Glyceryl Trinitrate may Trigger Endogenous Nitric Oxide Production in Patients with Chronic Tension-Type Headache

Cephalalgia ◽  
2004 ◽  
Vol 24 (11) ◽  
pp. 967-972 ◽  
Author(s):  
M Ashina ◽  
H Simonsen ◽  
L Bendtsen ◽  
R Jensen ◽  
J Olesen
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Plasma Levels ◽  
Experimental Studies ◽  
Tension Type Headache ◽  
Primary Headaches ◽  
No Production ◽  
Chronic Tension Type Headache ◽  
Endogenous Production ◽  
Type Headache

Experimental studies in humans have shown that nitric oxide (NO) may play an important role in initiation of primary headaches. It has been proposed that activation of L-arginine-NO pathway and increased endogenous production of NO may be responsible for NO induced headache. NO is synthesized from L-arginine and that reaction also yields citrulline. In the present study we aimed to investigate plasma levels of citrulline and arginine as markers of NO production after infusion of the NO donor, glyceryl trinitrate (GTN). We recruited 16 patients with chronic tension-type headache and 16 healthy controls. The subjects were randomly allocated to receive 0.5 μg/kg/min GTN or placebo over 20 min. Patients were examined on headache free days. Blood samples were collected at baseline and 60 min after start of infusion. Both patients and controls developed stronger immediate headache on the GTN day than on the placebo day ( P = 0.008). The headache was more pronounced in patients than in controls ( P = 0.02). Plasma levels of citrulline increased significantly 60 min after start of GTN infusion compared to placebo infusion in patients ( P = 0.01) but not in controls ( P = 0.50). Plasma levels of arginine were unchanged in both patients ( P = 0.12) and controls ( P =0.18). We suggest that GTN administration may trigger endogenous production of NO in patients with chronic tension-type headache resulting in activation of perivascular sensory afferents.

Possible Mechanisms of Glyceryl-Trinitrate-Induced Immediate Headache in Patients With Chronic Tension-Type Headache

Cephalalgia ◽  
2000 ◽  
Vol 20 (10) ◽  
pp. 919-924 ◽  
Author(s):  
M Ashina ◽  
L Bendtsen ◽  
R Jensen ◽  
F Sakai ◽  
J Olesen
Keyword(s):  
Glyceryl Trinitrate ◽  
Myofascial Pain ◽  
Tension Type Headache ◽  
Primary Headaches ◽  
Heat Pain ◽  
Pain Thresholds ◽  
Chronic Tension Type Headache ◽  
Muscle Hardness ◽  
Pain Pathways ◽  
Type Headache

Nitric oxide (NO) plays an important role in the pathophysiology of primary headaches including chronic tension-type headache (CTTH). Thus, a NO synthase inhibitor reduces headache and muscle hardness while the NO donor glyceryl trinitrate (GTN) causes more headache in patients than in healthy controls. Sensitization of myofascial pain pathways is important in CTTH, and the aim of the present study was to investigate if such mechanisms may also explain GTN-induced immediate headache in patients with CTTH. In a randomized, double-blind, crossover study 16 patients with CTTH and 16 healthy subjects received intravenous infusion of GTN (0.5 μg/kg per min for 20 min) or placebo on two headache-free days separated by at least 1 week. Muscle hardness, myofascial tenderness, mechanical and heat pain thresholds were measured at baseline and at 60 min and 120 min after start of infusion. In patients, GTN infusion resulted in a biphasic response with immediate headache and more pronounced delayed headache. A similar but less pronounced response was seen in controls. There was no difference between GTN and placebo regarding muscle hardness, myofascial tenderness or pressure and heat pain thresholds in either patients or controls ( P > 0.05). The unchanged sensitivity of pericranial myofascial pain pathways indicates that peripheral and central sensitization is not involved in the mechanisms of GTN-induced immediate headache.

scholarly journals Calcitonin Gene-Related Peptide in Tension-Type Headache

2002 ◽  
Vol 2 ◽  
pp. 1527-1531 ◽  
Author(s):  
M. Ashina
Keyword(s):  
Plasma Levels ◽  
Calcitonin Gene Related Peptide ◽  
Tension Type Headache ◽  
Nerve Fibers ◽  
Primary Headaches ◽  
Chronic Tension Type Headache ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Type Headache

In the last 10 years there has been increasing interest in the role of calcitonin gene-related peptide (CGRP) in primary headaches. Tension-type headache is one of the most common and important types of primary headaches, and ongoing nociception from myofascial tissues may play an important role in the pathophysiology of this disorder. CGRP sensory fibers are preferentially located in the walls of arteries, and nerve fibers containing CGRP accompany small blood vessels in human cranial muscles. It is well established that nociception may lead to release of CGRP from sensory nerve endings and from central terminals of sensory afferents into the spinal cord. It has also been shown that density of CGRP fibers around arteries is increased in persistently inflamed muscle. These findings indicate that ongoing activity in sensory neurons in the cranial muscles may be reflected in changes of plasma levels of neuropeptides in patients with chronic tension-type headache. To explore the possible role of CGRP in tension-type headache, plasma levels of CGRP were measured in patients with chronic tension-type headache. This study showed that plasma levels of CGRP are normal in patients and unrelated to headache state. However, the findings of normal plasma levels of CGRP do not exclude the possibility that abnormalities of this neuropeptide at the neuronal or peripheral (pericranial muscles) levels play a role in the pathophysiology of tension-type headache. Investigation of CGRP in other compartments with new sensitive methods of analysis is necessary to clarify its role in tension-type headache.

Plasma levels of calcitonin gene-related peptide in chronic tension-type headache

Neurology ◽  
2000 ◽  
Vol 55 (9) ◽  
pp. 1335-1340 ◽  
Author(s):  
M. Ashina ◽  
L. Bendtsen ◽  
R. Jensen ◽  
S. Schifter ◽  
I. Jansen-Olesen ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Calcitonin Gene Related Peptide ◽  
Tension Type Headache ◽  
Chronic Tension Type Headache ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Type Headache

Abnormal Modulatory Influence of Diffuse Noxious Inhibitory Controls in Migraine and Chronic Tension-Type Headache Patients

Cephalalgia ◽  
2006 ◽  
Vol 26 (7) ◽  
pp. 782-789 ◽  
Author(s):  
G Sandrini ◽  
P Rossi ◽  
I Milanov ◽  
M Serrao ◽  
AP Cecchini ◽  
...  
Keyword(s):  
Cold Pressor Test ◽  
Cold Pressor ◽  
Tension Type Headache ◽  
Significant Inhibition ◽  
Pain Modulation ◽  
Primary Headaches ◽  
Diffuse Noxious Inhibitory Controls ◽  
Chronic Tension Type Headache ◽  
Subjective Pain ◽  
Type Headache

The aim of this study was to evaluate the function of pain modulating systems subserving diffuse noxious inhibitory controls (DNICs) in primary headaches. DNICs were examined in 24 migraineurs, 17 patients with chronic tension-type headache (CTTH) and 20 healthy subjects by means of nociceptive flexion RIII reflex and the cold pressor test (CPT) as heterotopic noxious conditioning stimulation (HNCS). The subjective pain thresholds (Tp) and the RIII reflex threshold (Tr) were significantly lower in CTTH vs. controls. In controls a significant inhibition of the RIII reflex was observed during the CPT (-30±, P < 0.05). Conversely, migraine and CTTH patients showed facilitation (+31±, P < 0.05 and +40±, P < 0.01, respectively) of the RIII reflex during the HNCS. This study demonstrates a dysfunction in systems subserving DNICs in both migraine and CTTH. Impairment of endogenous supraspinal pain modulation systems may contribute to the development and/or maintenance of central sensitization in primary headaches.

scholarly journals The Role of Single-Nucleotide Variants of NOS1, NOS2, and NOS3 Genes in the Comorbidity of Arterial Hypertension and Tension-Type Headache

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1556
Author(s):  
Natalia A. Shnayder ◽  
Marina M. Petrova ◽  
Polina V. Moskaleva ◽  
Pavel A. Shesternya ◽  
Elena A. Pozhilenkova ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Arterial Hypertension ◽  
Tension Type Headache ◽  
Small Sample ◽  
No Production ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Nos Inhibitors ◽  
Type Headache

Patients with tension-type headache (TTH) have an increased risk of developing arterial hypertension (AH), while hypertensive subjects do seem to have an increased risk of TTH. We searched for full-text English publications in databases using keywords and combined word searches over the past 15 years. In addition, earlier publications of historical interest were included in the review. In our review, we summed up the single nucleotide variants (SNVs) of Nitric Oxide Synthases (NOSs) genes involved in the development of essential AH and TTH. The results of studies we discussed in this review are contradictory. This might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical characteristics. However, the contribution of genetic and environmental factors remains understudied. This makes the issue interesting for researchers, as understanding these mechanisms can contribute to a search for new approaches to pathogenetic and disease-modifying treatment of the AH and TTH phenotype. New drugs against AH and TTH can be based on inhibition of nitric oxide (NO) production, blockade of steps in the NO-cGMP pathway, or NO scavenging. Indeed, selective neuronal NOS (n-NOS) and inducible NOS (i-NOS) inhibitors are already in early clinical development.

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