Paired Acute Invasive/Non-invasive Stimulation (PAINS) study: A phase I/II randomized, sham-controlled crossover trial in chronic neuropathic pain

Tariq Parker; Ashley Raghu; Yongzhi Huang; Martin J Gillies; James J FitzGerald; Tipu Aziz; Alexander L Green

doi:10.1016/j.brs.2021.10.384

Paired Acute Invasive/Non-invasive Stimulation (PAINS) study: A phase I/II randomized, sham-controlled crossover trial in chronic neuropathic pain

Brain Stimul. 2021 Nov-Dec;14(6):1576-1585. doi: 10.1016/j.brs.2021.10.384. Epub 2021 Oct 19.

Authors

Tariq Parker¹, Ashley Raghu², Yongzhi Huang³, Martin J Gillies², James J FitzGerald², Tipu Aziz², Alexander L Green²

Affiliations

¹ Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom; Neurosurgery Department, Massachusetts General Hospital, Boston, MA, USA. Electronic address: tparker3@mgh.harvard.edu.
² Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
³ Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom; Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China.

PMID: 34673258
DOI: 10.1016/j.brs.2021.10.384

Abstract

Background: Dorsal root ganglion (DRG) stimulation, an invasive method of neuromodulation, and transcranial direct current stimulation (tDCS), a non-invasive method of altering cortical excitability, have both proven effective in relieving chronic pain.

Objective: We employed a randomized, sham-controlled crossover study design to investigate whether single-session tDCS would have an additive therapeutic effect alongside DRG stimulation (DRGS) in the treatment of chronic pain.

Methods: Sixteen neuropathic pain patients who were previously implanted with DRG stimulators were recruited. Baseline pain scores were established with DRGS-OFF. Pain scores were then recorded with DRGS-ON, after paired sham tDCS stimulation, and after paired active anodal tDCS (a-tDCS) stimulation. For active tDCS, patients were randomized to 'MEG (magnetoencephalography) localized' tDCS or contralateral motor cortex (M1) tDCS for 30 min. EEG recordings and evaluations of tDCS adverse effects were also collected.

Results: All participants reported the interventions to be tolerable with no significant adverse effects during the session. Paired DRGS/active tDCS resulted in a significant reduction in pain scores compared to paired DRGS-ON/sham tDCS or DRGS alone. There was no difference in the additive effect of M1 vs. MEG-localized tDCS. Significant augmentation of beta activity was observed between DRGS-OFF and DRGS-ON conditions, as well as between paired DRGS-ON/sham tDCS and paired DRGS-ON/active tDCS.

Conclusion: Our results indicate that a single session of tDCS alongside DRGS is safe and can significantly reduce pain acutely in neuropathic pain patients. Paired invasive/non-invasive neuromodulation is a promising new treatment strategy for pain management and should be evaluated further to assess long-term benefits.

Keywords: Chronic pain; Dorsal root ganglion stimulation; EEG; Transcranial direct current stimulation.

Publication types

Clinical Trial, Phase I
Clinical Trial, Phase II
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Chronic Pain* / therapy
Cross-Over Studies
Humans
Neuralgia* / therapy
Pain Management / methods
Transcranial Direct Current Stimulation* / methods
Transcranial Magnetic Stimulation / methods