Novel capsaicin-induced parameters of microcirculation in migraine patients revealed by imaging photoplethysmography

Abstract

Background: The 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.

Methods: Fourteen 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.

Results: Blood 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.

Conclusion: BPA dynamics measured by imaging photoplethysmography could serve as a novel sensitive non-invasive biomarker of migraine-associated changes in microcirculation.

Keywords: CGRP; Capsaicin; Dermal blood flow; Imaging photoplethysmography; Microcirculation; Migraine; TRPV1.

Fig. 1

Experimental technique. a Layout of the setup for photoplethysmographic image acquisition simultaneously with ECG and b photograph of the unit containing digital camera and illuminator with eight green LEDs

Fig. 2

Typical example of PPG waveform measured in the upper arm. Waveform shown in (a) was recorded before application of the capsaicin patch, whereas that in (c) was recorded at about 15-th minute of the patch application. Black curves in (a) and (c) show synchronously recorded ECG. Thick lines in (b) and (d) show the shape of the signal after averaging over 20 cardiac cycles

Fig. 3

Evolution of the spatial distribution of blood pulsation amplitude in the upper arm during capsaicin application. BPA maps for migraine patients are shown in the upper raw (a-c) whereas those for healthy subjects are in the lower raw (d-f). The color scale on the right of each map shows BPA as AC/DC ratio in percent for each distribution, respectively. The moment of PPG recording is shown in the left lower corner of each map with reference to the beginning of capsaicin application

Fig. 4

The time course of blood perfusion changes during capsaicin application: an example of BPA evolution in four big ROIs representative for migraine patients (a), and an example for healthy subjects (b). Vertical dashed lines indicate the moments when the blood perfusion starts to grow (dashed green line) and when it was saturated (dashed red line)

Fig. 5

Parameters of capsaicin-induced blood perfusion in control and migraine groups. a Coefficient of variation and b delay time of capsaicin reaction in migraine patients and control group. Data presented as the mean (small squares), error of mean (boxes), and SD (whiskers). c Two-dimensional distribution for CV and DT in the Control and Migraine groups. Red circles are for migraine patients, and blue squares are for healthy subjects. The dashed red line shows the region of the predominant distribution of the parameters for migraine group, whereas the dashed blue line is for the control group

Fig. 6

Change of AC (panel a) and DC (panel b) components of the PPG waveform in control (blue) and migraine (red) groups after capsaicin application. The data are presented as the mean (small squares), error of mean (boxes), and SD (whiskers)