Immediate effects of tDCS on the μ-opioid system of a chronic pain patient

Marcos Fabio DosSantos, Tiffany M Love, Ilkka Kristian Martikainen, Thiago Dias Nascimento, Felipe Fregni, Chelsea Cummiford, Misty Dawn Deboer, Jon-Kar Zubieta, Alexandre F M Dasilva, Marcos Fabio DosSantos, Tiffany M Love, Ilkka Kristian Martikainen, Thiago Dias Nascimento, Felipe Fregni, Chelsea Cummiford, Misty Dawn Deboer, Jon-Kar Zubieta, Alexandre F M Dasilva

Abstract

We developed a unique protocol where transcranial direct current stimulation (tDCS) of the motor cortex is performed during positron emission tomography (PET) scan using a μ-opioid receptor (μOR) selective radiotracer, [(11)C]carfentanil. This is one of the most important central neuromechanisms associated with pain perception and regulation. We measured μOR non-displaceable binding potential (μOR BP(ND)) in a trigeminal neuropathic pain patient (TNP) without creating artifacts, or posing risks to the patient (e.g., monitoring of resistance). The active session directly improved in 36.2% the threshold for experimental cold pain in the trigeminal allodynic area, mandibular branch, but not the TNP patient's clinical pain. Interestingly, the single active tDCS application considerably decreased μORBP(ND) levels in (sub)cortical pain-matrix structures compared to sham tDCS, especially in the posterior thalamus. Suggesting that the μ-opioidergic effects of a single tDCS session are subclinical at immediate level, and repetitive sessions are necessary to revert ingrained neuroplastic changes related to the chronic pain. To our knowledge, we provide data for the first time in vivo that there is possibly an instant increase of endogenous μ-opioid release during acute motor cortex neuromodulation with tDCS.

Keywords: PET; neuroplasticity; opioid receptors; post-herpetic neuralgia; tDCS; trigeminal neuropathic pain.

Figures

Figure 1
Figure 1
Decrease in μ-opioid receptor binding associated with transcranial direct current stimulation. Upper panel: μOR BPND during the baseline PET. Lower panel: μOR BPND during active tDCS. ACC, anterior cingulate cortex; NAc, nucleus accumbens; Ins, insula.
Figure 2
Figure 2
(A) Decreased thalamic μ-opioid receptor availability during active tDCS, represented in the coronal plane. (B) Bar chart illustrating the μ-opioid receptor binding potential in the right and left thalamus during the late phase of the first and second PET scans.

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