TY - JOUR
T1 - Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system
AU - Jassar, Hassan
AU - Nascimento, Thiago D.
AU - Kaciroti, Niko
AU - DosSantos, Marcos F.
AU - Danciu, Theodora
AU - Koeppe, Robert A.
AU - Smith, Yolanda R.
AU - Bigal, Marcelo E.
AU - Porreca, F.
AU - Casey, Kenneth L.
AU - Zubieta, Jon Kar
AU - DaSilva, Alexandre F.
N1 - Funding Information:
Supported by grants from the National Institute of Health – National Institute of Neurological Disorders and Stroke (NIH-NINDS K23 NS062946, R01 NS094413), USA; the Dana Foundation's Brain and Immuno-Imaging Award, USA; and the Migraine Research Foundation Research Grant Award, USA. This study is not industry-sponsored. We thank the technologists J. M. Rothley, E.J. McKenna, A.R. Weeden, P. K. and C. Hendriks for the help with PET scan at the PET Center Nuclear Medicine, and the Functional MRI Laboratory personnel, S. Peltier and K. Newnham.
Funding Information:
Supported by grants from the National Institute of Health – National Institute of Neurological Disorders and Stroke ( NIH-NINDS K23 NS062946 , R01 NS094413 ), USA; the Dana Foundation 's Brain and Immuno-Imaging Award, USA; and the Migraine Research Foundation Research Grant Award, USA. This study is not industry-sponsored.
Publisher Copyright:
© 2019 The Authors
PY - 2019
Y1 - 2019
N2 - 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 [11C]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 [11C]carfentanil nondisplaceable binding potential (BPND), 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 BPND 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 BPND 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 BPND levels was explained by the type of migraine (CM vs. EM: partial-R2 = 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-R2 = 0.16, P-value = 0.031), and the thermal pain threshold (allodynia: partial-R2 = 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
AB - 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 [11C]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 [11C]carfentanil nondisplaceable binding potential (BPND), 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 BPND 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 BPND 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 BPND levels was explained by the type of migraine (CM vs. EM: partial-R2 = 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-R2 = 0.16, P-value = 0.031), and the thermal pain threshold (allodynia: partial-R2 = 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
KW - Central pain
KW - MRI
KW - Migraine
KW - Opioid
KW - PET
KW - Thermal pain threshold
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U2 - 10.1016/j.nicl.2019.101905
DO - 10.1016/j.nicl.2019.101905
M3 - Article
C2 - 31279240
AN - SCOPUS:85068267068
VL - 23
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
SN - 2213-1582
M1 - 101905
ER -