Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2021-000804-39 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Ministry of Science and Innovation, Spain | OTHER_GOV |
| Health Research Institute of Santiago de Compostela - IDIS (Recruitment support) | UNKNOWN |
| Fundación Biomédica Galicia Sur (Recruitment support) | UNKNOWN |
Not provided
Not provided
Not provided
Refractory chronic pain represents a serious and limiting health condition which does not respond to standard pharmacological therapy. Thus, it emerges the necessity of new techniques to treat these group of diseases, such as the transcranial electrical stimulation (tES). This procedure induces a low-intensity electrical current through the scalp to modify the excitability of brain cells, thus facilitating changes in neural networks which may be dysfunctional in some chronic pain patients.
The main objective of this research is to test the efficacy of two tES techniques, differentiated by applying direct or alternant electrical current, to reduce the pain intensity and to increase pain thresholds of these patients. Besides, intervention is implemented at home for patients themselves thanks to a portable and convenient stimulator device, after one training session provided by technicians. Researches can supervise the compliance of the treatment remotely, as the stimulator has a permanent connection with their computers. A home-based approach means a more comfortable and accessible treatment alternative for patients, since they do not have to attend to clinics everyday to receive the stimulation; the advantages become even more relevant in the pandemic context, since the risk of being infected is radically minimized.
Despite the main purpose is to test the efficacy of tES to improve the pain suffered by patients, many other areas are considered as secondary end points for being intrinsically linked or affected by the disease, such as the interference in daily tasks provoked by pain, mood disorders (depression/anxiety), fatigue, life quality, physical functioning and sleep quality; these last two variables are measured with actigraph wristwatches, apart from specific questionnaires. Lastly, endogenous modulatory pain mechanisms are examined through sensory tests, namely Conditioned Pain Modulation and Temporal Summation of pain.
This work aims to provide answers to the refractory chronic pain challenge. Pain is defined as refractory when multiple evidence-based biomedical therapies have failed to reach treatment goals that may include adequate pain reduction and/or improvement in daily functioning, even after appropriately assessing and addressing those psychosocial factors that could influence pain outcomes. In this sense, on the one hand, the study focus on detecting central biomarkers of pain modulation and processing which will contribute to improving knowledge of the mechanisms of pain chronification and the diagnosis procedure. On the other hand, given the low efficacy of pharmacological or non-pharmacological therapies for the patients studied, the efficacy of new therapeutic alternatives (tES) is explored. In short, the project will allow the transfer of knowledge to clinical practice in several aspects, such as diagnosis or treatment.
Therefore, the research aims to test the role of defective central pain modulation/processing as explanatory mechanisms for chronic pain. A second main objective is to test the efficacy of transcranial electric stimulation (tES) to modify dysfunction of central mechanism of pain, and to improve symptoms and quality of life in refractory chronic pain patients.
To achieve this, the investigators will select valid and reliable instruments to assess pain and comorbid symptoms in chronic pain patients and the most sensitive outcome measures to assess tES treatment efficacy. Sensory testing paradigms, namely Conditioned Pain Modulation, Temporal Summation of Second Pain and pain-related evoked potentials using electroencephalographic recordings, will act as biomarkers which are proposed to correlate with the severity of the chronic pain disease or some of their symptoms, and also as predictors of the treatment outcome.
Total sample includes 120 patients with refractory pharmaco-resistant pain, attended at the Pain Units of two Public Galician Hospitals (36 male, 84 female).
The study is expected to contribute to detection and preventive measures of future pain, and diagnosis of chronic pain disorders, improving prognosis and development of feasible patient-centered interventions, providing new directions for future research on pain.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Transcranial direct current stimulation (tDCS) | Active Comparator | Fifteen stimulation sessions applied with a daily frequency during an uninterrupted period of time which comprises just over two weeks. Current intensity of 2mA is applied during 20 minutes at the left M1, with anodal electrode placed in C3 and cathodal in FP2, following the International 10-20 EEG System. Ramp-up and ramp-down comprises 15 seconds at the beginning and end of the stimulation period. |
|
| Transcranial alternant current stimulation (tACS) | Active Comparator | Fifteen stimulation sessions applied with a daily frequency during an uninterrupted period of time which comprises just over two weeks. Two electrodes will be placed at F3 and F4 and connected together for 10-Hz tACS (or the frequency which shows best sensitivity or specificity), and one electrode at Pz will be the return electrode. This setting is used to stimulate the somatosensory cortical region. Stimulation will last for 20 minutes, with a ramp-up and ramp-down of 15 seconds at the beginning and end of the session. |
|
| Sham stimulation | Placebo Comparator | The electrode montage will be either the tDCS (for half of the participants) or the tACS montage (for the other half), and we will just apply the current at the ramps terms, but no current in the interval between the ramps which practically comprises the whole session. As for the two other group, fifteen sham stimulation sessions will be daily scheduled in a non-interrupted period of two weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transcranial electrical stimulation | Device | By applying a low current over the cortex through the scalp, this technique can excite or inhibit the neural activity, thus modulating brain processes like pain perception and inducing relatively sustained changes in cortical excitability and neuroplasticity. Home-based transcranial electrical stimulation device consists of a custom headgear with fixed electrode sites and built-in cabling made for a simplistic setup for tDCS/tACS stimulation. Systems are equipped with strict dose control feature that provide reliable control over the intensity and timing of stimulation, turning these devices into a feasible and safe clinical alternative. The equipment is specifically designed for easy and simplistic self-setup and allows the researchers to remotely check the position of electrodes and also monitor the stimulation session. |
| Measure | Description | Time Frame |
|---|---|---|
| Self-reported pain intensity | Participants must evaluate the intensity of their pain using an online version of a Numerical Rating Scale of eleven points (0-10), so that the higher the score is, the worse the pain is. | Pre-treatment measure is the average of pain intensity of fifteen days previous to treatment; whereas the post-treatment measure is the average of fifteen days after treatment have finished |
| Measure | Description | Time Frame |
|---|---|---|
| Global severity of chronic pain syndrome | Composed index about the gravity of the chronic pain condition, taking into account several parameters as social and professional limitations due to pain, frequency and intensity of pain crisis, among others. The severity of chronic pain syndrome is assessed with global and subscales scores of Multidimensional Pain Inventory (MPI). Higher scores are indicative of worse health condition. |
| Measure | Description | Time Frame |
|---|---|---|
| Endogenous pain inhibition response | Inhibitory pain system will be assessed through the Conditioned Pain Modulation (CPM) paradigm, which consists of the reduction of the pain provoked by a given noxious stimulus (i.e., test stimulus) when another painful stimulus (i.e., conditioning stimulus) is applied to a remote area (i.e., pain inhibits pain). Tentatively, we will use the cold water immersion of the non-dominant hand as conditioning stimuli; whereas the test stimuli will be the pressure pain thresholds using a digital handhold algometer, which puts progressively heavier pressure over the lateral area of dominant forearm. Differences in pressure pain threshold between the standard condition and when the CS is applied is assumed as an index of pain inhibitory response. Negative values are indicative of a greater pain inhibitory response. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| MarÃa Teresa Carrillo de la Peña, PhD | Contact | +34 625 76 32 25 | mteresa.carrillo@usc.es | |
| J. Antonio Vázquez Millán | Contact | joseantonio.vazquez.millan@rai.usc.es |
| Name | Affiliation | Role |
|---|---|---|
| MarÃa Teresa Carrillo de la Peña | University of Santiago de Compostela | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Santiago de Compostela | Recruiting | Santiago de Compostela | A Coruña | 15701 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30268803 | Background | Ahn S, Prim JH, Alexander ML, McCulloch KL, Frohlich F. Identifying and Engaging Neuronal Oscillations by Transcranial Alternating Current Stimulation in Patients With Chronic Low Back Pain: A Randomized, Crossover, Double-Blind, Sham-Controlled Pilot Study. J Pain. 2019 Mar;20(3):277.e1-277.e11. doi: 10.1016/j.jpain.2018.09.004. Epub 2018 Sep 27. | |
| 28709880 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 1, 2021 | Jul 17, 2021 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D059350 | Chronic Pain |
| D005356 | Fibromyalgia |
| D001168 | Arthritis |
| D010003 | Osteoarthritis |
| D017116 | Low Back Pain |
| D008881 | Migraine Disorders |
| D001008 | Anxiety Disorders |
| D003863 | Depression |
| D012893 | Sleep Wake Disorders |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D065908 | Transcranial Direct Current Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D003295 | Convulsive Therapy |
| D013000 | Psychiatric Somatic Therapies |
Not provided
Not provided
Participants will be randomly assigned to one of three treatment groups (40% active tDCS; 40% Active tACS; 20% Sham). Patients receiving sham stimulation will act as the control group.
Not provided
Not provided
Portable devices for applying the transcranial electrical stimulation are equipped with a software which allows a double-blinded procedure. The same computer program is in charge of randomly allocating patients to one of the three treatment groups. Thus, nor the researchers neither the participants will know what kind of stimulation is receiving each of them.
|
|
| Participants will complete MPI one or two days before the treatment onset, and one or two days after treatment ending. |
| Pressure pain threshold | Pressure pain threshold is defined as the minimum force necessary to induce pain in the participant, measured using a manual algometer and operationalized in kPa. | Pressure pain thresholds will be assessed in face-to-face laboratory sessions, which would take place one or two days before the treatment onset and one or two days after treatment ending. |
| Heat pain threshold | Heat pain threshold is stablished as the temperature, measured in degrees Celsius, at which participant starts to feel pain, using a thermal stimulator. | Heat pain thresholds will be assessed in face-to-face laboratory sessions, which would take place one or two days before the treatment onset and one or two days after treatment ending. |
| Interference in daily living caused by pain | Subscales of Multidimensional Pain Inventory (MPI) are used to evaluate whether patients usually leave undone or are not capable to do some daily activities and tasks due to the pain they suffer from. The test consists of a numerical rating scale of seven points (0-6), so that the higher the score is, the more pronounced is the interference due to pain. | Pain interference will be assessed in face-to-face laboratory sessions, which would take place one or two days before the treatment onset and one or two days after treatment ending. |
| Life quality | General health status considering physical, emotional and social functionality, as well as physical and mental health. Life quality is measured using the Short Form-36 Health Survey (SF-36). Higher scores are indicative of better health condition. | Life quality will be assessed one or two days before the treatment onset and one or two days after treatment ending. |
| Physical condition and functioning | Involvement and time-spent in physical activities or exercises. | Estimations about daily energy expenditure, based on sedentary and activity bouts are recorded with wristband actigraphs which participants must wear during the whole research period. |
| Sleep quality and disturbances | Sleep habits of participants and the degree in which they perceive that sleep as restorative. Sleep quality is measured using the Pittsburgh Sleep Quality Index (PSQI), a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Higher scores are indicative of poorer sleep quality. | Participants will complete PQSI at two time-points, this is, one or two days before the treatment onset and one or two days after treatment ending. |
| Sleep quality and disturbances | Sleep habits of participants, as total sleep time. This sleep parameter is measured using the data recorded for wristband actigraphs which participants must wear during the whole research period. | Wristband actigraph are given to patients fifteen days before the treatment onset, so sleep habits are monitorized since that moment, until fifteen days after treatment have finished |
| Pain unpleasantness | Affective component of pain, which refers to the discomfort or distress which pain provokes in patients. Participants must evaluate the discomfort produced by pain using an online version of a Numerical Rating Scale of eleven points (0-10), so that the higher the score is, the more stressful the pain is. | Pre-treatment measure is the average of pain unpleasantness obtained from fifteen daily assessments previous to treatment; whereas the post-treatment measure is the average obtained from the fifteen days after treatment have finished |
| Mood disorders | Depressive and anxiety symptomatology which can concur with chronic pain conditions. Mood alterations are measured using the Hospital Anxiety and Depression Scale (HADS). Higher scores are indicative of a worse mood state. | Participants will complete HADS at two time-points, this is, one or two days before the treatment onset and one or two days after treatment ending. |
| Anxiety | General anxiety level are evaluated with a daily frequency using an online version of a Numerical Rating Scale of eleven points (0-10), so that the higher the score is, the higher the anxiety level is. | Pre-treatment measure is the average of anxiety levels obtained from fifteen daily assessments previous to treatment; whereas the post-treatment measure is the average obtained from the fifteen days after treatment have finished |
| Fatigue | Tiredness which may result in difficulties to perform physical or psychological tasks. Fatigue and its consequences are measured using the Modified Impact Fatigue Scale (MFIS). Numerical Rating Scales of eleven points (0-10) are also used to assess daily fatigue levels. In both cases, higher scores are indicative of a greater fatigue. | Fatigue is registered with a daily frequency since the fifteen days before the treatment onset, until fifteen days after treatment ending. Participants will complete the MFIS at two time-points, this is, one or two days before and after treatment. |
| Caregiver burden | Stress levels which are subjected the caregivers of chronic pain patients are evaluated through the Zarit Burden Interview (ZBI) to assess if tES treatment means a reduction in burden derived from caring tasks. Higher scores are indicative of a more pronounced caregiver burden. | Caregivers are invited to a face-to-face interview with researchers one or two days before the treatment onset and one or two days after treatment ending. |
| Global satisfaction with treatment and self-perceived improvement | Patients are asked to rate their satisfaction with the tES treatment and whether they believe it has helped to improve their health status, using an ad-hoc designed questionnaire. | Participants will evaluate their satisfaction with treatment a few days after it had finished. |
| CPM procedure will be performed at two time-points, this is, one or two days before and after treatment, in order to assess if tES treatment is capable of restoring any dysfunction in this inhibitory pain network. |
| Endogenous pain facilitation response | Amplifier pain system will be assessed through the Temporal Summation of Second Pain (TSSP) paradigm, which consists of the augmentation of subjective pain sensations due to the application of repeated noxious stimuli over the same corporal area, even when those stimuli are equal in terms of intensity and duration. Positive values are indicative of a greater pain facilitation score. | TSSP procedure will be performed at two time-points, this is, one or two days before and after treatment, in order to assess if tES treatment is capable of restoring any dysfunction in this facilitatory pain network. |
| Electrical brain activity over diverse conditions | Using the electroencephalography, we will capture the brain default mode network of chronic pain patients. Besides, we will register the evoked potentials elicited by diverse types of noxious heat-stimuli, as they may be reflecting how nociceptive signals are processed by brain. We purport to make a time-frequency and connectivity analysis of the EEG paying special attention to those key frequency bands involved in nociceptive perception, such as theta, alpha and gamma bands. | EEG will be registered at two time-points, this is, one or two days before and one or two days after treatment. |
| Antal A, Alekseichuk I, Bikson M, Brockmoller J, Brunoni AR, Chen R, Cohen LG, Dowthwaite G, Ellrich J, Floel A, Fregni F, George MS, Hamilton R, Haueisen J, Herrmann CS, Hummel FC, Lefaucheur JP, Liebetanz D, Loo CK, McCaig CD, Miniussi C, Miranda PC, Moliadze V, Nitsche MA, Nowak R, Padberg F, Pascual-Leone A, Poppendieck W, Priori A, Rossi S, Rossini PM, Rothwell J, Rueger MA, Ruffini G, Schellhorn K, Siebner HR, Ugawa Y, Wexler A, Ziemann U, Hallett M, Paulus W. Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol. 2017 Sep;128(9):1774-1809. doi: 10.1016/j.clinph.2017.06.001. Epub 2017 Jun 19. |
| 20418016 | Background | Arendt-Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, Graven-Nielsen T. Sensitization in patients with painful knee osteoarthritis. Pain. 2010 Jun;149(3):573-581. doi: 10.1016/j.pain.2010.04.003. Epub 2010 Apr 24. |
| 16095934 | Background | Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006 May;10(4):287-333. doi: 10.1016/j.ejpain.2005.06.009. Epub 2005 Aug 10. |
| 23719569 | Background | Bushnell MC, Ceko M, Low LA. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci. 2013 Jul;14(7):502-11. doi: 10.1038/nrn3516. Epub 2013 May 30. |
| 29391478 | Background | Choe MK, Lim M, Kim JS, Lee DS, Chung CK. Disrupted Resting State Network of Fibromyalgia in Theta frequency. Sci Rep. 2018 Feb 1;8(1):2064. doi: 10.1038/s41598-017-18999-z. |
| 28884750 | Background | Davis KD, Flor H, Greely HT, Iannetti GD, Mackey S, Ploner M, Pustilnik A, Tracey I, Treede RD, Wager TD. Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations. Nat Rev Neurol. 2017 Oct;13(10):624-638. doi: 10.1038/nrneurol.2017.122. Epub 2017 Sep 8. |
| 29567583 | Background | De Keyser R, van den Broeke EN, Courtin A, Dufour A, Mouraux A. Event-related brain potentials elicited by high-speed cooling of the skin: A robust and non-painful method to assess the spinothalamic system in humans. Clin Neurophysiol. 2018 May;129(5):1011-1019. doi: 10.1016/j.clinph.2018.02.123. Epub 2018 Mar 8. |
| 29093972 | Background | de Tommaso M, Ricci K, Libro G, Vecchio E, Delussi M, Montemurno A, Lopalco G, Iannone F. Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials. Pain Res Treat. 2017;2017:9747148. doi: 10.1155/2017/9747148. Epub 2017 Sep 28. |
| 25530229 | Background | Duenas M, Salazar A, Ojeda B, Fernandez-Palacin F, Mico JA, Torres LM, Failde I. A nationwide study of chronic pain prevalence in the general spanish population: identifying clinical subgroups through cluster analysis. Pain Med. 2015 Apr;16(4):811-22. doi: 10.1111/pme.12640. Epub 2014 Dec 19. |
| 15621359 | Background | Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, Kerns RD, Stucki G, Allen RR, Bellamy N, Carr DB, Chandler J, Cowan P, Dionne R, Galer BS, Hertz S, Jadad AR, Kramer LD, Manning DC, Martin S, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robbins W, Robinson JP, Rothman M, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Wernicke J, Witter J; IMMPACT. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005 Jan;113(1-2):9-19. doi: 10.1016/j.pain.2004.09.012. No abstract available. |
| 28758313 | Background | Fallon N, Chiu Y, Nurmikko T, Stancak A. Altered theta oscillations in resting EEG of fibromyalgia syndrome patients. Eur J Pain. 2018 Jan;22(1):49-57. doi: 10.1002/ejp.1076. Epub 2017 Jul 31. |
| 31365469 | Background | Fernandes C, Pidal-Miranda M, Samartin-Veiga N, Carrillo-de-la-Pena MT. Conditioned pain modulation as a biomarker of chronic pain: a systematic review of its concurrent validity. Pain. 2019 Dec;160(12):2679-2690. doi: 10.1097/j.pain.0000000000001664. |
| 25547149 | Background | Frohlich F, Sellers KK, Cordle AL. Targeting the neurophysiology of cognitive systems with transcranial alternating current stimulation. Expert Rev Neurother. 2015 Feb;15(2):145-67. doi: 10.1586/14737175.2015.992782. Epub 2014 Dec 30. |
| 31048636 | Background | Gonzalez-Villar AJ, Arias M, Carrillo-de-la-Pena MT. Brain Electrical Activity Associated With Visual Attention and Reactive Motor Inhibition in Patients With Fibromyalgia. Psychosom Med. 2019 May;81(4):380-388. doi: 10.1097/PSY.0000000000000677. |
| 21187217 | Background | Jensen MP, Moore MR, Bockow TB, Ehde DM, Engel JM. Psychosocial factors and adjustment to chronic pain in persons with physical disabilities: a systematic review. Arch Phys Med Rehabil. 2011 Jan;92(1):146-60. doi: 10.1016/j.apmr.2010.09.021. |
| 23273836 | Background | Hu L, Peng W, Valentini E, Zhang Z, Hu Y. Functional features of nociceptive-induced suppression of alpha band electroencephalographic oscillations. J Pain. 2013 Jan;14(1):89-99. doi: 10.1016/j.jpain.2012.10.008. |
| 15162342 | Background | Keefe FJ, Rumble ME, Scipio CD, Giordano LA, Perri LM. Psychological aspects of persistent pain: current state of the science. J Pain. 2004 May;5(4):195-211. doi: 10.1016/j.jpain.2004.02.576. |
| 11098101 | Background | Kosek E, Ordeberg G. Lack of pressure pain modulation by heterotopic noxious conditioning stimulation in patients with painful osteoarthritis before, but not following, surgical pain relief. Pain. 2000 Oct;88(1):69-78. doi: 10.1016/S0304-3959(00)00310-9. |
| 21574899 | Background | Langley PC, Ruiz-Iban MA, Molina JT, De Andres J, Castellon JR. The prevalence, correlates and treatment of pain in Spain. J Med Econ. 2011;14(3):367-80. doi: 10.3111/13696998.2011.583303. Epub 2011 May 17. |
| 27865707 | Background | Lefaucheur JP. A comprehensive database of published tDCS clinical trials (2005-2016). Neurophysiol Clin. 2016 Dec;46(6):319-398. doi: 10.1016/j.neucli.2016.10.002. Epub 2016 Nov 17. |
| 22981090 | Background | Lewis GN, Rice DA, McNair PJ. Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J Pain. 2012 Oct;13(10):936-44. doi: 10.1016/j.jpain.2012.07.005. Epub 2012 Sep 13. |
| 19204274 | Background | Alappat JJ. Motor cortex stimulation for chronic pain: systematic review and meta-analysis of the literature. Neurology. 2009 Feb 10;72(6):577; author reply 577. doi: 10.1212/01.wnl.0000344169.51931.e5. No abstract available. |
| 17724284 | Background | Maarrawi J, Peyron R, Mertens P, Costes N, Magnin M, Sindou M, Laurent B, Garcia-Larrea L. Motor cortex stimulation for pain control induces changes in the endogenous opioid system. Neurology. 2007 Aug 28;69(9):827-34. doi: 10.1212/01.wnl.0000269783.86997.37. |
| 10990547 | Background | Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000 Sep 15;527 Pt 3(Pt 3):633-9. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x. |
| 20633386 | Background | Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Paulus W, Hummel F, Boggio PS, Fregni F, Pascual-Leone A. Transcranial direct current stimulation: State of the art 2008. Brain Stimul. 2008 Jul;1(3):206-23. doi: 10.1016/j.brs.2008.06.004. Epub 2008 Jul 1. |
| 29454976 | Background | O'Brien AT, Deitos A, Trinanes Pego Y, Fregni F, Carrillo-de-la-Pena MT. Defective Endogenous Pain Modulation in Fibromyalgia: A Meta-Analysis of Temporal Summation and Conditioned Pain Modulation Paradigms. J Pain. 2018 Aug;19(8):819-836. doi: 10.1016/j.jpain.2018.01.010. Epub 2018 Feb 15. |
| 26869915 | Background | Peng W, Tang D. Pain Related Cortical Oscillations: Methodological Advances and Potential Applications. Front Comput Neurosci. 2016 Feb 4;10:9. doi: 10.3389/fncom.2016.00009. eCollection 2016. |
| 25599301 | Background | Petersen KK, Arendt-Nielsen L, Simonsen O, Wilder-Smith O, Laursen MB. Presurgical assessment of temporal summation of pain predicts the development of chronic postoperative pain 12 months after total knee replacement. Pain. 2015 Jan;156(1):55-61. doi: 10.1016/j.pain.0000000000000022. |
| 28025007 | Background | Ploner M, Sorg C, Gross J. Brain Rhythms of Pain. Trends Cogn Sci. 2017 Feb;21(2):100-110. doi: 10.1016/j.tics.2016.12.001. Epub 2016 Dec 23. |
| 27045524 | Background | Potvin S, Marchand S. Pain facilitation and pain inhibition during conditioned pain modulation in fibromyalgia and in healthy controls. Pain. 2016 Aug;157(8):1704-1710. doi: 10.1097/j.pain.0000000000000573. |
| 11240089 | Background | Staud R, Vierck CJ, Cannon RL, Mauderli AP, Price DD. Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. Pain. 2001 Mar;91(1-2):165-75. doi: 10.1016/s0304-3959(00)00432-2. |
| 25844555 | Background | Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, Cohen M, Evers S, Finnerup NB, First MB, Giamberardino MA, Kaasa S, Kosek E, Lavand'homme P, Nicholas M, Perrot S, Scholz J, Schug S, Smith BH, Svensson P, Vlaeyen JWS, Wang SJ. A classification of chronic pain for ICD-11. Pain. 2015 Jun;156(6):1003-1007. doi: 10.1097/j.pain.0000000000000160. No abstract available. |
| 26652115 | Background | Woods AJ, Antal A, Bikson M, Boggio PS, Brunoni AR, Celnik P, Cohen LG, Fregni F, Herrmann CS, Kappenman ES, Knotkova H, Liebetanz D, Miniussi C, Miranda PC, Paulus W, Priori A, Reato D, Stagg C, Wenderoth N, Nitsche MA. A technical guide to tDCS, and related non-invasive brain stimulation tools. Clin Neurophysiol. 2016 Feb;127(2):1031-1048. doi: 10.1016/j.clinph.2015.11.012. Epub 2015 Nov 22. |
| 31803005 | Background | Zortea M, Ramalho L, Alves RL, Alves CFDS, Braulio G, Torres ILDS, Fregni F, Caumo W. Transcranial Direct Current Stimulation to Improve the Dysfunction of Descending Pain Modulatory System Related to Opioids in Chronic Non-cancer Pain: An Integrative Review of Neurobiology and Meta-Analysis. Front Neurosci. 2019 Nov 18;13:1218. doi: 10.3389/fnins.2019.01218. eCollection 2019. |
| 41015289 | Derived | Gil-Ugidos A, Alcantara-Espinosa J, Rubal-Otero L, Mayo-Moldes M, Samartin-Veiga N, Carrillo-de-la-Pena MT. Transcranial electrical stimulation (tES) in chronic pain patients: Effects on daily-reported symptoms. Anaesth Crit Care Pain Med. 2026 Jan;45(1):101613. doi: 10.1016/j.accpm.2025.101613. Epub 2025 Sep 25. |
| 40735279 | Derived | Fernandez A, Rubal-Otero L, Gil-Ugidos A, Pinal D, Gonzalez-Villar AJ, Carrillo-de-la-Pena MT. Distinct resting state neural activity in chronic pain patients who respond to transcranial electric stimulation for pain relief. Front Hum Neurosci. 2025 Jul 15;19:1546414. doi: 10.3389/fnhum.2025.1546414. eCollection 2025. |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D007592 | Joint Diseases |
| D001416 | Back Pain |
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D004191 | Behavioral Disciplines and Activities |
| D004597 | Electroshock |
| D011580 | Psychological Techniques |