Neural correlates of the antinociceptive effects of repetitive transcranial magnetic stimulation on central pain after stroke

Abstract

Background: Repetitive transcranial magnetic stimulation (rTMS) modulates central neuropathic pain in some patients after stroke, but the mechanisms of action are uncertain.

Objective: . The authors used diffusion tensor imaging (DTI) and functional MRI (fMRI) to evaluate the integrity of the thalamocortical tract (TCT) and the activation pattern of the pain network in 22 patients with poststroke central pain.

Methods: Each patient underwent daily 10-Hz rTMS sessions for 1000 pulses on 5 consecutive days over the hotspot for the first dorsal interosseus muscle. Pain severity was monitored using the Visual Analogue Scale (VAS). Mood was assessed by the Hamilton Depression Rating Scale.

Results: Clinical data from all participants along with the DTI and fMRI findings from 10 patients were analyzed. VAS scores decreased significantly, if modestly, following administration of rTMS in 14 responders, which lasted for 2 weeks after the intervention. Regression analysis showed a significant correlation between less initial depression and higher antalgic effect of rTMS. Integrity of the superior TCT in the ipsilesional hemisphere showed significant correlation with change of VAS score after rTMS. fMRI showed significantly decreased activity in the secondary somatosensory cortex, insula, prefrontal cortex, and putamen in rTMS responders, whereas no change was noted in nonresponders.

Conclusion: . Mood may affect the modest antinociceptive effects of rTMS that we found, which may be mediated by the superior TCT through modulation of a distributed pain network.

Conflict of interest statement

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1

Experimental design: all patients received 5 daily sessions of 10 Hz rTMS (1000 pulses) over the M1 of the affected hemisphere. Severity of pain was assessed using the VAS scores before, immediately after, and 2 weeks after rTMS; sensory function and depression scores were also assessed before and immediately after rTMS in all patients; 10 patients underwent functional imaging studies before and after rTMS. Abbreviations: rTMS, repetitive transcranial magnetic stimulation; fMRI, functional MRI; DTI, diffusion tensor imaging; F/U, follow up; VAS, Visual Analogue Scale.

Figure 2

(A) Individual TCTs: the superior TCT (green in the right hemisphere and red in the left hemisphere) and anterior TCT (blue in the right hemisphere and purple in the left hemisphere) of the responder group are displayed on the left-hand side and those of the nonresponder group are displayed on the right-hand side. The superior TCTs of the responder group are well preserved, whereas those of the nonresponder group show extreme deterioration in the stroke hemisphere. Normal TCTs of 1 healthy person (58-year-old, female) who did not have a past history of previous stroke or other neurological disease are shown on the bottom of the right-hand side. Arrows indicate the lesion sides. (B, C) Correlation between integrity of the superior TCT and pain reponse to rTMS. B. VAS change correlated with ADC of the superior TCT (R2= 0.60, P < .01). (C) VAS change correlated with the delineation ratio of the volume of the bilateral superior TCT (defined as the ratio of the volume of the superior TCT in the affected hemisphere to that of the unaffected hemisphere; R2= 0.60, P < .01). Abbreviations: TCT, thalamocortical tract; rTMS, repetitive transcranial magnetic stimulation; VAS, Visual Analogue Scale; ADC, apparent diffusion coefficient.

Figure 3

Brain areas activated by noxious tactile stimulation in the responder group (A) and the nonresponder group (B). fMRI results showed activation before rTMS on the left side (A-1, B-1), and activation after rTMS in the middle (A-2, B-2) are shown in yellow/red color. fMRI on the right side (A-3, B-3) showed decreased activation after rTMS (cyan/blue color, before/after rTMS). (C) The clinical-anatomic-functional relationship revealed in this study. Abbreviations: M1, primary motor cortex; SI, primary sensory cortex; SII, secondary sensory cortex; Sf, superior frontal gyrus; Mf, middle frontal gyrus; If, inferior frontal gyrus; Is, insula; Pu, putamen; Cbll, cerebellum; fMRI, functional MRI; rTMS, repetitive transcranial magnetic stimulation.