Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system

Abstract

Objective To evaluate, in vivo , the impact of ongoing chronic migraine (CM) attacks on the endogenous μ-opioid neurotransmission. Background CM is associated with cognitive-emotional dysfunction. CM is commonly associated with frequent acute medication use, including opioids. Methods We scanned 15 migraine patients during the spontaneous headache attack (ictal phase): 7 individuals with CM and 8 with episodic migraine (EM), as well as 7 healthy controls (HC), using positron emission tomography (PET) with the selective μ-opioid receptor (μOR) radiotracer [ 11 C]carfentanil. Migraineurs were scanned in two paradigms, one with thermal pain threshold challenge applied to the site of the headache, and one without thermal challenge. Multivariable analysis was performed between the μ-opioid receptor availability and the clinical data. Results μOR availability, measured with [ 11 C]carfentanil nondisplaceable binding potential (BP ND ), in the left thalamus (P-value = 0.005) and left caudate (P-value = 0.003) were decreased in CM patients with thermal pain threshold during the ictal phase relative to HC. Lower μOR BP ND in the right parahippocampal region (P-value = 0.001) and right amygdala (P-value = 0.002) were seen in CM relative to EM patients. Lower μOR BP ND values indicate either a decrease in μOR concentration or an increase in endogenous μ-opioid release in CM patients. In the right amygdala, 71% of the overall variance in μOR BP ND levels was explained by the type of migraine (CM vs. EM: partial-R 2 = 0.47, P-value<0.001, Cohen's effect size d = 2.6SD), the severity of the attack (pain area and intensity number summation [P.A.I.N.S.]: partial-R 2 = 0.16, P-value = 0.031), and the thermal pain threshold (allodynia: partial-R 2 = 0.08). Conclusions Increased endogenous μ-opioid receptor-mediated neurotransmission is seen in the limbic system of CM patients, especially in right amygdala, which is highly modulated by the attack frequency, pain severity, and sensitivity. This study demonstrates for the first time the negative impact of chronification and exacerbation of headache attacks on the endogenous μ-opioid mechanisms of migraine patients. ClinicalTrials.gov identifier: NCT03004313

Functional Alterations in the Posterior Insula and Cerebellum in Migraine Without Aura: A Resting-State MRI Study

“…Thus, greater DC value in the right amygdala in migraine patients with higher pain intensity may indicate amplification of nociception and increased emotional responses. In line with this view, a recent positron emission tomography study showed that lower μ-opioid receptor non-displaceable binding potential in the right amygdala greatly correlated with the severity of migraine attack and, to some extent, the decrease in the ictal thermal pain threshold in patients with chronic migraine (Jassar et al, 2019 ). Furthermore, we found a negative correlation between migraine frequency and FC between the left crus I and mPFC.…”

Sensory-Discriminative Three-Dimensional Body Pain Mobile App Measures Versus Traditional Pain Measurement With a Visual Analog Scale: Validation Study

“…Hence, the impact of pain chronification is linked to its area extension, which might be associated with the progression of central sensitization. For instance, molecular studies with positron emission tomography in chronic patients in vivo have shown that there is a dysfunction in the endogenous mu-opioid system that is highly related to years of pain or more specifically in migraine suffering and PAINS score [ 14 - 16 ]. This is arguably one of the main analgesic systems in our brains.…”

“…The AI-enabled time-stamped technology precisely and quantitatively records and communicates their pain(s) and associated symptoms, which better mirrors the way the brain decodes pain severity across the body. For instance, neuroimaging studies have reported that the level of endogenous μ-opioid activation in episodic and chronic migraine patients is highly affected by the pain area and intensity number summation (PAINS) [ 14 ], one of the main sensory pain measurements provided by GeoPain [ 14 - 16 ]. However, no correlations were found with μ-opioid receptor binding based on the attack pain intensity or area separately, or the traditional VAS score.…”

Differential alteration of fMRI signal variability in the ascending trigeminal somatosensory and pain modulatory pathways in migraine

“…The University of Michigan Institutional Review Board approved the study, and all participants provided written informed consent. Positron emission tomography (PET) data from the subset of the patients in the current study were previously published elsewhere [ 30 ].…”