Dopamine D2/D3 imbalance during migraine attack and allodynia in vivo.

OBJECTIVE: To evaluate in vivo the dynamics of endogenous dopamine (DA) neurotransmission during migraine ictus with allodynia. METHODS: We examined 8 episodic migraineurs and 8 healthy controls (HC) using PET with [11C]raclopride. The uptake measure of [11C]raclopride, nondisplaceable binding potential (BPND), would increase when there was a reduction in endogenous DA release. The opposite is true for a decrease in [11C]raclopride BPND. Patients were scanned twice: one PET session was during a spontaneous migraine ictus at rest, followed by a sustained thermal pain threshold (STPT) challenge on the trigeminal region, eliciting an allodynia experience; another was during interictal phase. RESULTS: Striatal BPND of [11C]raclopride in migraineurs did not differ from HC. We found a significant increase in [11C]raclopride BPND in the striatum region of migraineurs during both headache attack and allodynia relative to interictal phase. However, when compared to the migraine attack at rest, migraineurs during the STPT challenge had a significant sudden reduction in [11C]raclopride BPND in the insula. Such directional change was also observed in the caudate of HC relative to the interictal phase during challenge. Furthermore, ictal changes in [11C]raclopride BPND in migraineurs at rest were positively correlated with the chronicity of migraine attacks, and negatively correlated with the frequency during challenge. CONCLUSIONS: Our findings demonstrate that there is an imbalanced uptake of [11C]raclopride during the headache attack and ictal allodynia, which indicates reduction and fluctuation in ictal endogenous DA release in migraineurs. Moreover, the longer the history and recurrence of migraine attacks, the lower the ictal endogenous DA release.

Feasibility of Non-invasive Brain Modulation for Management of Pain Related to Chemoradiotherapy in Patients with Advanced Head and Neck Cancer.

Patients with head and neck cancer often experience a significant decrease in their quality of life during chemoradiotherapy (CRT) due to treatment-related pain, which is frequently classified as severe. Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. In this pilot study, we investigated the clinical impact and central mechanisms of twenty primary motor cortex (M1) stimulation sessions with tDCS during 7 weeks of CRT for head and neck cancer. From 48 patients screened, seven met the inclusion criteria and were enrolled. Electroencephalography (EEG) data were recorded before and after tDCS stimulation as well as across the trial to monitor short and long-term impact on brain function. The compliance rate during the long trial was extremely high (98.4%), and patients mostly reported mild side effects in line with the literature (e.g., tingling). Compared to a large standard of care study from our institution, our initial results indicate that M1-tDCS stimulation has a pain relief effect during the CRT that resulted in a significant attenuation of weight reduction and dysphagia normally observed in these patients. These results translated to our patient cohort not needing feeding tubes or IV fluids. Power spectra analysis of EEG data indicated significant changes in α, ß, and γ bands immediately after tDCS stimulation and, in addition, α, δ, and θ bands over the long term in the seventh stimulation week (p < 0.05). The independent component EEG clustering analysis showed estimated functional brain regions including precuneus and superior frontal gyrus (SFG) in the seventh week of tDCS stimulation. These areas colocalize with our previous positron emission tomography (PET) study where there was activation in the endogenous µ-opioid system during M1-tDCS. This study provides preliminary evidence demonstrating the feasibility and safety of M1-tDCS as a potential adjuvant neuromechanism-driven analgesic therapy for head and neck cancer patients receiving CRT, inducing immediate and long-term changes in the cortical activity and clinical measures, with minimal side-effects.

Outcomes of a Character Strengths-Based Intervention on Self-Esteem and Self-Efficacy of Psychiatrically Hospitalized Youths.

OBJECTIVE: Mental health treatment approaches based on character strengths can be used to complement the traditional focus on functional impairment. The study tested use of a character strengths-based intervention to enhance the self-esteem and self-efficacy of psychiatrically hospitalized youths. METHODS: Eighty-one hospitalized adolescents were randomly assigned to intervention or comparison groups. The intervention used the Values in Action Inventory of Strengths for Youth to discover character strengths and incorporate them into coping skills. Self-efficacy and self-esteem were measured at baseline, postintervention, two weeks, and three months. RESULTS: Self-esteem and self-efficacy initially increased in both groups, but only the intervention group showed sustained improvement. The intervention was associated with increased self-efficacy at two weeks and increased self-efficacy and self-esteem at three months. CONCLUSIONS: A brief, easily administered character strengths-based intervention may be an adjunctive tool in the treatment of psychiatrically hospitalized youths.

Potential Mechanisms Supporting the Value of Motor Cortex Stimulation to Treat Chronic Pain Syndromes.

Throughout the first years of the twenty-first century, neurotechnologies such as motor cortex stimulation (MCS), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS) have attracted scientific attention and been considered as potential tools to centrally modulate chronic pain, especially for those conditions more difficult to manage and refractory to all types of available pharmacological therapies. Interestingly, although the role of the motor cortex in pain has not been fully clarified, it is one of the cortical areas most commonly targeted by invasive and non-invasive neuromodulation technologies. Recent studies have provided significant advances concerning the establishment of the clinical effectiveness of primary MCS to treat different chronic pain syndromes. Concurrently, the neuromechanisms related to each method of primary motor cortex (M1) modulation have been unveiled. In this respect, the most consistent scientific evidence originates from MCS studies, which indicate the activation of top-down controls driven by M1 stimulation. This concept has also been applied to explain M1-TMS mechanisms. Nevertheless, activation of remote areas in the brain, including cortical and subcortical structures, has been reported with both invasive and non-invasive methods and the participation of major neurotransmitters (e.g., glutamate, GABA, and serotonin) as well as the release of endogenous opioids has been demonstrated. In this critical review, the putative mechanisms underlying the use of MCS to provide relief from chronic migraine and other types of chronic pain are discussed. Emphasis is placed on the most recent scientific evidence obtained from chronic pain research studies involving MCS and non-invasive neuromodulation methods (e.g., tDCS and TMS), which are analyzed comparatively.

State-of-art neuroanatomical target analysis of high-definition and conventional tDCS montages used for migraine and pain control.

Although transcranial direct current stimulation (tDCS) studies promise to modulate cortical regions associated with pain, the electric current produced usually spreads beyond the area of the electrodes' placement. Using a forward-model analysis, this study compared the neuroanatomic location and strength of the predicted electric current peaks, at cortical and subcortical levels, induced by conventional and High-Definition-tDCS (HD-tDCS) montages developed for migraine and other chronic pain disorders. The electrodes were positioned in accordance with the 10-20 or 10-10 electroencephalogram (EEG) landmarks: motor cortex-supraorbital (M1-SO, anode and cathode over C3 and Fp2, respectively), dorsolateral prefrontal cortex (PFC) bilateral (DLPFC, anode over F3, cathode over F4), vertex-occipital cortex (anode over Cz and cathode over Oz), HD-tDCS 4 × 1 (one anode on C3, and four cathodes over Cz, F3, T7, and P3) and HD-tDCS 2 × 2 (two anodes over C3/C5 and two cathodes over FC3/FC5). M1-SO produced a large current flow in the PFC. Peaks of current flow also occurred in deeper brain structures, such as the cingulate cortex, insula, thalamus and brainstem. The same structures received significant amount of current with Cz-Oz and DLPFC tDCS. However, there were differences in the current flow to outer cortical regions. The visual cortex, cingulate and thalamus received the majority of the current flow with the Cz-Oz, while the anterior parts of the superior and middle frontal gyri displayed an intense amount of current with DLPFC montage. HD-tDCS montages enhanced the focality, producing peaks of current in subcortical areas at negligible levels. This study provides novel information regarding the neuroanatomical distribution and strength of the electric current using several tDCS montages applied for migraine and pain control. Such information may help clinicians and researchers in deciding the most appropriate tDCS montage to treat each pain disorder.