Can the `yin and yang` BDNF hypothesis be used to predict the effects of rTMS treatment in neuropsychiatry?

Repetitive transcranial magnetic stimulation (rTMS) is a novel technique of non-invasive brain stimulation which has been used to treat several neuropsychiatric disorders such as major depressive disorder, chronic pain and epilepsy. Recent studies have shown that the therapeutic effects of rTMS are associated with plastic changes in local and distant neural networks. In fact, it has been suggested that rTMS induces long-term potentiation (LTP) and long-term depression (LTD) - like effects. Besides the initial positive clinical results; the effects of rTMS are stilt mixed. Therefore new toots to assess the effects of plasticity non-invasively might be useful to predict its therapeutic effects and design novel therapeutic approaches using rTMS. In this paper we propose that brain-derived neurotrophic factor (BDNF) might be such a tool. Brain-derived neurotrophic factor is a neurotrophin that plays a key role in neuronal survival and synaptic strength, which has also been studied in several neuropsychiatric disorders. There is robust evidence associating BDNF with the LTP/LTD processes, and indeed it has been proposed that BNDF might index an increase or decrease of brain activity - the `yin and yang` BDNF hypothesis. In this article, we review the initial studies combining measurements of BDNF in rTMS clinical trials and discuss the results and potential usefulness of this instrument in the field of rTMS. (C) 2008 Elsevier Ltd. All rights reserved.

Into the Island: A new technique of non-invasive cortical stimulation of the insula

Study aim. - We describe a new neuronavigation-guided technique to target the posterior-superior insula (PSI) using a cooled-double-cone coil for deep cortical stimulation. Introduction. - Despite the analgesic effects brought about by repetitive transcranial magnetic stimulation (TMS) to the primary motor and prefrontal cortices, a significant proportion of patients remain symptomatic. This encouraged the search for new targets that may provide stronger pain relief. There is growing evidence that the posterior insula is implicated in the integration of painful stimuli in different pain syndromes and in homeostatic thermal integration. Methods. - The primary motor cortex representation of the lower leg was used to calculate the motor threshold and thus, estimate the intensity of PSI stimulation. Results. - Seven healthy volunteers were stimulated at 10 Hz to the right PSI and showed subjective changes in cold perception. The technique was safe and well tolerated. Conclusions. - The right posterior-superior insula is worth being considered in future studies as a possible target for rTMS stimulation in chronic pain patients. (c) 2012 Elsevier Masson SAS. All rights reserved.

Sleep disorders in climacteric women

Introduction: This paper examines the various factors that contribute to the occurrence of sleep alterations during peri and post climacteric and thus produce significant imperil to women's quality of life. Among the probable causes of insomnia or sleep disorders associated to climacteric stand out the occurrence of vasomotor symptoms, depressive state and respiratory distress during sleep, such as sleep apnea, along with chronic pain, although psychosocial factors related to the climacteric bear major influence on such clinical status. Method: The bibliographic analysis was carried out using several electronic data base namely: Cochrane, Medline, Embase, Bni Plus, Biological Abstracts, Psycinfo, Web Of Science, Sigle, Dissertation Abstracts and ZETOC published in English, Spanish and Poruguese. The key terms used were: sleep, REM sleep, slow wave sleep polysomnography; electroencephalogram; sleep disturbances; disturbances of sleep onset and maintenance; excessive somnolence disturbances; climacteric; menopause; depression; neurobiology; biologic models; circadian rhythm; mental health and epidemiology. Case studies and letters to the editor were excluded. The summaries of the identified studies found in the data base were analyzed and assessed, and the data analyzed separately according to the subjective or objective criteria for data collection. Results: The climacteric transition constitutes a period of major risk for the development of depressive, vasomotor and insomnia symptoms although not caused solely by hypoestrogenism. The diagnostic methods used in the study of sleep disorders range from subjective assessment by means of response to specific questionnaires to the objective analysis of actigraphic or polissonographic daytime and nocturnal reports. Polissonographic studies of the whole night, performed at the laboratory, are the golden method of choice for diagnostic of sleep disorders. Studies point to the high prevalence of sleep disorders in the climacteric, especially insomnia, apnea and periodic movement of legs and also to the fact that this phase of life presents decrease in the quality of sleep. Women in peri and post climacteric show higher sleep latency and difficulty in its maintenance and refer being less satisfied with its quality even when compared to those who are not climacteric. Exception made to the vasomotor symptomatology, the other climacteric complaints such as mood disturbances, libido alterations, cognitive deficit, articular pain and sleep disorders are markedly associated to psychosocial factors, lifestyle and especially to women's perception of what the climacteric means to their lives. Conclusion: The analysis of the available studies revealed a proneness to deterioration of quality of life of climacteric women markedly in the sleep disturbances, depressed mood and anxiety domains and should not to be basically attributed to the climacteric. It is necessary that the professionals consider the need of assessment of such pathologies as complex phenomena and the literature lacks studies contemplating such dimensions.

Subthalamic deep brain stimulation modulates small fiber-dependent sensory thresholds in Parkinson's disease

The effects of deep brain stimulation of the subthalamic nucleus on nonmotor symptoms of Parkinson's disease (PD) rarely have been investigated. Among these, sensory disturbances, including chronic pain (CP), are frequent in these patients. The aim of this study was to evaluate the changes induced by deep brain stimulation in the perception of sensory stimuli, either noxious or innocuous, mediated by small or large nerve fibers. Sensory detection and pain thresholds were assessed in 25 PD patients all in the off-medication condition with the stimulator turned on or off (on- and off-stimulation conditions, respectively). The relationship between the changes induced by surgery on quantitative sensory testing, spontaneous CP, and motor abilities were studied. Quantitative sensory test results obtained in PD patients were compared with those of age-matched healthy subjects. Chronic pain was present in 72% of patients before vs 36% after surgery (P = .019). Compared with healthy subjects, PD patients had an increased sensitivity to innocuous thermal stimuli and mechanical pain, but a reduced sensitivity to innocuous mechanical stimuli. In addition, they had an increased pain rating when painful thermal stimuli were applied, particularly in the off-stimulation condition. In the on-stimulation condition, there was an increased sensitivity to innocuous thermal stimuli but a reduced sensitivity to mechanical or thermal pain. Pain provoked by thermal stimuli was reduced when the stimulator was turned on. Motor improvement positively correlated with changes in warm detection and heat pain thresholds. Subthalamic nucleus deep brain stimulation contributes to relieve pain associated with PD and specifically modulates small fiber-mediated sensations. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.

Eficácia da desativação dos pontos-gatilho miofasciais para o controle do zumbido

Dor crônica nas imediações do ouvido pode influenciar o zumbido. OBJETIVO: Investigar a eficácia da desativação de pontos-gatilho miofasciais na melhora do zumbido. MÉTODO: Ensaio clínico randomizado com 71 pacientes com zumbido e síndrome dolorosa miofascial. O Grupo Experimental (n = 37) foi submetido a 10 sessões de desativação dos pontos-gatilho miofasciais e o Grupo Controle (n = 34), a 10 sessões de desativação placebo. RESULTADOS: O tratamento do Grupo Experimental foi eficaz para o controle do zumbido (p < 0,001). Houve associação entre as melhoras de dor e zumbido (p = 0,013) e entre os lados da orelha com pior zumbido e do corpo com mais dor (p < 0,001). A presença de modulação (aumento ou diminuição) temporária do zumbido durante a palpação inicial dos pontos foi frequente em ambos os grupos, mas a diminuição temporária foi associada à melhora persistente do zumbido ao fim do tratamento (p = 0,002). CONCLUSÃO: Além da avaliação médica e audiológica, os pacientes com zumbido devem ser avaliados para: 1) presença de dor miofascial próxima à orelha; 2) lateralidade entre ambos os sintomas; 3) diminuição temporária do zumbido durante a palpação do músculo dolorido. O tratamento deste subgrupo de pacientes pode ter melhor prognóstico que os demais.

Psychometric properties of the Spanish version of the mindful attention awareness scale (MAAS) in patients with fibromyalgia

Background Mindful-based interventions improve functioning and quality of life in fibromyalgia (FM) patients. The aim of the study is to perform a psychometric analysis of the Spanish version of the Mindful Attention Awareness Scale (MAAS) in a sample of patients diagnosed with FM. Methods The following measures were administered to 251 Spanish patients with FM: the Spanish version of MAAS, the Chronic Pain Acceptance Questionnaire, the Pain Catastrophising Scale, the Injustice Experience Questionnaire, the Psychological Inflexibility in Pain Scale, the Fibromyalgia Impact Questionnaire and the Euroqol. Factorial structure was analysed using Confirmatory Factor Analyses (CFA). Cronbach's α coefficient was calculated to examine internal consistency, and the intraclass correlation coefficient (ICC) was calculated to assess the test-retest reliability of the measures. Pearson’s correlation tests were run to evaluate univariate relationships between scores on the MAAS and criterion variables. Results The MAAS scores in our sample were low (M = 56.7; SD = 17.5). CFA confirmed a two-factor structure, with the following fit indices [sbX2 = 172.34 (p < 0.001), CFI = 0.95, GFI = 0.90, SRMR = 0.05, RMSEA = 0.06. MAAS was found to have high internal consistency (Cronbach’s α = 0.90) and adequate test-retest reliability at a 1–2 week interval (ICC = 0.90). It showed significant and expected correlations with the criterion measures with the exception of the Euroqol (Pearson = 0.15). Conclusion Psychometric properties of the Spanish version of the MAAS in patients with FM are adequate. The dimensionality of the MAAS found in this sample and directions for future research are discussed.

Dor crônica pós-cesariana. Influência da técnica anestésico-cirúrgica e da analgesia pós-operatória

JUSTIFICATIVA E OBJETIVOS: O Brasil ocupa o segundo lugar entre os países com maiores taxas de cesariana no mundo. Pouco se sabe a respeito das consequências futuras desse procedimento sobre a saúde materna. Este estudo investigou a influência da técnica anestésico-cirúrgica e da analgesia pós-operatória no aparecimento de dor crônica após três meses da cesariana. MÉTODO: Este estudo prospectivo randomizado foi feito em 443 pacientes submetidas a cesariana (eletiva e urgente), com diferentes doses de bupivacaína 0,5% hiperbárica e opioides na raquianestesia. Os grupos foram: G1- 8 mg bupivacaína hiperbárica + 2,5 mg sufentanil + 100 mg morfina; G2- 10 mg bupivacaína hiperbárica + 2,5 mg sulfentanil + 100 mg morfina; G3- 12,5 mg bupivacaína hiperbárica + 100 mg morfina; G4- 15 mg bupivacaína hiperbárica + 100 mg morfina; G5- 12,5 mg bupivacaína hiperbárica + 100 mg morfina (sem anti-inflamatório perioperatório). Dor em repouso e em movimento foram avaliadas no pós-operatório imediato. Contato telefônico foi feito, após três meses do procedimento cirúrgico, para identificação das pacientes com dor crônica. RESULTADOS: A incidência de dor crônica nos grupos foi: G1 = 20%; G2 = 13%; G3 = 7,1%; G4 = 2,2% e G5 = 20,3%. Pacientes que referiram escores de dor mais elevados no período pós-operatório tiveram maior incidência de dor crônica (p < 0,05). CONCLUSÃO: A incidência de dor crônica diminui com o emprego de doses maiores de anestésicos locais e uso de anti-inflamatórios não hormonais. Escores mais elevados de dor no período pós-operatório tiveram associação com aparecimento de dor crônica após três meses da cesariana.

Cefaleia em pacientes com dor crônica entrevistados na Unidade de Dor do Hospital Central de Maputo, Moçambique

JUSTIFICATIVA E OBJETIVOS: Nos últimos anos, a abordagem da dor crônica em Maputo, capital de Moçambique, ganhou espaço, com a construção da Unidade de Dor do Hospital Central. No continente africano existem poucos estudos epidemiológicos sobre dor crônica. Em Moçambique, nenhum estudo prévio foi publicado. O objetivo deste estudo foi descrever e analisar as características da cefaleia em pacientes com dor crônica entrevistados no referido hospital. MÉTODO: Participantes com dor crônica de acordo com critérios da International Association for the Study of Pain (IASP), maiores de 18 anos, fluentes em português foram incluídos. Dados demográficos, características da dor crônica e presença de cefaleia foram investigados. RESULTADOS: Cento e dezoito pacientes foram avaliados. Destes, 79 (66,9%) eram mulheres e 39 (33,1%) eram homens, com média de idade de 52,4 anos. Presença de cefaleia foi frequente entre estes pacientes (53/ 44,9%) embora esta não fosse necessariamente sua dor principal. Cefaleia foi o principal segundo sítio de dor. Migrânea foi diagnóstico em 14 (11,9%) pacientes, cefaleia tensional em 28 (23,8%), cefaleia cervicogênica em 9 (7,6%). CONCLUSÃO: Os dados revelam que nos pacientes com dor crônica na Unidade de Dor do Hospital Central de Maputo há prevalência de cefaleias semelhante àquela descrita na população em geral por outros estudos.

Dor crônica refratária de tornozelo controlada com radiofrequência pulsada: relato de caso

JUSTIFICATIVA E OBJETIVOS: A radiofrequência (RF) é uma corrente alternada com frequência de oscilação de 500.000 Hz, que tem sido usada com sucesso no tratamento de algumas morbidades que cursam com dor crônica. O objetivo deste relato de caso foi mostrar o uso bem sucedido da RF pulsátil do nervo sural para o tratamento de dor crônica no tornozelo. RELATO DO CASO: Paciente do sexo feminino, 60 anos, que há 5 anos apresentava dor em tornozelo direito, refratária ao tratamento com opioides, anti-inflamatório não esteroides (AINES), dipirona, antidepressivos e anticonvulsivantes, fisioterapia, infiltrações localizadas, acupuntura e palmilha. A paciente foi submetida a aplicação de RF pulsátil de nervo sural direito. O local da inserção da agulha foi na linha entre o tendão de Aquiles e maléolo lateral, região inicial de tendão de Aquiles e final dos músculos sóleo e gastrocnêmio. A estimulação sensitiva para identificação do nervo sural foi com 0,5 volts e 50 Hz. A corrente pulsátil foi aplicada durante 140 segundos com 45 volts com temperatura de até 42º C. Foram realizadas duas aplicações, ocorrendo melhora de cerca de 80% da dor, permitindo que a paciente pudesse deambular ou permanecer em pé, sem maiores dificuldades. CONCLUSÃO: A RF pulsátil do nervo sural pode ser uma opção para o controle das dores crônicas em tornozelo.

Assessment of depression in medical patients: a systematic review of the utility of the beck depression inventory-II

To perform a systematic review of the utility of the Beck Depression Inventory for detecting depression in medical settings, this article focuses on the revised version of the scale (Beck Depression Inventory-II), which was reformulated according to the DSM-IV criteria for major depression. We examined relevant investigations with the Beck Depression Inventory-II for measuring depression in medical settings to provide guidelines for practicing clinicians. Considering the inclusion and exclusion criteria seventy articles were retained. Validation studies of the Beck Depression Inventory-II, in both primary care and hospital settings, were found for clinics of cardiology, neurology, obstetrics, brain injury, nephrology, chronic pain, chronic fatigue, oncology, and infectious disease. The Beck Depression Inventory-II showed high reliability and good correlation with measures of depression and anxiety. Its threshold for detecting depression varied according to the type of patients, suggesting the need for adjusted cut-off points. The somatic and cognitive-affective dimension described the latent structure of the instrument. The Beck Depression Inventory-II can be easily adapted in most clinical conditions for detecting major depression and recommending an appropriate intervention. Although this scale represents a sound path for detecting depression in patients with medical conditions, the clinician should seek evidence for how to interpret the score before using the Beck Depression Inventory-II to make clinical decisions

Entwicklung eines Screeningverfahrens zum simultanen Nachweis von Opioiden in menschlichen Körperflüssigkeiten, Geweben und Haaren für forensisch-toxikologische und klinische Untersuchungen

In den letzten Jahren stieg in Deutschland der Gebrauch bzw. Missbrauch von Opioid-Analgetika zunehmend an. Das entwickelte Verfahren sollte unter Einbeziehung neuer Substanzen möglichst viele verschiedene Opioide und auch ihre pharmakologisch aktiven Stoffwechselprodukte berücksichtigen.rnVor Analyse wurden Blut-, Serum- oder Urinproben mit Phosphatpuffer versetzt und mittels Festphasenextraktion an C18-Säulenmaterial aufgearbeitet. Post-Mortem-Gewebematerial wurde mit isotonischer Kochsalzlösung versetzt, homogenisiert und anschließend durch eine Festphasenextraktion aufgereinigt. Haarproben wurden nach Zerkleinerung mit Methanol unter Ultrabeschallung extrahiert. Die Flüssigchromatographie gekoppelt mit Tandem-Massenspektrometrie (Elektrosprayionisation im positiven Modus) erwies sich als geeignetes Verfahren für die simultane Bestimmung der Opioide in biologischem Probenmaterial (Körperflüssigkeiten, Gewebe und Haaren). Der Multi-Analyt Assay erlaubt die quantitative Analyse von 35 verschiedenen Opioiden. Die Analyten wurden durch eine Phenyl-Hexyl Säule und einen Wasser/Acetonitril Gradienten durch eine UPLC 1290 Infinity gekoppelt mit einem 6490 Triple Quadrupol von Agilent Technologies separiert.rnDie LC/MS Methode zur simultanen Bestimmung von 35 Opioiden in Serum und Haaren wurde nach den Richtlinien der Gesellschaft für Toxikologische und Forensische Chemie (GTFCh) validiert. Im Fall der Serumvalidierung lagen die Nachweisgrenzen zwischen 0.02 und 0.6 ng/ml und die Bestimmungsgrenzen im Bereich von 0.1 bis 2.0 ng/ml. Die Kalibrationskurven waren für die Kalibrationslevel 1 bis 6 linear. Wiederfindungsraten lagen für alle Verbindungen zwischen 51 und 88 %, außer für Alfentanil, Bisnortiliidn, Pethidin und Morphin-3-Glucuronid. Der Matrixeffekt lag zwischen 86 % (Ethylmorphin) und 105 % (Desomorphin). Für fast alle Analyten konnten akzeptable Werte bei der Bestimmung der Genauigkeit und Richtigkeit nach den Richtlinien der GTFCh erhalten werden. Im Fall der Validierung der Haarproben lagen die Nachweisgrenzen zwischen 0.004 und 0.6 ng/Probe und die Bestimmungsgrenzen zwischen 0.1 ng/Probe und 2.0 ng/Probe. Für die Kalibrationslevel 1 bis 6 waren alle Kalibrationsgeraden linear. Die Wiederfindungsraten lagen für die Opioide im Bereich von 73.5 % (Morphin-6-Glucuronid) und 114.1 % (Hydrocodon). Die Werte für die Bestimmung der Richtigkeit lagen zwischen - 6.6 % (Methadon) und + 11.7 % (Pholcodin). Präzisionsdaten wurden zwischen 1.0 % für Dextromethorphan und 11.5 % für Methadon ermittelt. Die Kriterien der GTFCh konnten bei Ermittlung des Matrixeffekts für alle Substanzen erfüllt werden, außer für 6-Monoacetylmorphin, Bisnortilidin, Meperidin, Methadon, Morphin-3-glucuronid, Morphin-6-glucuronid, Normeperidin, Nortilidin und Tramadol.rnZum Test des Verfahrens an authentischem Probenmaterial wurden 206 Proben von Körperflüssigkeiten mit Hilfe der simultanen LC/MS Screening Methode untersucht. Über 150 Proben wurden im Rahmen von forensisch-toxikologischen Untersuchungen am Instituts für Rechtsmedizin Mainz analysiert. Dabei konnten 23 der 35 Opioide in den realen Proben nachgewiesen werden. Zur Untersuchung der Pharmakokinetik von Opioiden bei Patienten der anästhesiologischen Intensivstation mit Sepsis wurden über 50 Blutproben untersucht. Den Patienten wurde im Rahmen einer klinischen Studie einmal täglich vier Tage lang Blut abgenommen. In den Serumproben wurde hauptsächlich Sufentanil (0.2 – 0.8 ng/ml in 58 Fällen) und Piritramid (0.4 – 11 ng/ml in 56 Fällen) gefunden. Außerdem wurden die Proben von Körperflüssigkeiten und Gewebe von 13 verschiedenen Autopsiefällen mit Hilfe des Multi-Analyt Assays auf Opioide untersucht.rnIn einem zweiten Schritt wurde die Extraktions- und Messmethode zur Quantifizierung der 35 Opioide am Forensic Medicine Center in Ho Chi Minh City (Vietnam) etabliert. Insgesamt wurden 85 Herzblutproben von Obduktionsfällen mit Verdacht auf Opiatintoxikation näher untersucht. Der überwiegende Teil der untersuchten Fälle konnte auf eine Heroin- bzw. Morphin-Vergiftung zurückgeführt werden. Morphin wurde in 68 Fällen im Konzentrationsbereich 1.7 – 1400 ng/ml und der Heroinmetabolit 6-Monoactetylmorphin in 34 Fällen (0.3 – 160 ng/ml) nachgewiesen werden.rnSchließlich wurden noch 15 Haarproben von Patienten einer psychiatrischen Klinik, die illegale Rauschmittel konsumiert hatten, mit Hilfe der simultanen Opioid-LC/MS Screeningmethode gemessen. Die Ergebnisse der Untersuchung wurden mit früheren Auswertungen von gaschromatographischen Analysen verglichen. Es zeigte sich eine weitgehende Übereinstimmung der Untersuchungsergebnisse für die Opioide 6-Monoacetylmorphin, Morphin, Codein, Dihydrocodein und Methadon. Mit der LC/MS Methode konnten weitere Substanzen, wie zum Beispiel Bisnortilidin, Dextromethorphan und Tramadol in den Haarproben gefunden werden, die bislang nicht entdeckt worden waren.rn

In vivo assessment of HCN channel current (I(h)) in human motor axons

The "Trond" protocol of nerve excitability tests has been used widely to assess axonal function in peripheral nerve. In this study, the routine Trond protocol was expanded to refine assessment of cAMP-dependent, hyperpolarization-activated current (I(h)) activity. I(h) activity is generated by hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels in response to hyperpolarization. It limits activity-dependent hyperpolarization, contributes to neuronal automaticity, and is implicated in chronic pain states. Published data regarding I(h) activity in motor nerve are scant. We used additional strong, prolonged hyperpolarizing conditioning stimuli in the threshold electrotonus component of the Trond protocol to demonstrate the time-course of activation of I(h) in motor axons. Fifteen healthy volunteers were tested on four occasions during 1 week. I(h) action was revealed in the threshold electrotonus by the limiting and often reversal, after about 100 ms, of the threshold increase caused by strong hyperpolarizing currents. Statistical analysis by repeated-measures analysis of variance enabled confidence limits to be established for variation between subjects and within subjects. The results demonstrate that, of all the excitability parameters, those dependent on I(h) were the most characteristic of an individual, because variance between subjects was more than four times the variance within subjects. This study demonstrates a reliable method for in vivo assessment of I(h,) and also serves to document the normal variability in nerve excitability properties within subjects.

Expression of the nociceptin precursor and nociceptin receptor is modulated in cancer and septic patients

A role of nociceptin and its receptor (NOP) in pain and immune function has been suggested. The hypothesis was that mRNA expression of NOP and the nociceptin precursor pre-pronociceptin (pN/OFQ) in peripheral blood cells differs in end-stage cancer patients suffering from chronic pain and septic intensive care unit (ICU) patients compared with healthy controls.

Prospective randomized trial comparing sutured with sutureless mesh fixation for Lichtenstein hernia repair: long-term results

Following Lichtenstein hernia repair, up to 25% of patients experience prolonged postoperative and chronic pain as well as discomfort in the groin. One of the underlying causes of these complaints are the compression or irritation of nerves by the sutures used to fixate the mesh. We compared the level and rate of chronic pain in patients operated with the classical Lichtenstein technique fixated by sutures to patients with sutureless mesh fixation technique.

Transcutaneous electrostimulation for osteoarthritis of the knee

BACKGROUND: Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in the elderly. Transcutaneous electrical nerve stimulation (TENS), interferential current stimulation and pulsed electrostimulation are used widely to control both acute and chronic pain arising from several conditions, but some policy makers regard efficacy evidence as insufficient. OBJECTIVES: To compare transcutaneous electrostimulation with sham or no specific intervention in terms of effects on pain and withdrawals due to adverse events in patients with knee osteoarthritis. SEARCH STRATEGY: We updated the search in CENTRAL, MEDLINE, EMBASE, CINAHL and PEDro up to 5 August 2008, checked conference proceedings and reference lists, and contacted authors. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared transcutaneously applied electrostimulation with a sham intervention or no intervention in patients with osteoarthritis of the knee. DATA COLLECTION AND ANALYSIS: We extracted data using standardised forms and contacted investigators to obtain missing outcome information. Main outcomes were pain and withdrawals or dropouts due to adverse events. We calculated standardised mean differences (SMDs) for pain and relative risks for safety outcomes and used inverse-variance random-effects meta-analysis. The analysis of pain was based on predicted estimates from meta-regression using the standard error as explanatory variable. MAIN RESULTS: In this update we identified 14 additional trials resulting in the inclusion of 18 small trials in 813 patients. Eleven trials used TENS, four interferential current stimulation, one both TENS and interferential current stimulation, and two pulsed electrostimulation. The methodological quality and the quality of reporting was poor and a high degree of heterogeneity among the trials (I(2) = 80%) was revealed. The funnel plot for pain was asymmetrical (P < 0.001). The predicted SMD of pain intensity in trials as large as the largest trial was -0.07 (95% CI -0.46 to 0.32), corresponding to a difference in pain scores between electrostimulation and control of 0.2 cm on a 10 cm visual analogue scale. There was little evidence that SMDs differed on the type of electrostimulation (P = 0.94). The relative risk of being withdrawn or dropping out due to adverse events was 0.97 (95% CI 0.2 to 6.0). AUTHORS' CONCLUSIONS: In this update, we could not confirm that transcutaneous electrostimulation is effective for pain relief. The current systematic review is inconclusive, hampered by the inclusion of only small trials of questionable quality. Appropriately designed trials of adequate power are warranted.