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

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.

Reduced basal ganglia µ-opioid receptor availability in trigeminal neuropathic pain: a pilot study.

BACKGROUND: Although neuroimaging techniques have provided insights into the function of brain regions involved in Trigeminal Neuropathic Pain (TNP) in humans, there is little understanding of the molecular mechanisms affected during the course of this disorder. Understanding these processes is crucial to determine the systems involved in the development and persistence of TNP. FINDINGS: In this study, we examined the regional µ-opioid receptor (µOR) availability in vivo (non-displaceable binding potential BPND) of TNP patients with positron emission tomography (PET) using the µOR selective radioligand [11C]carfentanil. Four TNP patients and eight gender and age-matched healthy controls were examined with PET. Patients with TNP showed reduced µOR BPND in the left nucleus accumbens (NAc), an area known to be involved in pain modulation and reward/aversive behaviors. In addition, the µOR BPND in the NAc was negatively correlated with the McGill sensory and total pain ratings in the TNP patients. CONCLUSIONS: Our findings give preliminary evidence that the clinical pain in TNP patients can be related to alterations in the endogenous µ-opioid system, rather than only to the peripheral pathology. The decreased availability of µORs found in TNP patients, and its inverse relationship to clinical pain levels, provide insights into the central mechanisms related to this condition. The results also expand our understanding about the impact of chronic pain on the limbic system.