Ictal adipokines are associated with pain severity and treatment response in episodic migraine.
OBJECTIVE
To evaluate ictal adipokine levels in episodic migraineurs and their association with pain severity and treatment response.


METHODS
This was a double-blind, placebo-controlled trial evaluating peripheral blood specimens from episodic migraineurs at acute pain onset and 30 to 120 minutes after treatment with sumatriptan/naproxen sodium vs placebo. Total adiponectin (T-ADP), ADP multimers (high molecular weight [HMW], middle molecular weight, and low molecular weight [LMW]), leptin, and resistin levels were evaluated by immunoassays.


RESULTS
Thirty-four participants (17 responders, 17 nonresponders) were included. In all participants, pretreatment pain severity increased with every quartile increase in both the HMW:T-ADP ratio (coefficient of variation [CV] 0.51; 95% confidence interval [CI]: 0.08, 0.93; p = 0.019) and resistin levels (CV 0.58; 95% CI: 0.21, 0.96; p = 0.002), but was not associated with quartile changes in leptin levels. In responders, T-ADP (CV -0.98; 95% CI: -1.88, -0.08; p = 0.031) and resistin (CV -0.95; 95% CI: -1.83, -0.07; p = 0.034) levels decreased 120 minutes after treatment as compared with pretreatment. In addition, in responders, the HMW:T-ADP ratio (CV -0.04; 95% CI: -0.07, -0.01; p = 0.041) decreased and the LMW:T-ADP ratio (CV 0.04; 95% CI: 0.01, 0.07; p = 0.043) increased at 120 minutes after treatment. In nonresponders, the LMW:T-ADP ratio (CV -0.04; 95% CI: -0.07, -0.01; p = 0.018) decreased 120 minutes after treatment. Leptin was not associated with treatment response.


CONCLUSIONS
Both pretreatment migraine pain severity and treatment response are associated with changes in adipokine levels. Adipokines represent potential novel migraine biomarkers and drug targets.
From the Department of Neurology (N.C.C., L.W.W., B.L.P.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Anesthesia (N.C.C.), University of California, San Francisco; Department of Epidemiology (B.G.), Harvard School of Public Health, Boston, MA; Department of Neurology (G.E.T.), University of Toledo, OH; Department of Neurology (P.D.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Nutrition Sciences (B.A.G.), University of Alabama at Birmingham; Department of Neurology (T.N.W.), Dartmouth Hitchcock Medical Center, Lebanon, NH; and Uniformed Services University (A.I.S.), Bethesda, MD.
Nu Cindy
NC
Chai
From the Department of Neurology (N.C.C., L.W.W., B.L.P.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Anesthesia (N.C.C.), University of California, San Francisco; Department of Epidemiology (B.G.), Harvard School of Public Health, Boston, MA; Department of Neurology (G.E.T.), University of Toledo, OH; Department of Neurology (P.D.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Nutrition Sciences (B.A.G.), University of Alabama at Birmingham; Department of Neurology (T.N.W.), Dartmouth Hitchcock Medical Center, Lebanon, NH; and Uniformed Services University (A.I.S.), Bethesda, MD.
Bizu
B
Gelaye
From the Department of Neurology (N.C.C., L.W.W., B.L.P.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Anesthesia (N.C.C.), University of California, San Francisco; Department of Epidemiology (B.G.), Harvard School of Public Health, Boston, MA; Department of Neurology (G.E.T.), University of Toledo, OH; Department of Neurology (P.D.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Nutrition Sciences (B.A.G.), University of Alabama at Birmingham; Department of Neurology (T.N.W.), Dartmouth Hitchcock Medical Center, Lebanon, NH; and Uniformed Services University (A.I.S.), Bethesda, MD.
Gretchen E
GE
Tietjen
From the Department of Neurology (N.C.C., L.W.W., B.L.P.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Anesthesia (N.C.C.), University of California, San Francisco; Department of Epidemiology (B.G.), Harvard School of Public Health, Boston, MA; Department of Neurology (G.E.T.), University of Toledo, OH; Department of Neurology (P.D.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Nutrition Sciences (B.A.G.), University of Alabama at Birmingham; Department of Neurology (T.N.W.), Dartmouth Hitchcock Medical Center, Lebanon, NH; and Uniformed Services University (A.I.S.), Bethesda, MD.
Paul D
PD
Dash
From the Department of Neurology (N.C.C., L.W.W., B.L.P.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Anesthesia (N.C.C.), University of California, San Francisco; Department of Epidemiology (B.G.), Harvard School of Public Health, Boston, MA; Department of Neurology (G.E.T.), University of Toledo, OH; Department of Neurology (P.D.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Nutrition Sciences (B.A.G.), University of Alabama at Birmingham; Department of Neurology (T.N.W.), Dartmouth Hitchcock Medical Center, Lebanon, NH; and Uniformed Services University (A.I.S.), Bethesda, MD.
Barbara A
BA
Gower
From the Department of Neurology (N.C.C., L.W.W., B.L.P.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Anesthesia (N.C.C.), University of California, San Francisco; Department of Epidemiology (B.G.), Harvard School of Public Health, Boston, MA; Department of Neurology (G.E.T.), University of Toledo, OH; Department of Neurology (P.D.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Nutrition Sciences (B.A.G.), University of Alabama at Birmingham; Department of Neurology (T.N.W.), Dartmouth Hitchcock Medical Center, Lebanon, NH; and Uniformed Services University (A.I.S.), Bethesda, MD.
Linda W
LW
White
From the Department of Neurology (N.C.C., L.W.W., B.L.P.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Anesthesia (N.C.C.), University of California, San Francisco; Department of Epidemiology (B.G.), Harvard School of Public Health, Boston, MA; Department of Neurology (G.E.T.), University of Toledo, OH; Department of Neurology (P.D.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Nutrition Sciences (B.A.G.), University of Alabama at Birmingham; Department of Neurology (T.N.W.), Dartmouth Hitchcock Medical Center, Lebanon, NH; and Uniformed Services University (A.I.S.), Bethesda, MD.
Thomas N
TN
Ward
From the Department of Neurology (N.C.C., L.W.W., B.L.P.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Anesthesia (N.C.C.), University of California, San Francisco; Department of Epidemiology (B.G.), Harvard School of Public Health, Boston, MA; Department of Neurology (G.E.T.), University of Toledo, OH; Department of Neurology (P.D.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Nutrition Sciences (B.A.G.), University of Alabama at Birmingham; Department of Neurology (T.N.W.), Dartmouth Hitchcock Medical Center, Lebanon, NH; and Uniformed Services University (A.I.S.), Bethesda, MD.
Ann I
AI
Scher
From the Department of Neurology (N.C.C., L.W.W., B.L.P.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Anesthesia (N.C.C.), University of California, San Francisco; Department of Epidemiology (B.G.), Harvard School of Public Health, Boston, MA; Department of Neurology (G.E.T.), University of Toledo, OH; Department of Neurology (P.D.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Nutrition Sciences (B.A.G.), University of Alabama at Birmingham; Department of Neurology (T.N.W.), Dartmouth Hitchcock Medical Center, Lebanon, NH; and Uniformed Services University (A.I.S.), Bethesda, MD. lpeterlin@jhmi.edu.
B Lee
BL
Peterlin
D054392:Adipokines / Q000097:blood*; D000328:Adult; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D009288:Naproxen / Q000008:administration & dosage / Q000494:pharmacology; D010919:Placebos; D012720:Severity of Illness Index; D018170:Sumatriptan / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D054392:Adipokines; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D010919:Placebos; D014662:Vasoconstrictor Agents; D009288:Naproxen; D018170:Sumatriptan