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Modulating pain in CRPS with tDCS Giridhar Gundu, M.D. PGY III Dept. of PM&R University of Kentucky 5/22/2012.

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Presentation on theme: "Modulating pain in CRPS with tDCS Giridhar Gundu, M.D. PGY III Dept. of PM&R University of Kentucky 5/22/2012."— Presentation transcript:

1 Modulating pain in CRPS with tDCS Giridhar Gundu, M.D. PGY III Dept. of PM&R University of Kentucky 5/22/2012

2 Complex regional pain syndrome O CRPS is a highly painful, limb-confined condition, which arises usually after trauma. O Associated with a particularly poor quality of life, and large health-care and societal costs. O Crossroads of interests of several disciplines including rheumatology, pain medicine, neurology, physiatry.

3 Clinical presentation of CRPS Early CRPS of the right hand: Clearly visible signs include swelling, red color and a shiny skin. As the disease progresses some of these visible signs can partially or completely disappear while pain may persist unabated.

4 Patients with CRPS can present in many different ways……. O Limbs can be hot or cold, shiny, swollen or thin, red or blue with scaling or clammy skin. O Some patients cannot tolerate slight air movement on their skin, while others have completely lost the ability to feel any stimulus to the limb (with normal nerve conduction studies). O Blister formation, skin ulcerations, severe atrophy, joint ankylosis, dystonia and myoclonus may also be present. O Joints usually feel stiff with reduced range and weakness; often limb parts cannot be moved at all, and there is a fine tremor.


6 Causes of CRPS UNKNOWN???????

7 There are currently eight major concepts about CRPS etiology. 1. Inflammatory process 2. Sympathetically mediated disorder 3. Autoimmune condition 4. Limb ischemia/ischemia reperfusion injury 5. Cortical reorganization 6. Nerve damage 7. Neurogenic inflammation 8. Alternative concepts

8 O The IASP has proposed dividing CRPS into two types based on the presence of nerve lesion following the injury: O CRPS type I (reflex sympathetic dystrophy). Minor injuries or fracture of a limb precede the onset of symptoms. O CRPS type II (causalgia) develops after injury to a major peripheral nerve.

9 O CRPS diagnosis is based upon clinical criteria and that there is so far no gold standard nor any objective diagnostic tool. O It is a diagnosis of exclusion. O Budapest Criteria used for diagnosis

10 4. No other diagnosis can better explain the signs and symptoms.

11 Diagnostic tests which may aid the diagnosis of CRPS O X-ray O 3-phase bone scan O Quantitative sensory testing (QST) O Autonomic testing O Thermography

12 PAIN Burning coldness Crushing, Numb and hot Help me someone, Make it stop! It started out so innocently When I fell off my bike My foot began with a twinge Then relentlessly, Crept up my limb It became unbearable Moments passed like years Looking for a miracle A never-ending nightmare Guillotines, power saws Alligators and lion's jaws Nightmares of horror Terrified to close my eyes Fearing more awaits inside Branded by the endless pain Am I going to go insane? You don't know just how I feel Does that mean it isn't real? Is my world just not true? Don't I see and feel -- like you? Please don't stop trying I can't help my crying I feel so maimed Help me, Help me I'm in pain!

13 Treatment

14 O Pharmacological (Gabapentin, corticosteroids,antidepressants, anticonvulsants, opioids capsaicin, lidocaine, clonazepam, ketamine, bisphosphonates) O Interventional O Neurostimulatory O Psychological/CBT O Physical and vocational rehabilitation O Patient education There is a desperate need for further research into the treatment of CRPS

15 Transcranial direct current stimulation (tDCS) O Uses weak electrical currents (1-2mA) to modulate the activity of neurons in the brain O In tDCS, the anodal electrode placed over the cortical target results in increased cortical excitability, whereas cathodal stimulation decreases local cortical excitability.

16 O The primary action of tDCS for pain reduction is direct modulation of activity in certain areas of the brain that are involved in pain processing, such as the thalamus and inhibitory corticospinal mechanisms. O tDCS is used in other pain syndromes, such as fibromyalgia, phantom pain and central pain in traumatic spinal cord injury.

17 Objectives Our proposed study has 2 specific aims: Determine the effect of tDCS on pain and quality of life associated with CRPS. Determine the specificity of tDCS site for modulation of pain and quality of life associated with CRPS.

18 Study Design O Double-blind, randomized, placebo-controlled study O Subjects stratified based on pain intensity and duration of CRPS. O Subjects then randomly assigned to 1 of the following 3 groups: Group 1: anodal tDCS over DLPFC Group 2: anodal tDCS over M1 Group 3: sham tDCS over DLPFC

19 4 evaluation sessions and 10 treatment sessions with each subject T0T1T3Begin treatment 1 week T4

20 Study Population Inclusion criteria: Subjects must be at least 18 years of age with diagnosed CRPS following the recently updated Budapest criteria Exclusion criteria: Within 1 month of recruitment, addition or change in the dosage of drugs known to interfere with pain Untreated depression History of head injury with loss of consciousness, severe alcohol or drug abuse, or psychiatric illness, Seizure disorder Pregnancy Presence of ferromagnetic material in the cranium except in the mouth, including metal fragments from occupational exposure, and surgical clips in or near the brain.

21 Intervention One 35 cm 2 saline-soaked sponge electrodes placed over the scalp sites overlying the relevant cortex and reference electrode placed supraorbitally. Battery-operated direct current stimulator for delivery of stimulation (Magstim Ltd., Wales, UK). With the exception of the control group, each subject will receive 20 minutes of tDCS at an intensity of 1.4mA. (These values result in a current density of 0.04mA/cm 2 and a charge density of 480 Coulombs/M 2 ) For the control condition, stimulation intensity will be ramped up then ramped down over a 30-second window.

22 Assessment O Short-Form McGill Pain Questionnaire, which will serve as the primary behavioral outcome for this study. O The SF-36 Health Survey will be used to measure changes in quality of life.

23 References O de Mos M, Huygen FJ, van der Hoeven-Borgman M, Dieleman JP, Ch Stricker BH, Sturkenboom MC. Outcome of the complex regional pain syndrome. Clin J Pain. 2009;25:590-597 O Perez RS, Kwakkel G, Zuurmond WW, de Lange JJ. Treatment of reflex sympathetic dystrophy (crps type 1): A research synthesis of 21 randomized clinical trials. J Pain Symptom Manage. 2001;21:511-526 O Picarelli H, Teixeira MJ, de Andrade DC, Myczkowski ML, Luvisotto TB, Yeng LT, Fonoff ET, Pridmore S, Marcolin MA. Repetitive transcranial magnetic stimulation is efficacious as an add-on to pharmacological therapy in complex regional pain syndrome (crps) type i. J Pain. 2010;11:1203-1210 O Pleger B, Janssen F, Schwenkreis P, Volker B, Maier C, Tegenthoff M. Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type i. Neurosci Lett. 2004;356:87-90 O Goebel A. Complex regional pain syndrome in adults. Rheumatology (Oxford). 2011;50:1739-1750 O Maihofner C, Handwerker HO, Birklein F. Functional imaging of allodynia in complex regional pain syndrome. Neurology. 2006;66:711-717 O Grachev ID, Thomas PS, Ramachandran TS. Decreased levels of n-acetylaspartate in dorsolateral prefrontal cortex in a case of intractable severe sympathetically mediated chronic pain (complex regional pain syndrome, type i). Brain Cogn. 2002;49:102-113 O Seminowicz DA, Wideman TH, Naso L, Hatami-Khoroushahi Z, Fallatah S, Ware MA, Jarzem P, Bushnell MC, Shir Y, Ouellet JA, Stone LS. Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function. J Neurosci. 2011;31:7540- 7550

24 References O Priori A, Berardelli A, Inghilleri M, Pedace F, Giovannelli M, Manfredi M. Electrical stimulation over muscle tendons in humans. Evidence favouring presynaptic inhibition of ia fibres due to the activation of group iii tendon afferents. Brain. 1998;121 ( Pt 2):373-380 O Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000;527 Pt 3:633-639 O Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, Cohen LG. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain. 2005;128:490-499 O Fregni F, Boggio PS, Lima MC, Ferreira MJ, Wagner T, Rigonatti SP, Castro AW, Souza DR, Riberto M, Freedman SD, Nitsche MA, Pascual-Leone A. A sham-controlled, phase ii trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain. 2006;122:197-209 O Paulus W. Transcranial direct current stimulation (tdcs). Suppl Clin Neurophysiol. 2003;56:249-254 O 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;1:206-223 O Fregni F, Gimenes R, Valle AC, Ferreira MJ, Rocha RR, Natalle L, Bravo R, Rigonatti SP, Freedman SD, Nitsche MA, Pascual-Leone A, Boggio PS. A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Arthritis Rheum. 2006;54:3988-3998 O Roizenblatt S, Fregni F, Gimenez R, Wetzel T, Rigonatti SP, Tufik S, Boggio PS, Valle AC. Site-specific effects of transcranial direct current stimulation on sleep and pain in fibromyalgia: A randomized, sham-controlled study. Pain Pract. 2007;7:297-306

25 References O Boggio PS, Zaghi S, Fregni F. Modulation of emotions associated with images of human pain using anodal transcranial direct current stimulation (tdcs). Neuropsychologia. 2009;47:212-217 O Fenton BW, Palmieri PA, Boggio P, Fanning J, Fregni F. A preliminary study of transcranial direct current stimulation for the treatment of refractory chronic pelvic pain. Brain Stimul. 2009;2:103-107 O Antal A, Terney D, Kuhnl S, Paulus W. Anodal transcranial direct current stimulation of the motor cortex ameliorates chronic pain and reduces short intracortical inhibition. J Pain Symptom Manage. 2010;39:890-903 O Mori F, Codeca C, Kusayanagi H, Monteleone F, Buttari F, Fiore S, Bernardi G, Koch G, Centonze D. Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis. J Pain. 2010;11:436- 442 O Harden RN, Bruehl S, Perez RS, Birklein F, Marinus J, Maihofner C, Lubenow T, Buvanendran A, Mackey S, Graciosa J, Mogilevski M, Ramsden C, Chont M, Vatine JJ. Validation of proposed diagnostic criteria (the "Budapest criteria") for complex regional pain syndrome. Pain.150:268-274 O Bikson M, Datta A, Elwassif M. Establishing safety limits for transcranial direct current stimulation. Clin Neurophysiol. 2009;120:1033-1034 O Gandiga PC, Hummel FC, Cohen LG. Transcranial dc stimulation (tdcs): A tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol. 2006;117:845-850 O Poreisz C, Boros K, Antal A, Paulus W. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull. 2007;72:208-214 O Nitsche MA, Liebetanz D, Lang N, Antal A, Tergau F, Paulus W. Safety criteria for transcranial direct current stimulation (tdcs) in humans. Clin Neurophysiol. 2003;114:2220-2222; author reply 2222-2223

26 References O Nitsche MA, Boggio PS, Fregni F, Pascual-Leone A. Treatment of depression with transcranial direct current stimulation (tdcs): A review. Exp Neurol. 2009;219:14-19 O Edwards DJ, Krebs HI, Rykman A, Zipse J, Thickbroom GW, Mastaglia FL, Pascual-Leone A, Volpe BT. Raised corticomotor excitability of m1 forearm area following anodal tdcs is sustained during robotic wrist therapy in chronic stroke. Restor Neurol Neurosci. 2009;27:199-207 O Boggio PS, Nunes A, Rigonatti SP, Nitsche MA, Pascual-Leone A, Fregni F. Repeated sessions of noninvasive brain dc stimulation is associated with motor function improvement in stroke patients. Restor Neurol Neurosci. 2007;25:123-129 O Hummel FC, Voller B, Celnik P, Floel A, Giraux P, Gerloff C, Cohen LG. Effects of brain polarization on reaction times and pinch force in chronic stroke. BMC Neurosci. 2006;7:73

27 Thank you

28 Questions?

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