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

Hassan Jassar, Thiago D. Nascimento, Niko Kaciroti, Marcos F. DosSantos, Theodora Danciu, Robert A. Koeppe, Yolanda R. Smith, Marcelo E. Bigal, Frank Porreca, Kenneth L. Casey, Jon Kar Zubieta, Alexandre F. DaSilva

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 [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

Original languageEnglish (US)
Article number101905
JournalNeuroImage: Clinical
Volume23
DOIs
StatePublished - Jan 1 2019

Fingerprint

Limbic System
Migraine Disorders
Synaptic Transmission
Opioid Analgesics
Opioid Receptors
carfentanil
Pain Threshold
Hot Temperature
Amygdala
Headache
Stroke
Pain
Hyperalgesia
Thalamus
Positron-Emission Tomography

Keywords

  • Central pain
  • Migraine
  • MRI
  • Opioid
  • PET
  • Thermal pain threshold

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

Cite this

Jassar, H., Nascimento, T. D., Kaciroti, N., DosSantos, M. F., Danciu, T., Koeppe, R. A., ... DaSilva, A. F. (2019). Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system. NeuroImage: Clinical, 23, [101905]. https://doi.org/10.1016/j.nicl.2019.101905

Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system. / Jassar, Hassan; Nascimento, Thiago D.; Kaciroti, Niko; DosSantos, Marcos F.; Danciu, Theodora; Koeppe, Robert A.; Smith, Yolanda R.; Bigal, Marcelo E.; Porreca, Frank; Casey, Kenneth L.; Zubieta, Jon Kar; DaSilva, Alexandre F.

In: NeuroImage: Clinical, Vol. 23, 101905, 01.01.2019.

Research output: Contribution to journalArticle

Jassar, H, Nascimento, TD, Kaciroti, N, DosSantos, MF, Danciu, T, Koeppe, RA, Smith, YR, Bigal, ME, Porreca, F, Casey, KL, Zubieta, JK & DaSilva, AF 2019, 'Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system', NeuroImage: Clinical, vol. 23, 101905. https://doi.org/10.1016/j.nicl.2019.101905
Jassar, Hassan ; Nascimento, Thiago D. ; Kaciroti, Niko ; DosSantos, Marcos F. ; Danciu, Theodora ; Koeppe, Robert A. ; Smith, Yolanda R. ; Bigal, Marcelo E. ; Porreca, Frank ; Casey, Kenneth L. ; Zubieta, Jon Kar ; DaSilva, Alexandre F. / Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system. In: NeuroImage: Clinical. 2019 ; Vol. 23.
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title = "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 [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",
keywords = "Central pain, Migraine, MRI, Opioid, PET, Thermal pain threshold",
author = "Hassan Jassar and Nascimento, {Thiago D.} and Niko Kaciroti and DosSantos, {Marcos F.} and Theodora Danciu and Koeppe, {Robert A.} and Smith, {Yolanda R.} and Bigal, {Marcelo E.} and Frank Porreca and Casey, {Kenneth L.} and Zubieta, {Jon Kar} and DaSilva, {Alexandre F.}",
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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, Frank

AU - Casey, Kenneth L.

AU - Zubieta, Jon Kar

AU - DaSilva, Alexandre F.

PY - 2019/1/1

Y1 - 2019/1/1

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 - Migraine

KW - MRI

KW - Opioid

KW - PET

KW - Thermal pain threshold

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