pelin, SARIAHMETOGLU Hande, SARI Hüseyin

Gabapentin is an antiepileptic drug approved for adjunctive therapy for partial seizures. We report a case of a patient who had thrombocytopenia with the dose of 2400 mg/day of gabapentin. The causal relationship between gabapentin and thrombocytopenia was revealed by dramatic increase in thrombocyte count following the cessation of the gabapentin treatment. To our knowledge, this is the first case report with a hematopoietic side effect of gabapentin.

Clinical Neuroscience

Cerebral vasomotor reactivity in fibromyalgia patients and its relationship to central neuropathic pain

GULER Sibel, KURTOGLU S. Hakan, KEHAYA Sezgin, PAMUK Nuri, CELIK Yahya

Background - Cerebral vasomotor reactivity, defined as the cerebral vasculature response to hypoxia, is not wellunderstood in fibromyalgia (FM) patients. This study investigated the difference in the cerebrovascular reactivity (i.e., responsiveness to hypercapnia was evaluated by use of breath- holding index) to the breath-holding index (BHI) between patients with fibromyalgia and a group of normal controls. Methods - The study included 40 FM patients and 40 healthy subjects. Cerebrovascular reactivity was evaluated using the BHI, which is a nonaggressive, well-tolerated, real-time, reproducible screening method to study cerebral haemodynamics. Insonation depth and basal velocity were symmetrical and not significantly different between the two groups (p>0.05). All patients completed the Revised Fibromyalgia Impact Questionnaire (FIQR), Hospital Anxiety and Depression Scale (HADS), visual analogue scale (VAS), and the somatization subscale of the SCL-90-R symptom checklist. Results - The BHI ranged from 0.30 to 2.20 (mean 1.11±0.45) in the FM patients and 1.10 to 2.80 (mean 1.90±0.35) in the control group (p<0.001). Disease duration and right BHIaverage and left BHIaverage values exhibited a significant negative correlation (r=-0.877; p<0.001, r=-0.842; p<0.001, respectively). As pain and fatigue scores increased, the right BHIaverage and left BHIaverage values decreased (r=-0.431; p=0.005, r=-0.544; p<0.001, r=-0.341; p=0.031, r=-0.644; p<0.001, respectively). Conclusions - BHI values showed that cerebrovascular reactivity in FM patients decreased in comparison to healthy individuals. BHI decreased as disease duration and severity increased. Cerebrovascular reactivity decreased in FM patients, and this phenomenon should be accepted as an abnormality. Additionally, this outcome may have been the result of a mechanism responsible for central neuropathic pain.

LAM Extra for General Practicioners


NAGY Katalin

[Pain is the most common symptom in rheumatology, which can be of mechanical or inflammatory origin, acute and chronic, nociceptive, neuropathic and psychogenic. Pain can be relieved by analgesics, nonsteroidal anti-inflammatory drugs, opioids, adjuvants and special drugs depending on the etiology, for example a gout attack can be stopped by colchicine. For pain relief, we use therapeutic guidelines of the World Health Organization (WHO), which recommends the use of analgesics, NSAIDs and adjuvants as the first step, weaker opioids as the second, and strong opioids as the third step. In rheumatology, the first step's drugs are generally used. If possible, NSAIDs should be administered briefly, potentially combined with analgesics and muscle relaxants. If pain management is insufficient, tramadol should be given. Pain relief in rheumatology also include the use of local and intraarticular injections, physiotherapy, TENS and balneotherapy. Complex therapies that combine the above mentioned methods is often more effective than the use of medications only.]