Suboccipital cerebrospinal fluid and plasma concentrations of somatostatin, neuropeptide Y and beta-endorphin in patients with common migraine

doi:10.1016/0143-4179(92)90065-5

Neuropeptides

Volume 22, Issue 2, June 1992, Pages 111-116

https://doi.org/10.1016/0143-4179(92)90065-5 Get rights and content

Abstract

The somatostatin-like (SLI), the neuropeptide Y-like (NPY-LI), and the betaendorphin-like (BE-LI) immunoreactivities of cerebrospinal fluid (CSF) obtained by suboccipital puncture, or plasma from patients suffering from common migraine or other neuropsychiatric disorders were analysed. The SLI concentration was tendentiously decreased in the migraine patients during the attack-free period compared to that of a ‘mixed neuropsychiatric group’. During the migraine attack the level of SLI was further decreased. Similar alteration was found in the CSF BE-LI, while the BE-LI in the plasma showed only a tendentious decrease in common migraine patients. The NPY-LI did not change during the attack period in the CSF or plasma. These findings may indicate the possible role of somatostatin in the pathogenesis of common migraine, and support earlier observations that beta-endorphin is involved in the development in this disorder.

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Cited by (43)

Effects of somatostatin, a somatostatin agonist, and an antagonist, on a putative migraine trigger pathway
2024, Neuropeptides
To determine whether somatostatin (SST) could be a cortico-brainstem neurotransmitter involved in producing the headache of migraine.
There is evidence to support the idea that a cortico-brainstem-trigeminal nucleus neuraxis might be responsible for producing migraine headache; we have suggested that SST may be one of the neurotransmitters involved.
Rats were anesthetised and prepared for recording neurons in either the periaqueductal gray matter (PAG) or nucleus raphe magnus (NRM), as well as the trigeminal nucleus caudalis (TNC). The dura mater and facial skin were stimulated electrically or mechanically. SST, the SST agonist L054264 and the SST antagonist CYN54806 were injected intravenously, by microinjection, or by iontophoresis into the PAG or NRM. Cortical neuronal activity was provoked by cortical spreading depression (CSD) or light flash (LF) and was monitored by recording cortical blood flow (CBF).
Intravenous injection of SST: (a) selectively decreased the responses of TNC neurons to stimulation of the dura, but not skin, for up to 5 h; (b) decreased the ongoing discharge rate of TNC neurons while simultaneously increasing the discharge rate of neurons in either brainstem nucleus and; (c) prevented, or reversed, the effect of CSD and LF on brainstem and trigeminal neuron discharge rates. CSD and LF decreased the discharge rate of neurons in both brainstem nuclei and increased the discharge rate of TNC neurons. These effects were reversed by L054264 and mimicked by CYN54806. Injections of L054264 into the PAG or NRM reduced the response of TNC neurons to dural stimulation and skin stimulation differentially, depending on the nucleus injected. Injections of CYN54806 into either brainstem nucleus potentiated the responses of TNC neurons to dural and skin stimulation, but without a marked differential effect.
These results imply that SST could be a neurotransmitter in a pathway responsible for migraine pain.
Cross talk about the role of Neuropeptide Y in CNS disorders and diseases
2023, Neuropeptides
A peptide composed of a 36 amino acid called Neuropeptide Y (NPY) is employed in a variety of physiological processes to manage and treat conditions affecting the endocrine, circulatory, respiratory, digestive, and neurological systems. NPY naturally binds to G-protein coupled receptors, activating the Y-receptors (Y1-Y5 and y6). The findings on numerous therapeutic applications of NPY for CNS disease are presented in this review by the authors. New targets for treating diseases will be revealed by medication combinations that target NPY and its receptors. This review is mainly focused on disorders such as anxiety, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Machado Joseph disease, multiple sclerosis, schizophrenia, depression, migraine, alcohol use disorder, and substance use disorder. The findings from the preclinical studies and clinical studies covered in this article may help create efficient therapeutic plans to treat neurological conditions on the one hand and psychiatric disorders on the other. They may also open the door to the creation of novel NPY receptor ligands as medications to treat these conditions.
Does somatostatin have a role to play in migraine headache?
2018, Neuropeptides
Citation Excerpt :
Brain and CSF levels of SST are low in patients with various psychiatric conditions (depression, schizophrenia) and neurological conditions (Alzheimer's disease, Huntington's disease, multiple sclerosis, Parkinson's disease) –reviewed in Vécsei and Widerlöv (Vecsei and Widerlöv, 1988). Vécsei et al.(Vécsei et al., 1992) were among the first to report that CSF SST levels were also low in migraineurs interictally and even lower during the headache phase. Similar findings were later made by Sarchielli et al.(Sarchielli et al., 2006).
Migraine is a condition without apparent pathology. Its cardinal symptom is the prolonged excruciating headache. Theories about this pain have posited pathologies which run the gamut from neural to vascular to neurovascular, but no observations have detected a plausible pathology. We believe that no pathology can be found for migraine headache because none exists. Migraine is not driven by pathology – it is driven by neural events produced by triggers – or simply by neural noise- noise that has crossed a critical threshold. If these ideas are true, how does the pain arise? We hypothesise that migraine headache is a consequence of withdrawal of descending pain control, produced by “noise” in the cerebral cortex. Nevertheless, there has to be a neural circuit to transform cortical noise to withdrawal of pain control. In our hypothesis, this neural circuit extends from the cortex, synapses in two brainstem nuclei (the periaqueductal gray matter and the raphe magnus nucleus) and ultimately reaches the first synapse of the trigeminal sensory system. The second stage of this circuit uses serotonin (5HT) as a neurotransmitter, but the neuronal projection from the cortex to the brainstem seems to involve relatively uncommon neurotransmitters. We believe that one of these is somatostatin (SST). Temporal changes in levels of circulating SST mirror the temporal changes in the incidence of migraine, particularly in women. The SST₂ receptor agonist octreotide has been used with some success in migraine and cluster headache. A cortical to PAG/NRM neural projection certainly exists and we briefly review the anatomical and neurophysiological evidence for it and provide preliminary evidence that SST may the critical neurotransmitter in this pathway. We therefore suggest that the withdrawal of descending tone in SST-containing neurons, might create a false pain signal and hence the headache of migraine.
Primary headaches
2017, Handbook of Clinical Neurology
Citation Excerpt :
In blood, β-EP concentrations were also decreased in interictal, ictal, and chronic migraineurs. For an opioid molecule one would expect different levels during headache attacks compared to the pain-free state, although this was not clearly observed in individual studies (Baldi et al., 1982; Bach et al., 1985; Vécsei et al., 1992). Additionally, it remains unclear whether these changes are specific for migraine or reflect frequent pain exposure.
Headache disorders, characterized by recurrent headache, are among the most common disorders of the nervous system. Primary headache disorders are by definition not the result of any other underlying disease or process. In this chapter the current status of cerebrospinal fluid (CSF) research and applications for clinical practice for the three main primary headaches – migraine, cluster headache, and tension-type headache – will be described. Primary headaches are clinically diagnosed disorders, with typically normal routine CSF measurements. Research in these headaches has been focused on identifying pathophysiologic pathways with a wide array of measured molecules. CSF research in the headache field is still in the discovery phase, with most studies performed in migraine and with unreplicated findings for most of the identified molecules. From a clinical standpoint it would be of great value if CSF biomarkers could be used as disorder-specific biomarkers for difficult primary headache cases, or to predict treatment responsiveness or risk for headache chronification. These applications are currently not yet feasible. For future research into CSF biomarkers for primary headache disorders, two different strategies should be employed: hypothesis-driven and nonhypothesis-driven biochemical research, to show new avenues for treatment strategies and develop prediction models for clinical use.
Migraine and neuropeptides
2015, Neuropeptides
Citation Excerpt :
A preclinical animal study has revealed that blockade of the SST receptors by the administration of cyclo-SST to the posterior hypothalamic area of the rat resulted in an antinociceptive effect on the dural electrical and facial thermal inputs in the TNC (Bartsch et al., 2005). In an early clinical study, the SST immunoreactivity in the suboccipital CSF was decreased in migraine patients without aura during the attack-free periods, subsequently further decreasing and reaching statistically significant difference as compared with a mixed neuropsychiatric group of patients (Vecsei et al., 1992). CSF obtained by lumbar puncture exhibited a lower SST immunoreactivity level in chronic migraine patients than in controls (Sarchielli et al., 2006a).
Migraine is a common disabling neurovascular primary headache disorder. The pathomechanism is not clear, but extensive preclinical and clinical studies are ongoing. The structural basis of the leading hypothesis is the trigeminovascular system, which includes the trigeminal ganglion, the meningeal vasculature, and the distinct nuclei of the brainstem, the thalamus and the somatosensory cortex. This review covers the effects of sensory (calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide and substance P), sympathetic (neuropeptide Y) and parasympathetic (vasoactive intestinal peptide) migraine-related neuropeptides and the functions of somatostatin, nociceptin and the orexins in the trigeminovascular system. These neuropeptides may take part in neurogenic inflammation (plasma protein extravasation and vasodilatation) of the intracranial vasculature and peripheral and central sensitization of the trigeminal system. The results of human clinical studies are discussed with regard to the alterations in these neuropeptides in the plasma, saliva and cerebrospinal fluid during or between migraine attacks, and the therapeutic possibilities involving migraine-related neuropeptides in the acute and prophylactic treatment of migraine headache are surveyed.
Peripheral and central alterations of pituitary adenylate cyclase activating polypeptide-like immunoreactivity in the rat in response to activation of the trigeminovascular system
2012, Peptides
Citation Excerpt :
The lack of change in PACAP expression in the TRG in our experiments might be related to the fact that we applied acute stimulations, and not peripheral nerve damage, or that the short stimulation period and latency was not sufficient to cause substantial expression changes. An earlier study revealed decreased somatostatin- and beta-endorphin-like immunoreactivities of plasma or CSF obtained by suboccipital puncture, while the neuropeptide Y-like immunoreactivity did not change during the attack period in patients suffering from common migraine [92]. The present MS results confirmed the RIA detection of the presence of PACAP-38 in the rat plasma.
Pituitary adenylate cyclase activating polypeptide (PACAP) is present in the cranial arteries and trigeminal sensory neurons. We therefore examined the alterations in PACAP-like immunoreactivity (PACAP-LI) in a time-dependent manner in two rat models of trigeminovascular system (TS) activation. In one group chemical stimulation (CS) was performed with i.p. nitroglycerol (NTG), and in the other one the trigeminal ganglia (TRG) were subjected to electrical stimulation (ES). The two biologically active forms, PACAP-38 and PACAP-27, were determined by means of radioimmunoassay (RIA) and mass spectrometry (MS) in the plasma, the cerebrospinal fluid (CSF), the trigeminal nucleus caudalis (TNC), the spinal cord (SC) and the TRG. The tissue concentrations of PACAP-27 were 10 times lower than those of PACAP-38 in the TNC and SC, but about half in the TRG. PACAP-38, but not PACAP-27, was present in the plasma. Neither form could be identified in the CSF. PACAP-38-LI in the plasma, SC and TRG remained unchanged after CS, but it was increased significantly in the TNC 90 and 180 min after NTG injection. In response to ES of the TRG, the level of PACAP-38 in the plasma and the TNC was significantly elevated 90 and 180 min later, but not in the SC or the TRG. The alterations in the levels of PACAP-27 in the tissue homogenates in response to both forms of stimulation were identical to those of PACAP-38. The selective increases in both forms of PACAP in the TNC suggest its important role in the central sensitization involved in migraine-like headache.

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Suboccipital cerebrospinal fluid and plasma concentrations of somatostatin, neuropeptide Y and beta-endorphin in patients with common migraine

Abstract

Prog. Neuro-Psychopharmacol. Biol. Psychiat.

Peptides

J. psychiat. Res.

Regul. Pept.

Biol. Psychiatry

Peptides

Review article: Current thoughts on migraine

Headache

Migraine: clinical features, mechanisms and management

The hypothalamus and the aetiology of migraine

The regional distribution of somatostatin in the rat

Endocrinology

Brain and CSF somatostatin concentrations in patients with psychiatric and neurological illness. An overview

Acta Psychiatr. Scand.

Neuropeptide Y: Complete amino acid sequence of the brain peptide

Neuropeptide Y. An overview of central distribution, functional aspects, and possible involvement in neuropsychiatric illnesses

Acta Psychiatr. Scand.

The cardiovascular effects of neuropeptide Y (NPY)

Clin. Exp. Hypertens.