Brainstem functional oscillations across the migraine cycle: A longitudinal investigation

Meylakh, Noemi; Marciszewski, Kasia K.; Pietro, Flavia Di; Macefield, Vaughan G.; Macey, Paul M.; Henderson, Luke A.

doi:10.1016/j.nicl.2021.102630

Cited by 14 publications

(15 citation statements)

References 52 publications

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“…The brainstem activation in these two phases was also higher than it was during the interictal period. Neuroimaging findings have indicated the cyclic changes in brain activity during different phases of the migraine cycle, corroborating our observations of fluctuating activity [8,[11][12][13][31][32][33]. Increased brainstem activation preceding the migraine attack has been observed after trigeminal nociceptive stimulation [33], after noxious orofacial stimulation [34], and in the resting state [31] and is consistent with enhanced resting-state functional connectivity among brainstem nuclei or between brainstem and cortical regions [13,31].…”

Section: Dynamic Brain Activation During the Migraine Cyclesupporting

confidence: 87%

Dynamic brainstem and somatosensory cortical excitability during migraine cycles

et al. 2022

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Background Migraine has complex pathophysiological characteristics and episodic attacks. To decipher the cyclic neurophysiological features of migraine attacks, in this study, we compared neuronal excitability in the brainstem and primary somatosensory (S1) region between migraine phases for 30 consecutive days in two patients with episodic migraine. Methods Both patients underwent EEG recording of event-related potentials with the somatosensory and paired-pulse paradigms for 30 consecutive days. The migraine cycle was divided into the following phases: 24–48 h before headache onset (Pre2), within 24 h before headache onset (Pre1), during the migraine attack (Ictal), within 24 h after headache offset (Post1), and the interval of ˃48 h between the last and next headache phase (Interictal). The normalised current intensity in the brainstem and S1 and gating ratio in the S1 were recorded and examined. Results Six migraine cycles (three for each patient) were analysed. In both patients, the somatosensory excitability in the brainstem (peaking at 12–14 ms after stimulation) and S1 (peaking at 18–19 ms after stimulation) peaked in the Pre1 phase. The S1 inhibitory capability was higher in the Ictal phase than in the Pre1 phase. Conclusion This study demonstrates that migraine is a cyclic excitatory disorder and that the neural substrates involved include the somatosensory system, starting in the brainstem and spanning subsequently to the S1 before the migraine occurs. Further investigations with larger sample sizes are warranted.

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Section: Dynamic Brain Activation During the Migraine Cyclesupporting

confidence: 87%

Dynamic brainstem and somatosensory cortical excitability during migraine cycles

et al. 2022

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“…The enhanced sensitization of trigeminal and cervical areas observed in the preictal phase 7 could be evaluated as the behavioral consequence of the “activity‐dependent central sensitization” of second‐order neurons in the trigeminocervical complex mediated by the activation of diencephalon and brainstem areas 53 . This is supported by the observation that, during the preictal phase, diencephalon and brainstem areas increase their activation 44,45,60,61 and their functional connectivity with the trigeminocervical complex, 45 which also gradually increases its activity toward the next headache attack 62 …”

Section: Discussionmentioning

confidence: 94%

“…8,24 However, the present data showed consistent evidence of increased widespread sensitization in preictal EM, 7 with reduced mechanical pain threshold over the hand for two different sensory stimulus modalities. The preictal phase is characterized by activation of areas involved in pain processing and in descending modulation of nociceptive input 45,60,61,63 that could become dysfunctional, switching from being antinociceptive to pronociceptive leading to a migraine attack. 2,64-66 However, as other studies showed an increase of endogenous analgesic mechanisms in the preictal phase, 21,67 future longitudinal studies should assess the pain modulation (e.g., conditional pain modulation) 68,69 during the migraine cycle.…”

Section: Widespread Sensitizationmentioning

confidence: 99%

Trigeminal and cervical sensitization during the four phases of the migraine cycle in patients with episodic migraine

et al. 2022

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Objective Assessing mechanical pain thresholds from trigeminal, cervical, and distal pain‐free areas during the four phases of a migraine cycle in patients with episodic migraine (EM). Methods This multicenter, cross‐sectional, observational study conducted in Parma and Genoa’s Headache Centers assessed quantitative sensory tests during the four migraine phases in patients with EM compared to controls. Temporal summation of pain (TSP), static pressure pain threshold (sPPT), and mechanical pinprick pain threshold (MPT) were assessed from the trigeminal area, sPPT and dynamic PPT (dPPT) from the cervical area, sPPT and MPT over the hand, and sPPT from the tibialis anterior. Results A total of 135 patients and 46 controls were included. TSP was facilitated in ictal EM (EM vs. controls: mean [standard deviation] 2.7 [2.0] vs. 1.4 [1.8]; p = 0.004); trigeminal sPPT and MPT were reduced in interictal (sPPT: 198.5 [79.3] kPa; p = 0.021; MPT: 12.6 [15.7] g; p = 0.001), preictal (sPPT: 200.6 [71.6] kPa; p = 0.033; MPT: 10.7 [12.4] g; p < 0.001), ictal (sPPT: 171.4 [95.9] kPa; p < 0.001; MPT: 7.3 [12.0] g; p < 0.001), and postictal EM (sPPT: 182.2 [76.3] kPa; p = 0.006; MPT: 10.1 [14.9] g; p = 0.001), compared to controls (sPPT: 238.3 [73.8] kPa; MPT: 21.9 [17.3] g). Cervical sPPTs and dPPT were reduced in interictal (sPPT upper cervical spine: 420.5 [176.7] kPa; p = 0.031; sPPT lower cervical spine: 458.6 [207.3] kPa; p = 0.002; dPPT: 4826.5 [2698.0] g; p < 0.001), preictal (sPPT upper cervical spine: 389.3 [133.4] kPa; p = 0.006; sPPT lower cervical spine: 450.8 [174.3] kPa; p = 0.005; dPPT: 4184.2 [2628.3] g; p < 0.001), ictal (sPPT upper cervical spine: 379.9 [205.6] kPa p = 0.003; sPPT lower cervical spine: 436.3 [271.1] kPa; p = 0.001; dPPT: 3838.3 [2638.7] g; p < 0.001), and postictal EM (sPPT upper cervical spine: 385.5 [131.6] kPa; p = 0.020; sPPT lower cervical spine: 413.0 [150.3] kPa; p = 0.002; dPPT: 4679.6 [2894.9] g; p = 0.001), compared to controls (sPPT upper cervical spine: 494.9 [171.5] kPa; sPPT lower cervical spine: 586.9 [210.8] kPa; dPPT: 7693.9 [2896.8] g). Preictal EM had reduced hand sPPT and MPT (sPPT: 248.8 [96.6] kPa vs. 319.8 [112.3] kPa; p = 0.006; MPT: 23.6 [12.2] g vs. 32.5 [14.4] g; p = 0.035), while EM in the other phases showed reduction in hand MPT (interictal: 22.3 [15.6] g vs. 32.5 [14.4] g; p = 0.002; ictal: 22.4 [17.0] g vs. 32.5 [14.4] g; p = 0.004; postictal: 24.2 [18.8] g vs. 32.5 [14.4] g; p = 0.003) without significant reduction in hand sPPT. No difference in sPPT over the tibialis anterior was found. Hand MPT was negatively correlated with longer disease duration (r = −0.25; p = 0.011) and hand sPPT was negatively correlated with higher drug usage (r = −0.31; p = 0.002). TSP during the ictal phase was positively correlated with the physical (r = 0.38; p = 0.040) and emotional headache‐related disability (r = 0.53; p = 0.003). Conclusion In all phases of the migraine cycle, patients with EM show signs of sensitization in the trigeminocervical area, with patients with t...

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“…Furthermore, future investigations could also focus on changes in brainstem pain circuitry functioning within individual subjects to a greater extent in order to gain a more detailed understanding of changes in system functioning in individuals with chronic neuropathic pain. A similar approach has been used to study changes in brainstem function in individuals with migraine across the migraine cycle ( 31 , 166 ). For instance, it would be valuable to study changes in pain-modulation circuitry functioning over the course of an individual's pain development – from immediately following nerve injury throughout the development and persistence of long-term pain, and to explore whether there are changes in circuitry functioning following the administration of a standard pain treatment.…”

Section: Discussionmentioning

confidence: 99%

Brainstem Pain-Modulation Circuitry and Its Plasticity in Neuropathic Pain: Insights From Human Brain Imaging Investigations

2021

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Acute pain serves as a protective mechanism that alerts us to potential tissue damage and drives a behavioural response that removes us from danger. The neural circuitry critical for mounting this behavioural response is situated within the brainstem and is also crucial for producing analgesic and hyperalgesic responses. In particular, the periaqueductal grey, rostral ventromedial medulla, locus coeruleus and subnucleus reticularis dorsalis are important structures that directly or indirectly modulate nociceptive transmission at the primary nociceptive synapse. Substantial evidence from experimental animal studies suggests that plasticity within this system contributes to the initiation and/or maintenance of chronic neuropathic pain, and may even predispose individuals to developing chronic pain. Indeed, overwhelming evidence indicates that plasticity within this circuitry favours pro-nociception at the primary synapse in neuropathic pain conditions, a process that ultimately contributes to a hyperalgesic state. Although experimental animal investigations have been crucial in our understanding of the anatomy and function of the brainstem pain-modulation circuitry, it is vital to understand this system in acute and chronic pain states in humans so that more effective treatments can be developed. Recent functional MRI studies have identified a key role of this system during various analgesic and hyperalgesic responses including placebo analgesia, offset analgesia, attentional analgesia, conditioned pain modulation, central sensitisation and temporal summation. Moreover, recent MRI investigations have begun to explore brainstem pain-modulation circuitry plasticity in chronic neuropathic pain conditions and have identified altered grey matter volumes and functioning throughout the circuitry. Considering the findings from animal investigations, it is likely that these changes reflect a shift towards pro-nociception that ultimately contributes to the maintenance of neuropathic pain. The purpose of this review is to provide an overview of the human brain imaging investigations that have improved our understanding of the pain-modulation system in acute pain states and in neuropathic conditions. Our interpretation of the findings from these studies is often guided by the existing body of experimental animal literature, in addition to evidence from psychophysical investigations. Overall, understanding the plasticity of this system in human neuropathic pain conditions alongside the existing experimental animal literature will ultimately improve treatment options.

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Brainstem functional oscillations across the migraine cycle: A longitudinal investigation

Cited by 14 publications

References 52 publications

Dynamic brainstem and somatosensory cortical excitability during migraine cycles

Dynamic brainstem and somatosensory cortical excitability during migraine cycles

Trigeminal and cervical sensitization during the four phases of the migraine cycle in patients with episodic migraine

Brainstem Pain-Modulation Circuitry and Its Plasticity in Neuropathic Pain: Insights From Human Brain Imaging Investigations

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