The Effects of a Long-lasting Infusion of Vasoactive Intestinal Peptide (VIP) in Episodic Migraine Patients
Condition: Migraine; Pain; Neurologic Manifestations; Signs and Symptoms; Brain Diseases; Central Nervous System Diseases
MeSH terms: Migraine Disorders; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases; Neurologic Manifestations
Study type: Interventional

Summary: 
      Vasoactive intestinal peptide (VIP) is a peptide of 28 amino acid residues that belongs to
      the glucagon/secretin superfamily of peptides. Along with other neuropeptides, such as
      calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide
      (PACAP), it is released from the trigeminal afferents and exerts a strong vasodilating
      activity on the cranial vasculature. Especially, it shares 70% structure with PACAP and acts
      on the same receptors. But, unlike it, VIP cannot induce a long-lasting vasodilation and has
      a modest capability to induce migraine attacks. Whether it may induce migraine-like attacks
      in migraine patients, as a twenty-minute infusion of PACAP, is unknown.
    

Detailed description: 
      The vasoactive intestinal polypeptide (VIP) is a peptide of 28 amino acid residues that
      belongs to the glucagon/secretin superfamily of peptides. It is distributed in different
      regions of the nervous system, including several autonomic ganglia and the brain. Once
      released from neurons, it acts on the vasoactive intestinal peptide receptor 1 (VPAC1), the
      vasoactive intestinal peptide receptor 2 (VPAC2) and the pituitary adenylate
      cyclase-activating polypeptide type I receptor (PAC1). All three belong to a family of
      G-protein coupled receptors, sharing the activation of adenylate cyclase and the increase in
      intracellular cyclic adenosine monophosphate (cAMP). The three receptors are involved in many
      physiological functions, among them the vasodilating and parasympathetic responses. VPAC1 and
      VPAC2 are expressed in dura mater vessels and are primarily responsible for the relaxation of
      arteries. PAC1 is located in the trigemino-autonomic system, but not in blood vessels. VIP
      shares the binding to the three aforementioned receptors with other peptides, including the
      pituitary adenylate cyclase-activating polypeptide-38 (PACAP38), and the pituitary adenylate
      cyclase-activating polypeptide-27 (PACAP27).

      20-minute infusion of VIP and PACAPs in patients with migraine dilated cranial arteries.
      However, only PACAP27 and PACAP38 induced a sustained cranial vasodilation, and migraine
      like-attacks. VIP-induced cranial vasodilation was of short duration, and patients did not
      report migraine-like attacks. The discrepancy was ascribed to the preferential activation of
      the PAC1 receptor by PACAPs, but a monoclonal antibody against PAC1 receptor recently failed
      in migraine prevention. Currently, it is unknown whether the prolonged cranial vasodilation
      related with the appearance of migraine-like attacks. More recently, a two-hour infusion of
      VIP promoted a long-lasting cranial vasodilation and delayed headache in healthy volunteers,
      resembling the effect of PACAP27 and PACAP38, two closely related peptides causing migraine.
      Whether a long-lasting infusion of VIP may induce a sustained cranial vasodilation and
      migraine-like attacks in migraine patients, as a twenty-minute infusion of PACAP27 and
      PACAP38, is unknown.
    

Intervention name(s): Vasoactive Intestinal Polypeptide (VIP); Sterile saline
Intervention type(s): Drug; Drug
Intervention description(s): 20 episodic migraine patients without aura of both genders are randomized to receive a 2-hour infusion of VIP and/or sterile saline on two days, with at least one week in between.; 20 episodic migraine patients without aura of both genders are randomized to receive a 2-hour infusion of VIP and/or sterile saline on two days, with at least one week in between.
Other intervention name(s): Vasoactive Intestinal Peptide (VIP); Isotonic saline; 0.9% saline
Intervention MeSH terms: Vasoactive Intestinal Peptide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other