Advantages of imaging photoplethysmography for migraine modeling: new optical markers of trigemino‐vascular activation in rats

Abstract

Background Existent animal models of migraine are not without drawbacks and limitations. The aim of our study was to evaluate imaging photoplethysmography (PPG) as a method of assessing intracranial blood flow in rats and its changes in response to electrical stimulation of dural trigeminal afferents. Methods Experiments were carried out with 32 anesthetized adult male Wistar rats. Trigeminovascular system (TVS) was activated by means of electrical stimulation of dural afferents through a closed cranial window (CCW). Parameters of meningeal blood flow were monitored using a PPG imaging system under green illumination with synchronous recording of an electrocardiogram (ECG) and systemic arterial blood pressure (ABP). Two indicators related to blood-flow parameters were assessed: intrinsic optical signals (OIS) and the amplitude of pulsatile component (APC) of the PPG waveform. Moreover, we carried out pharmacological validation of these indicators by determining their sensitivity to anti-migraine drugs: valproic acid and sumatriptan. For statistical analysis the non-parametric tests with post-hoc Bonferroni correction was used. Results Significant increase of both APC and OIS was observed due to CCW electrical stimulation. Compared to saline (n = 11), intravenous administration of both the sumatriptan (n = 11) and valproate (n = 10) by using a cumulative infusion regimen (three steps performed 30 min apart) lead to significant inhibitory effect on the APC response to the stimulation. In contrast, intravenous infusion of any substance or saline did not affect the OIS response to the stimulation. It was found that infusion of either sumatriptan or valproate did not affect the response of ABP or heart rate to the stimulation. Conclusions Imaging PPG can be used in an animal migraine model as a method for contactless assessment of intracranial blood flow. We have identified two new markers of TVS activation, one of which (APC) was pharmacologically confirmed to be associated with migraine. Monitoring of changes in APC caused by CCW electrical stimulation (controlling efficiency of stimulation by OIS) can be considered as a new way to assess the peripheral mechanism of action of anti-migraine interventions.

Duality in response of intracranial vessels to nitroglycerin revealed in rats by imaging photoplethysmography

“…In a simplified sense, a decrease in the tone of the vascular wall should be accompanied by an increase in APC, whereas an increase in tone should lead to a decrease in APC 53 . The results of studies carried out by our group using both unconditional vasodilating agents, such as CO 2 41 or the carbonic anhydrase inhibitor dorzolamide 40 , and neurogenic dural vasodilation 42 fully confirm such a performance.…”

“…Anesthesia and surgical preparations were performed as previously described 40 , 42 with minor modifications. Briefly, the rats were anesthetized by intraperitoneal injection with a mixture of urethane (Sigma, St. Louis, MO, USA) and a-chloralose (Sigma, St. Louis, MO, USA) at an initial dose of 800/60 mg/kg.…”

“…We have recently shown that a multimodal approach using imaging photoplethysmography (iPPG) at green illumination synchronized with the electrocardiogram (ECG) can serve as a reliable tool for studying intracranial blood flow in rats under various experimental conditions 39 – 41 . In particular, we identified new optical markers of trigeminal afferents activation and determined their sensitivity 42 to valproic acid and sumatriptan, two clinically effective drugs for preventive and abortive migraine treatment, respectively 43 . These features make it promising to use this approach to study various migraine-related interventions at the peripheral level of the trigeminovascular system.…”

Role of ATP in migraine mechanisms: focus on P2X3 receptors

“…Moreover, Piezo1 channels are expressed in trigeminal neurons [39,40] and it has been hypothesized they react to pulsatile blood flow by triggering spiking activity during a migraine attack [41]. It is tempting to speculate that direct mechanical activation of Piezo1 channels by pulsating vessels and ATP-dependent depolarization of meningeal afferents represent the basic mechanism of pulsatile migraine pain [39][40][41][42].…”