title: Nociception-specific blink reflex: pharmacology in healthy volunteers.
abstract: BACKGROUND
  The physiology and pharmacology of activation or perception of activation of pain-coding trigeminovascular afferents in humans is fundamental to understanding the biology of headache and developing new treatments.
  
  
  METHODS
  The blink reflex was elicited using a concentric electrode and recorded in four separate sessions, at baseline and two minutes after administration of ramped doses of diazepam (final dose 0.07 mg/kg), fentanyl (final dose 1.11 μg/kg), ketamine (final dose 0.084 mg/kg) and 0.9 % saline solution. The AUC (area under the curve, μV*ms) and the latency (ms) of the ipsi- and contralateral R2 component of the blink reflex were calculated by PC-based offline analysis. Immediately after each block of blink reflex recordings certain psychometric parameters were assessed.
  
  
  RESULTS
  There was an effect due to DRUG on the ipsilateral (F 3,60 = 7.3, P < 0.001) AUC as well as on the contralateral (F 3,60 = 6.02, P < 0.001) AUC across the study. A significant decrement in comparison to placebo was observed only for diazepam, affecting the ipsilateral AUC. The scores of alertness, calmness, contentedness, reaction time and precision were not affected by the DRUG across the sessions.
  
  
  CONCLUSIONS
  Previous studies suggest central, rather than peripheral changes in nociceptive trigeminal transmission in migraine. This study demonstrates a robust effect of benzodiazepine receptor modulation of the nociception specific blink reflex (nBR) without any μ-opiate or glutamate NMDA receptor component. The nociception specific blink reflex offers a reproducible, quantifiable method of assessment of trigeminal nociceptive system in humans that can be used to dissect pharmacology relevant to primary headache disorders.
authors.affiliation: NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital, London, UK.
authors.forename: J C A
authors.initials: JC
authors.lastname: Marin
authors.affiliation: NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital, London, UK.|Current address: Neurorehabilitation Center, RehaClinic, Bad Zurzach, Switzerland.|Current address: University of Zurich, Zürich, Switzerland.
authors.forename: A R
authors.initials: AR
authors.lastname: Gantenbein
authors.affiliation: NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital, London, UK.|Current address: Department of Neurology, Ghent University Hospital, Ghent, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Paemeleire
authors.affiliation: NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital, London, UK.|Neurology and Headache Center, Munich, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kaube
authors.affiliation: NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital, London, UK. peter.goadsby@kcl.ac.uk.|Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK. peter.goadsby@kcl.ac.uk.|Wellcome Foundation Building, King's College Hospital, London, SE5 9PJ, UK. peter.goadsby@kcl.ac.uk.
authors.forename: P J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D000328:Adult; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D019540:Area Under Curve; D001767:Blinking / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004558:Electric Stimulation; D064368:Healthy Volunteers; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D059225:Nociception / Q000187:drug effects*; D010147:Pain Measurement / Q000379:methods; D011594:Psychometrics; D055815:Young Adult
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D009125:Muscle Relaxants, Central
keywords: Migraine; Nociception specific blink reflex (nBR); Pharmacology; Trigeminovascular system