1. Modulating pain in CRPS with tDCS Giridhar Gundu, M.D. PGY IV Co-investigator: Kenneth Chelette, M.S. Dept. of PM&R University of Kentucky 5/23/2013

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.

5. Causes of CRPS UNKNOWN???????

6. 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

7. 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.

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

9. Treatment

10. 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

11. 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.

12. 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.

13. 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.

14. 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

15. 4 evaluation sessions and 10 treatment sessions with each subject T0T1T3Begin treatment 1 week T4

16. 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.

17. 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.

18. 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.

19. O We have secured approval by the University of Kentucky Institutional Review Board and begun enrollment of subjects. O Three subjects with chronic CRPS were enrolled after informed consent (projected total enrollment: n=30). O Each subject was randomly assigned to 1 of 3 groups: 1) anodal stimulation over left dorsolateral prefrontal cortex, 2) anodal stimulation over left primary motor cortex, or 3) sham.

20. O We delivered tDCS daily for 10 consecutive weekdays. O Assessments of pain and quality of life including the Short- Form McGill Pain Questionnaire and The SF-36 Health Survey were performed by a blinded evaluator at four time points: O 1-week prior to start of intervention, immediately prior to start of intervention, after intervention day 5, and after intervention day 10

21. Results ?

23. Thank you

24. Questions?