Habituation of the Nociceptive Blink Reflex in Experimentally Induced Migraine Attack

Summary

People with migraine typically show impaired responsivity to visual, auditory and pain stimuli (Burstein et al, 2015). The electrophysiological study of the nociceptive blink reflex (nBR) is widely adopted for the instrumental evaluation of trigeminal afferent function.

Migraine sufferers characteristically show deficits in the habituation to repeated stimulations of various sensory modalities, in the interictal phase of the disease (Bohotin et al, 2002; Di Clemente et al, 2005).

It has been described how the habituation / sensitization pattern presents a characteristic pattern over the course of the migraine cycle. Past evidence suggests that the habituation deficit may turn towards a normalization of the pattern near the acute migraine attack (Coppola et al, 2013; Katsarava et al, 2003).

However, the study of the spontaneous attack shows various limits and difficulties, mainly due to the impossibility of predicting the onset of the next attack and of standardizing the experimental conditions. The use of human models of migraine allows us to overcome these obstacles. Di Clemente et al. (2009) evaluated the electrophysiological changes in nBR after administration of nitroglycerin (NTG) in healthy subjects. The authors described a modification of trigeminal circuits and cortical responses (visual evoked potentials) after NTG. However, NTG administration does not induce migraine attack in healthy subjects, therefore this model cannot be directly translated to migraine pathology (Ashina et al. 2017).

Our group has previously used the human model of migraine based on the administration of NTG to study central and spinal level sensitization through the nociceptive avoidance reflex in the lower limb (RIII) (De Icco et al. 2020). The results of the previous study deepened our understanding of the central mechanisms of sensitization.

The investigation of the nBR allows to study the modulation of the caudal trigeminal complex (TCC). In the present study we therefore intend to evaluate, under well-controlled experimental conditions, the modulation of the trigeminal caudal complex during an experimentally induced migraine attack. The study will allow us to confirm or not the normalization of habituation described in the acute phase through the adoption of a solid cross-over and placebo-controlled study design.

Conditions

• Migraine
• Migraine Disorders
• Pain

Interventions

DRUG

Nitroglycerin

25 migraine patients without aura of both genders are randomized to receive a 20-minutes infusion of NTG and/or sterile saline on two days, with at least one week in between

DRUG

Saline

25 migraine patients without aura of both genders are randomized to receive a 20-minutes infusion of NTG and/or sterile saline on two days, with at least one week in between

Sponsors & Collaborators

• University of Pavia

  collaborator OTHER

• IRCCS National Neurological Institute "C. Mondino" Foundation

  lead OTHER

Principal Investigators

• Roberto De Icco, MD · IRCCS, Mondino Foundation

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-11-01

Primary Completion

2024-12-31

Completion

2024-12-31

Countries

• Italy

Study Locations