Habituation of the Nociceptive Blink Reflex in Experimentally Induced Migraine Attack

• Status: Recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: IRCCS National Neurological Institute "C. Mondino" Foundation
• Collaborator: University of Pavia
• Treatments: Nitroglycerin

Criteria

Inclusion Criteria:

• Diagnosis of "1.1 Migraine without aura", according to ICHD-3 criteria, with a history of disease of at least one year;

• Frequency between 3 and 14 migraine days per month;

• Have completed a prospective headache diary for at least 1 month to confirm diagnosis and frequency.

Exclusion Criteria:

• Current or previous diagnosis of other forms of primary or secondary headache according to ICHD-3 criteria; it will be possible to enroll patients diagnosed with "2.1 Sporadic episodic tension-type headache", according to ICHD-3 criteria;

• Other conditions causing chronic pain;

• Significant cardiovascular disorders;

• History of other neurological or psychiatric disorders that may affect the study assessments;

• Contraindications or intolerance to the administration of Sumatriptan or NTG;

• Use of more than 1 preventive drug for the treatment of migraine, according to national guidelines;

• Change in the dosage of prevention treatment for migraine in the last month;

• Women in current or planned pregnancy, and breastfeeding;

• Chronic use of active ingredients with analgesic or sedative action (steroids, opioids, anti-inflammatories, paracetamol) or in any case capable of modifying the pain threshold (for example tricyclic antidepressants or serotonin reuptake inhibitors);

• Use of phosphodiesterase inhibitors.