Plasma Nociceptin Levels are Reduced in Migraine without Aura

Abstract

It was demonstrated that both nociceptin, a novel opioid neuropeptide, and its receptor are present in trigeminovascular neurons. In an animal model nociceptin dose-dependently inhibited neurogenic dural vasodilatation. These results suggest that nociceptin may be involved in neurovascular headaches such as migraine. To test this hypothesis, we studied circulating nociceptin levels in 18 patients suffering from migraine without aura and in 24 controls. Headache-free migraineurs had significantly lower nociceptin levels than controls (5.79 +/- 1.82 vs. 9.74 +/- 2.43 pg/ml, P < 0.0001, Student's t-tests). Nociceptin levels were further reduced in six patients studied in the first 3 h of typical migraine attacks (1.04 +/- 0.17 pg/ml). Nociceptin levels correlated with the frequency of attacks in this group of migraineurs. Lower interictal nociceptin levels may contribute to a defective regulation of trigeminovascular neurons in migraineurs which might be important in the pain process of migraine.

Migraine and neuropeptides

“…in the hypothalamus, the brainstem and the dorsal horn of the spinal cord (Bridge et al, 2003;Mollereau and Mouledous, 2000). NOP has multidirectional effects in the CNS, exerting algesic, hyperalgesic and analgesic properties, while in the PNS it displays antinociceptive effects (Ertsey et al, 2005;Giuliani et al, 2000;Meunier et al, 2000;Reinscheid et al, 2000). In tracing experiments with immunohistochemical visualization, NOP-ir fibres of trigeminal origin were detected in the dorsal horn of the cervical spinal cord (Marfurt and Del Toro, 1987).…”

“…In this experimental set-up, intravenously administered NOP dose-dependently suppressed the neurogenic dural vasodilatation via NOP1 receptor activation (Bartsch et al, 2002). A clinical study of the circulating NOP revealed a lower plasma NOP level in migraine patients without aura during the headache-free period than in controls, and the level correlating with the attack frequency (Ertsey et al, 2005).…”

“…NOP does not influence the contractile properties of the human cerebral arteries (Hou et al, 2003). The migraine-related CNS structures, such as the TNC, LC, PAG, raphe nuclei, thalamus and sensory cortex, display NOP1 receptor expression (Ertsey et al, 2005). The meningeal vasculature is densely innervated by trigeminal sensory nerve fibres (unmyelinated C-fibres and thinly myelinated Aδ fibres), and their activation can result in neurogenic inflammation as a source of migraine pain (Edvinsson and Goadsby, 1998;Edvinsson and Uddman, 2005).…”

Selected Confirmed, Probable, and Exploratory Migraine Biomarkers

“…May indicate impaired pineal function in migraine. Of note, melatonin infusion improved some migraine symptoms.Decreased nocturnal plasma melatonin levelsMigraine with and without aura compared to controlsPlasma RIATrait 153 When depressed patients excluded, decrease was significant only in females with migraine.Decreased plasma nociceptin levelsMigraine without aura compared to controlsPlasma assayState (during headache) and trait (interictal) 154 Levels are lower in migraineurs than controls interictally, and decrease further during first 3 hours of an attack. Correlate with frequency of attacks.…”

Decreased plasma nociceptin/orphanin FQ levels after acute coronary syndromes

“…In spite of the growing evidence that N/OFQ has a signifi cant role in cardiovascular regulation, studies having been made so far have concentrated mainly on its function in pain sensation and its possible use as a novel analgesic (9). Given that our limited knowledge on the N/OFQ system is based on studies made on rodents, human physiology remains relatively unclear (8).…”