BackgroundThe non-invasive biomarkers of migraine can help to develop the personalized medication of this disorder. In testing of the antimigraine drugs the capsaicin-induced skin redness with activated TRPV1 receptors in sensory neurons associated with the release of the migraine mediator CGRP has already been widely used.MethodsFourteen migraine patients (mean age 34.6 ± 10.2 years) and 14 healthy volunteers (mean age 29.9 ± 9.7 years) participated in the experiment. A new arrangement of imaging photoplethysmography recently developed by us was used here to discover novel sensitive parameters of dermal blood flow during capsaicin applications in migraine patients.ResultsBlood pulsation amplitude (BPA) observed as optical-intensity waveform varying synchronously with heartbeat was used for detailed exploration of microcirculatory perfusion induced by capsicum patch application. The BPA signals, once having appeared after certain latent period, were progressively rising until being saturated. Capsaicin-induced high BPA areas were distributed unevenly under the patch, forming “hot spots.” Interestingly the hot spots were much more variable in migraine patients than in the control group. In contrast to BPA, a slow component of waveforms related to the skin redness changed significantly less than BPA highlighting the latter parameter as the potential sensitive biomarker of capsaicin-induced activation of the blood flow. Thus, in migraine patients, there is a non-uniform (both in space and in time) reaction to capsaicin, resulting in highly variable openings of skin capillaries.ConclusionBPA dynamics measured by imaging photoplethysmography could serve as a novel sensitive non-invasive biomarker of migraine-associated changes in microcirculation.
Objectives: Immune responses in migraine are poorly characterized, yet implicated in the disease pathogenesis. This study was carried out to characterize purinergic profiles of T-cells in patients with episodic migraine without aura (MWoA) to provide mechanistic evidence for ATP and adenosine involvement in modulation of immune regulation in migraine.Methods: Peripheral blood samples were obtained from patients with migraine (n = 16) and age-matched control subjects (n = 21). Subsets of T-cells were identified by flow cytometry based on specific membrane markers.Results: Migraine patients showed reduced total T-cell counts in the peripheral blood. Whereas the total number of CD3+CD4+, CD3+CD8+, or regulatory T lymphocytes (Treg) was not changed, the proportion of Treg CD45R0+CD62L– and CD45R0–CD62L– cells was increased. Interestingly, in migraine, less Treg cells expressed CD39 and CD73 suggesting disrupted ATP breakdown to adenosine. The negative correlations were observed between the duration of migraine and the relative number of CD73+CD39– Tregs and total number of CD73-positive CD45R0+CD62L+ Tregs.Conclusion: Obtained data indicate that T-cell populations are altered in episodic migraine and suggest the involvement of Tregs in the pathophysiology of this disorder. Reduced expression of CD39 and CD73 suggests promotion of ATP-dependent pro-inflammatory and reduction of adenosine-mediated anti-inflammatory mechanisms in migraine.
Transient receptor potential vanilloid type 1 (TRPV1) receptors activated by heat and capsaicin are expressed in trigeminal nociceptive neurons and implicated in the generation of migraine pain. Genetic studies suggested that single-nucleotide polymorphism (SNP) 1911A>G (rs8065080), leading to amino acid substitution Ile585Val, in the TRPV1 gene affects functional activity of TRPV1 receptors and is involved in different pain conditions. However, this polymorphism has not been tested in migraine patients. The objective of this pilot study was to investigate genetic factors of migraine susceptibility. We evaluated frequency distribution of AA, AG, and GG variants of SNP 1911A>G in the TRPV1 gene in patients with episodic and chronic migraine compared with healthy individuals. The study included 46 patients diagnosed with migraine (27 episodic and 19 chronic) and 50 healthy individuals as a control group. DNA from peripheral blood was used to test TRPV1 SNP using allelespecific PCR combined with gel electrophoresis. The genotype frequency distribution in episodic migraine was comparable with that in controls (AA 33%, AG 56%, GG 11% and AA 34%, AG 46%, GG 20%, respectively). On the contrary, in chronic migraine, the distribution differed significantly (p < 0.05) (AA 68%, AG 32%, GG 0%). This are first indications for a distinctive genotype frequency distribution of TRPV1 1911A>G in chronic migraine patients compared with episodic migraine patients and controls. Our data confirm a different predisposition to chronic pain in migraine and give a prerequisite for a new look at the nature of chronification of migraine, proposing that the absence of GG genotype may be considered as possible risk biomarker of episodic migraine evolution to chronic form.
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