The effects of transcranial direct current stimulation on metabolite changes at the anterior cingulate cortex in neuropathic pain: a pilot study

Abstract

BackgroundNeuropathic pain (NP) in individuals with spinal cord injury (SCI) is both common and highly refractory to treatment. Primary motor cortex stimulation can relieve pain by interrupting the transmission of noxious information of descending pain modulatory systems including the anterior cingulate cortex (ACC). Previous research has shown that transcranial direct current stimulation (tDCS) can produce pain relief in individuals with NP. However, the underlying mechanisms for these effects are not yet understood. Research findings suggest the possibility that changes in brain metabolite concentrations produced by tDCS might explain some of these effects. For example, previous research has shown that SCI-related NP is associated with elevated levels of glutamine combined glutamate (Glx) per creatine (Glx/Cr). In addition, decreased N-acetylaspartate (NAA) has been observed in the ACC in individuals with chronic pain.MethodsWe used magnetic resonance spectroscopy (MRS) to study changes in NAA and Glx levels in the ACC after tDCS treatment. Ten patients with SCI with NP were given five daily anodal tDCS sessions, and an MRS evaluation was performed before and after treatment.ResultsThe results showed treatment-related reductions in pain, and increases in both Glx/Cr and NAA/Cr in the ACC. The observed increase in NAA/Cr is consistent with the possibility that tDCS improves the descending pain modulation system by increasing the neuronal activity in the ACC.ConclusionThe findings suggest the possibility that tDCS’s beneficial effects on neuropathic pain may be due, at least in part, to the changes it produces in Glx/Cr and NAA/Cr levels in the ACC. Additional research with larger samples sizes and a control group to evaluate this possibility is warranted.

Reduced Glutamate in the Medial Prefrontal Cortex Is Associated With Emotional and Cognitive Dysregulation in People With Chronic Pain

“…Given that the mPFC is implicated in emotional appraisal (19–21), cognition (19–22) and extinction of fear (19–21), could a decrease in glutamate be associated with the increased pessimistic thinking, fear and worry symptoms commonly found in people with chronic pain? Indeed spectroscopy studies have revealed that glutamate mediates the behavioral sequelae associated with anxiety and stress (23) as well as the sequelae of pain perception itself (24, 25).…”

Magnetic resonance spectroscopy with transcranial direct current stimulation to explore the underlying biochemical and physiological mechanism of the human brain: A systematic review

“…Nineteen studies (out of 34 studies in total) complied with all 10 ROB criteria while three studies (Rae et al, 2013;Ryan et al, 2018;Siniatchkin et al, 2012) failed to satisfy one criterion, two studies (Auvichayapat et al, 2017;O'Shea et al, 2017) two criteria. Three studies (Barron et al, 2016;Koolschijn et al, 2019;Tremblay et al, 2014) failed to fulfil four criteria, and five studies (Auvichayapat et al, 2018;Clark et al, 2011;Jalali et al, 2018;Zappasodi et al, 2018) failed to fulfil three criteria. Figure 2 shows a traffic light plot and summary plot for ROB analysis generated using an online R-based tool, Robvis (McGuinness and Higgins, 2020).…”

“…The initial literature search retrieved 59 publications from PubMed and 113 publications from Web of Science. The abstracts of all reports were scanned and 34 publications (Antonenko et al, 2017(Antonenko et al, , 2019Auvichayapat et al, 2017Auvichayapat et al, , 2018Bachtiar et al, 2015Bachtiar et al, , 2018 The second tDCS was performed 115 min after the first one.…”

“…In the majority of cases, these were measured in the left M1. Considering that all the studies except one (Tremblay et al, 2014) report GABA decrease and no change in Glx/Gln/Glu in the left M1 after anodal modulation, it is very likely that the LTP-like effect of tDCS are driven by a reduction in the inhibitory tone (Antonenko et al, 2017(Antonenko et al, , 2019Auvichayapat et al, 2018;Bachtiar et al, 2018;Kim et al, 2014;O'Shea et al, 2017;Patel et al, 2019;Stagg et al, 2009;Tremblay et al, 2014). Similarly, the LTD-like effect of the cathodal modulation might be caused by reduced levels of the excitatory neurotransmitter as Glx/Gln/Glu decrease has been reported following cathodal tDCS with a concomitant reduction in GABA (Antonenko et al, 2019;Stagg et al, 2009).…”

Observations of Autonomic Variability Following Central Neuromodulation for Chronic Neuropathic Pain in Spinal Cord Injury

“…These theories are further validated in the context of post‐SCI NP by studies that show these areas as having undergone structural and functional changes in the chronic phase following injury (10, 11). Similarly, others have demonstrated that transcranial direct current stimulation interventions may confer analgesia in persons with SCI and NP by way of modulating descending pain pathways at the level of the ACC (12). Furthermore, elegantly designed studies utilizing functional MRI found these cortical areas within the PNM to demonstrate increased activity specifically in persons with SCI + NP relative to able bodied persons (AB) upon pain induction (4).…”