title: Dopamine D2/D3 imbalance during migraine attack and allodynia in vivo.
abstract: OBJECTIVE
  To evaluate in vivo the dynamics of endogenous dopamine (DA) neurotransmission during migraine ictus with allodynia.
  
  
  METHODS
  We examined 8 episodic migraineurs and 8 healthy controls (HC) using PET with [11C]raclopride. The uptake measure of [11C]raclopride, nondisplaceable binding potential (BPND), would increase when there was a reduction in endogenous DA release. The opposite is true for a decrease in [11C]raclopride BPND. Patients were scanned twice: one PET session was during a spontaneous migraine ictus at rest, followed by a sustained thermal pain threshold (STPT) challenge on the trigeminal region, eliciting an allodynia experience; another was during interictal phase.
  
  
  RESULTS
  Striatal BPNDof [11C]raclopride in migraineurs did not differ from HC. We found a significant increase in [11C]raclopride BPNDin the striatum region of migraineurs during both headache attack and allodynia relative to interictal phase. However, when compared to the migraine attack at rest, migraineurs during the STPT challenge had a significant sudden reduction in [11C]raclopride BPNDin the insula. Such directional change was also observed in the caudate of HC relative to the interictal phase during challenge. Furthermore, ictal changes in [11C]raclopride BPNDin migraineurs at rest were positively correlated with the chronicity of migraine attacks, and negatively correlated with the frequency during challenge.
  
  
  CONCLUSIONS
  Our findings demonstrate that there is an imbalanced uptake of [11C]raclopride during the headache attack and ictal allodynia, which indicates reduction and fluctuation in ictal endogenous DA release in migraineurs. Moreover, the longer the history and recurrence of migraine attacks, the lower the ictal endogenous DA release.
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor. adasilva@umich.edu.
authors.forename: Alexandre F
authors.initials: AF
authors.lastname: DaSilva
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Thiago D
authors.initials: TD
authors.lastname: Nascimento
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Hassan
authors.initials: H
authors.lastname: Jassar
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Joseph
authors.initials: J
authors.lastname: Heffernan
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Toback
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Sarah
authors.initials: S
authors.lastname: Lucas
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Marcos F
authors.initials: MF
authors.lastname: DosSantos
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Bellile
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Boonstra
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Jeremy M G
authors.initials: JMG
authors.lastname: Taylor
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Casey
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Yolanda R
authors.initials: YR
authors.lastname: Smith
authors.affiliation: From the Headache & Orofacial Pain Effort (H.O.P.E.), Biologic & Materials Sciences Department, School of Dentistry (A.F.D., T.D.N., H.J., R.L.T., S.L., M.F.D.), Translational Neuroimaging Laboratory, Molecular & Behavioral Neuroscience Institute (A.F.D., J.H.. J.-K.Z.), Department of Biostatistics (E.L.B., P.S.B., J.M.G.T.), Department of Neurology (K.L.C.), PET Physics Section, Division of Nuclear Medicine, Radiology Department (R.A.K.), and Department of Obstetrics and Gynecology (Y.R.S.), University of Michigan, Ann Arbor.
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D020325:Migraine with Aura / Q000000981:diagnostic imaging / Q000378:metabolism*; D020326:Migraine without Aura / Q000000981:diagnostic imaging / Q000378:metabolism*; D010812:Physical Stimulation; D049268:Positron-Emission Tomography; D020891:Raclopride; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012146:Rest; D009435:Synaptic Transmission / Q000502:physiology; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; C493593:DRD3 protein, human; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride; D004298:Dopamine