1. Cerebellar Direct Current Stimulation (ctDCS) for the treatment of phantom limb pain
Bocci Tommaso 1,2, De Carolis G.3, Mansani F.1, De Rosa A.1, Ferrucci R. 2, Priori A. 2, Valeriani M. 4, Sartucci F.1,5
1 Department of Health Sciences, University of Milan, Milan, Italy; 2 Department of Clinical and Experimental Medicine, University of Pisa; 3 Pain Therapy Unit, University of Pisa, Pisa, Italy; 4 Division of Neurology, Ospedale Bambino Gesù, Rome, Italy; 5 Neuroscience Institute, National Research Council, Pisa, Italy 1 1

2. From bench to bedside: putative pathways
What did we learn from MRI studies?
Moulton et al., Brain Res Rev 2010
Borsook et al., Cerebellum 2008; Dimitrova et al., J Neurophysiol 2003;
Plogahus, Science 1999

3. A new target for pain treatment in humans: the cerebellum
Parazzini et al., Clin Neurophysiol 2013
Bocci et al., Restor Neurol Neurosci 2015
Bocci et al., Cerebellum 2016

4. Supra-spinal mechanisms:
Central sensitization and chronic pain syndromes: the “red flags” for putative therapies
Supra-spinal mechanisms:
Reorganization of sensorimotor maps
Thalamocortical Dysrhythmia
Spinal mechanisms:
Phenotipic switch in the expression of neuropeptides
here was significant reduction in functional
connectivity from the ACCs to the limbic areas (the parahippocampal gyrus and the posterior cingulate cortex), pain-processing area
(the insula), and visuospatial areas (the cuneus). Moreover, the degree of reduction in functional connectivity for the ACC to the
amygdala and the precuneus was linearly correlated with the severity of intraepidermal nerve fiber depletion.
Hsieh et al., Pain 2015
Suzuki&Dickenson, Neurosignals 2006

5. tDCS and phantom limb pain (PLP)
Is it really effective?
tDCS over the primary motor cortex (Bolognini et al., J Pain 2015)

6. Experimental Protocol
1. Clinical Scales
2. LEPs
(nociceptive threshold, N1 and N2/P2 amplitude/latency)
3. fMRI
1. Clinical Scales
2. LEPs
(nociceptive threshold, N1 and N2/P2 amplitude/latency)
3. fMRI
1. Clinical Scales
2. LEPs
(nociceptive threshold, N1 and N2/P2 amplitude/latency)
3. fMRI T0 T1
(immediately after ctDCS)
T2 and T3
(after two and three weeks ctDCS completion)
Cerebellar tDCS (sham or anodal), five days a week (2.0 mA, 20’ per day).

7. Clinical scores
Bocci et al., Cerebellum 2019

8. Neurophysiological outcome
Bocci et al., Cerebellum 2019

9. Conclusions
Anodal stimulation significantly improves both painful and non painful phantom limb sensations, dampening LEP amplitudes over time;
Cerebellar polarization may be useful for the treatment of pain syndromes; it may act not only on spinal nociceptive neurons, but also on wide-range cortical networks of the pain matrix, thus influencing pain experience through top-down and bottom-up mechanisms.