Non-invasive Motor Cortex Neuromodulation Reduces Secondary Hyperalgesia and Enhances Activation of the Descending Pain Modulatory Network.

Timothy J Meeker,Joel D Greenspan,Michael L Keaser,Shariq A Khan,David A Seminowicz,Rao P Gullapalli

doi:10.3389/fnins.2019.00467

Timothy J Meeker, Joel D Greenspan + Show 4 more

Open Access

https://doi.org/10.3389/fnins.2019.00467

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Abstract

Central sensitization is a driving mechanism in many chronic pain patients, and manifests as hyperalgesia and allodynia beyond any apparent injury. Recent studies have demonstrated analgesic effects of motor cortex (M1) stimulation in several chronic pain disorders, yet its neural mechanisms remain uncertain. We evaluated whether anodal M1 transcranial direct current stimulation (tDCS) would mitigate central sensitization as measured by indices of secondary hyperalgesia. We used a capsaicin-heat pain model to elicit secondary mechanical hyperalgesia in 27 healthy subjects. In an assessor and subject-blind randomized, sham-controlled, crossover trial, anodal M1 tDCS decreased the intensity of pinprick hyperalgesia more than cathodal or sham tDCS. To elucidate the mechanism driving analgesia, subjects underwent fMRI of painful mechanical stimuli prior to and following induction of the pain model, after receiving M1 tDCS. We hypothesized that anodal M1 tDCS would enhance engagement of a descending pain modulatory (DPM) network in response to mechanical stimuli. Anodal tDCS normalized the effects of central sensitization on neurophysiological responses to mechanical pain in the medial prefrontal cortex, pregenual anterior cingulate cortex, and periaqueductal gray, important regions in the DPM network. Taken together, these results provide support for the hypothesis that anodal M1-tDCS reduces central sensitization-induced hyperalgesia through the DPM network in humans.

Highlights

Moderate to severe chronic pain afflicts 17–33% of adults in western countries (Bouhassira et al, 2008; Von Korff et al, 2016)
This study presented many differences compared to our planned study including method of capsaicin application, primary outcome of thermal allodynia, and mode of motor cortex stimulation, we determined that we would need data from 25 subjects to achieve a similar effect size as the Tamura et al (2004) study with a power of 0.8 and an alpha of 0.95
To establish that pain intensity ratings taken at 15 min after removal of the capsaicin-heat pain (C-HP) did not differ among intervention types, we used an linear mixed models (LMM) including intervention type and probe force (128, 256, and 512 mN) and found no significant intervention main effect (F-stat = 2.08; p = 0.13)

Summary

Introduction

Moderate to severe chronic pain afflicts 17–33% of adults in western countries (Bouhassira et al, 2008; Von Korff et al, 2016). All successful M1 tDCS trials in chronic pain patients have favored anodal tDCS or high frequency rTMS, both methods that favor increasing excitability of the cortex, while cathodal tDCS has only occasionally demonstrated analgesic effects in assays of phasic acute pain (Mylius et al, 2012; Vaseghi et al, 2014, 2015). This led us to evaluate the efficacy of M1 tDCS on symptoms evoked by the capsaicin-heat pain (C-HP) model (Anderson et al, 2002; Furman et al, 2018). We expected initial effects of pain alleviation after one 20 min session, since motor cortex excitability, measured by motor-evoked potentials, is altered after 5 min of M1 tDCS (Nitsche and Paulus, 2000)

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