[Interdisciplinary treatment of headache. The Danish Society of Headache].
Explore the source record for details and available documents.
Denmark↗
Biomedical subjects
Jes Olesen
Publications and source records attributed to Jes Olesen.
Evidence for a separate type of migraine with aura: sporadic hemiplegic migraine.
OBJECTIVE: To compare clinical characteristics of patients with sporadic hemiplegic migraine (SHM) with those of patients with migraine with typical aura (MA) and patients with familial hemiplegic migraine (FHM). METHODS: The authors used a computer search of Denmark's National Patient Register to screen the population for patients with migraine with aura with motor weakness, and also examined case records from headache clinics and private practicing neurologists and placed advertisements. The authors screened patients and their relatives with a semi-structured validated telephone interview. All recruited patients were then interviewed by a physician and given a neurologic examination. RESULTS: A total of 105 patients with SHM were identified. Seventy-two percent had four typical aura symptoms: visual, sensory, aphasic, and motor. All had at least two symptoms present during SHM attacks. A gradual progression and sequential appearance of aura symptoms was typical; compared with MA, the duration of each aura symptom was usually prolonged and bilateral motor symptoms were more frequent. Of the patients with SHM, 72% fulfilled the criteria for basilar migraine during SHM attacks. The aura was usually followed by headache, as is common in FHM but not MA. CONCLUSIONS: Patients with sporadic hemiplegic migraine had clinical symptoms identical to familial hemiplegic migraine and significantly different from migraine with typical aura. Sporadic hemiplegic migraine is a separate entity, and should be classified with familial hemiplegic migraine.
Adolescent↗
Experimental muscle pain and tenderness following infusion of endogenous substances in humans.
Several human models of myofascial pain exist, but none are similar to clinical pain. The aim of the present study was to develop a clinically relevant model of prolonged human myofascial pain using infusion of the naturally occurring endogenous substances. Initially, bradykinin (Bk), serotonin (5-hydroxytryptamine (5-HT)), histamine (His), prostaglandin E(2) (PGE(2)), adenosine-tri-phosphate (ATP), and their combinations were infused into the trapezius muscle of 36 healthy subjects in a total of 67 sessions to identify substances, which could induce a moderate muscle pain. PGE(2), ATP, and a combination of Bk, 5-HT, His, and PGE(2) produced the intended moderate pain. These substances were further examined in a randomised, blinded, placebo-controlled dose-finding design in 15 healthy subjects in 68 sessions. PGE(2) (3, 6, and 12 nmol/ml) induced mild pain and tenderness not different from placebo. ATP (9000, 18,000, and 36,000 nmol/ml) induced pain of moderate to strong intensity (P=0.04) and the dose of 18,000 nmol/ml furthermore produced moderate local tenderness (P=0.04). Because of unacceptable side effects in subsequent examinations, further studies of ATP in humans were suspended. Infusion of the combination of Bk (92 nmol), 5-HT (156 nmol), His (140 nmol), and PGE(2) (1.95 nmol) produced a moderate pain intensity (P=0.04) and mild tenderness (P=0.04) without inducing unacceptable side effects. Intramuscular infusion of a combination of Bk, 5-HT, His, and PGE(2) induced a prolonged moderate pain and tenderness in healthy humans, and this model may be a valuable tool in future studies of the pathophysiological mechanisms of myofascial pain.
Adult↗
Migraine can be induced by sildenafil without changes in middle cerebral artery diameter.
Migraine is considered a neurovascular disease involving dilatation of cerebral arteries. Nitric oxide (NO) donors induce dilatation of cerebral and extracranial arteries and migraine, but NO has several mechanisms of action in addition to its cyclic guanosine monophosphate (cGMP)-mediated vasodilatation. We examined whether sildenafil (Viagra), a selective inhibitor of cGMP-hydrolysing phosphodiesterase 5 (PDE5), which acts exclusively by increasing cGMP, can induce migraine and dilatation of cerebral arteries. We included 12 patients with migraine without aura in this double-blind, placebo-controlled crossover study, in which placebo or sildenafil 100 mg was administered orally on two separate days. Blood flow velocity in the middle cerebral artery (V(mca)) was recorded by transcranial Doppler ultrasonography and regional cerebral blood flow in the territory of the middle cerebral artery (rCBF(mca)) was measured using SPECT (single photon emission computed tomography) and xenon 133 inhalation. Radial and temporal artery diameters were studied using high-frequency ultrasonography. Headache response, tenderness of pericranial muscles, blood pressure and heart rate were measured repeatedly. We found that migraine attack was induced by sildenafil in 10 of 12 migraine patients and by placebo in two of 12 patients (P = 0.01). V(mca) (P = 0.1) and rCBF(mca) (P = 0.93) remained unchanged after sildenafil. Temporal (P = 0.47) and radial (P = 0.87) artery diameter and pericranial tenderness (P = 0.16) were unaffected by sildenafil. Systolic and diastolic blood pressures were unchanged but heart rate increased from a mean of 62 +/- 2 to 74 +/- 3 beats/min (P = 0.01) after sildenafil. Our results demonstrate that migraine may be induced via a cGMP-dependent mechanism, and we show for the first time that this occurs without initial dilatation of the middle cerebral artery. We propose that triggering mechanisms may reside within the perivascular sensory nerve terminals or the brainstem. However, other sites of action may also be possible and future studies are needed to elucidate this. In the clinical use of sildenafil, patients who have migraine should be informed about the risk of migraine attacks.
3',5'-Cyclic-GMP Phosphodiesterases↗
Migraine without aura and migraine with aura are distinct disorders. A population-based twin survey.
OBJECTIVE: To investigate the co-occurrence of migraine without aura (MWOA) and migraine with aura (MWA) in a population-based twin survey. BACKGROUND: Migraine without aura and MWA are multifactorial disorders. If MWOA and MWA share common genes, co-occurrence should be observed more frequently than expected, ie, the product of the prevalence in the general population. MATERIAL AND METHODS: The study population included all living Danish monozygotic (MZ) and same-gender dizygotic (DZ) twin pairs born between 1953 and 1960: 5360 twins (2026 MZ, 3334 DZ). The sample included 2840 men and 2520 women. All received a posted questionnaire, and those with possible migraine were interviewed via telephone by trained physicians (V.U. or M.G.). Twins who did not respond to the questionnaire and who had a co-twin with possible migraine were contacted by telephone. The questionnaire response rate was 87% (4660 of 5360), and the telephone interview was participated in by 90% (2035 of 2272). The physician interviewers were unaware of questionnaire answers, zygosity, and the clinical diagnosis of the co-twin. The criteria of the International Headache Society were used to establish a diagnosis of migraine. RESULTS: Lifetime prevalence in the twin sample: 7% of men and 19% of women had MWOA, while 7% of men and 8% of women had MWA. Lifetime prevalence of MWA in twin pairs with MWOA: MZ men, 2% (1 of 47); MZ women, 6% (5 of 90); DZ men, 9% (7 of 75); and DZ women, 10% (19 of 182). Lifetime prevalence of MWOA in twin pairs with MWA: MZ men, 3% (1 of 33); MZ women, 5% (3 of 58); DZ men, 9% (4 of 44); and DZ women, 13% (10 of 76). The observed and the expected numbers of twins with co-occurrence of MWOA and MWA based on the prevalence in the general population were not significantly different in either men or women (men, P=.1 and women, P=.5). CONCLUSION: The results strongly suggest that MWOA and MWA are distinct disorders, and identification of common genes for MWOA and MWA, thus, should not be expected to result from future genetic research.
Adult↗
The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow or blood velocity, but nevertheless induces headache in healthy subjects.
Cyclic nucleotides are important hemodynamic regulators in many tissues. Glyceryl trinitrate markedly dilates large cerebral arteries and increases cGMP. Here, the authors study the effect of sildenafil, a selective inhibitor of cGMP-hydrolyzing phosphodiesterase 5 on cerebral hemodynamics and headache induction. Ten healthy subjects were included in a double-blind, placebo-controlled crossover study where placebo or sildenafil 100 mg (highest therapeutic dose) were administered on two separate days. Blood velocity in the middle cerebral artery (Vmca) was recorded by transcranial Doppler, and regional cerebral blood flow in the perfusion area of the middle cerebral artery (rCBFmca) was measured using single photon emission computed tomography and xenon inhalation. Radial and temporal artery diameters were studied using high-frequency ultrasound. Blood pressure and heart rate were recorded repeatedly. Headache responses and tenderness of pericranial muscles were scored verbally. Sildenafil caused no significant changes in rCBFmca, Vmca, or in temporal or radial artery diameter, but heart rate increased and diastolic blood pressure decreased significantly compared to placebo. Despite the lack of cerebral arterial dilatation, sildenafil caused significantly more headache than placebo. The present results show that sildenafil 100 mg does not dilate cerebral or extracerebral arteries but nevertheless causes headache, which may be attributed to nonvascular mechanisms.
3',5'-Cyclic-GMP Phosphodiesterases↗
Muscle palpation with controlled finger pressure: new equipment for the study of tender myofascial tissues.
While manual palpation is the most important method for evaluation of tender myofascial tissues, it lacks reliability. Therefore, we have developed an instrument, called a 'palpometer', which allows the measurement of pressure exerted during palpation. The palpometer consists of a thin pressure-sensitive plastic device attached to the palpating finger, and of a scale recording the pressure applied to the device. Known forces were applied to the pressure sensitive device under various experimental conditions and the corresponding values were read on the palpometer scale. Then 14 observers, blinded to the palpometer scale, palpated the temporal muscle on the same subject twice, with an interval of 1 week. A highly significant correlation was found between palpometer recordings and forces applied to the pressure-sensitive device (P < 0.0001). Exerted force at a given palpometer value varied 3.1% within and 7.2% between 2 observers. During palpation of the temporal muscle pressure intensities within the 14 observers did not differ significantly from week to week (P = 0.68). Between the 14 observers pressure intensities varied considerably with a range of 73.5-196 arbitrary units. Thus, a reliable instrument for measuring pressure intensities during palpation of myofascial tissue has been developed. The large variation in palpation pressures between observers indicates that palpation of tender myofascial tissue may be considerably improved by use of the palpometer. This instrument will be indispensable in research studies employing palpation and in the training of physicians to diagnose myofascial pain disorders.
Adult↗
Muscle tenderness and pressure pain thresholds in headache. A population study.
Tenderness and pain thresholds in pericranial muscles were studied in a random sample of 735 adults aged 25-64 years. This study was a part of a multifaceted, epidemiological study of different headache disorders. Manual palpation and pressure pain threshold were performed by observers blinded to the persons' history of headache. The aim of the study was to evaluate the possible role of pericranial myofascial nociception in headache pathogenesis. Tenderness in migraineurs did not differ from non-migraineurs. Subjects with episodic tension-type headache and females with chronic tension-type headache were more tender than the rest of the population, and males without any experience of headache were less tender than the rest of the male population. A strong positive correlation between tenderness and frequency of tension-type headache was found (males: P < 10(-4); females: P < 10(-5)), while no relation between tenderness and migraine frequency was seen (P = 0.43). In subjects having actual headache at the day of examination tenderness was 32% increased compared to a matched group with identical usual frequency of headache, but without headache during the examination. A significant relation of tenderness to the recency of last episode of headache was detected in both sexes after control for usual frequency and actual headache (males: P < 10(-3); females: P < 10(-4)). Pressure pain thresholds were largely normal indicating normal pain processing and contradicting the idea that tension-type headache mainly is due to generally increased pain sensitivity. This study supports the pathogenetic importance of muscular factors in tension-type headache, while muscular factors are of no primary importance in migraine.
Adult↗
Cephalic muscle tenderness and pressure pain threshold in a general population.
Tenderness and pain thresholds in pericranial muscles were studied in a general population. A random sample of 1000 adults aged 25-64 years was drawn as part of the Glostrup Population Studies, and 740 adults were examined. This study was part of a multifacetted, epidemiological study of different headache disorders according to the new headache classification. Manual palpation and pressure pain threshold with an electronic pressure algometer were performed by observers blinded to other information such as the person's history of headache, previous illness and mental state. The muscles most commonly tender to manual palpation were the lateral pterygoid (55%), the trapezius (52%), and the sternocleido-mastoid muscles (51%). Females were more tender than men in all the muscles examined by manual palpation. In total, the young age group was more tender than the old age group (P = 0.03). Pressure pain thresholds on temporal muscles showed lower thresholds in women than in men (P less than 10(-3)), and in the total population thresholds increased with age (P less than 0.05). No side-to-side difference in tenderness by manual palpation was found, while the right side showed increased pain thresholds in right-handed individuals (P less than 10(-4)). No side-to-side difference was found in left-handed persons. This study provides data about the normal population and forms the necessary basis for evaluating the importance of muscle tenderness in headache subjects and other selected groups.
Adult↗
Plasma and cerebrospinal fluid beta-endorphin in chronic tension-type headache.
Previous studies have provided evidence of an increased sensitivity to pain, a decreased hypothalamic opioid tone, and decreased cerebrospinal fluid (CSF) beta-endorphin (beta-EP) concentration in patients with primary chronic headache. We applied separate specific radioimmunoassays for beta-EP in CSF and plasma on samples from age-matched controls and a group of 50 patients with chronic tension-type headache (CTH) fulfilling the diagnostic criteria set by the International Headache Society. Median CSF beta-EP concentrations (95% confidence limits) were 12.8 pmol/l (11.0-14.5) in CTH patients and 11.9 pmol/l (10.9-14.2) in the control group, which is not significantly different (P = 0.28). Plasma beta-EP concentrations did not differ either, being 3.1 pmol/l (2.4-3.7) and 3.3 pmol/l (1.8-4.0) in the patients with CTH and in controls, respectively (P = 0.88). Plasma and CSF beta-EP concentrations did not correlate. Reversed-phase high performance liquid chromatography (HPLC) of CSF pools from the headache patients and controls revealed similar profiles of beta-EP-immunoreactivity both when C-terminally and N-terminally directed antisera were used, suggesting a normal post-translational processing of the pro-opiomelanocortin gene in patients with CTH. beta-EP is not involved in the pathogenesis of CTH, or such a role is not reflected in CSF or plasma concentrations of the neuropeptide.
Adult↗
Getting away from simple muscle contraction as a mechanism of tension-type headache.
Explore the source record for details and available documents.
Headache↗
Clinical and pathophysiological observations in migraine and tension-type headache explained by integration of vascular, supraspinal and myofascial inputs.
A vascular-supraspinal-myogenic (VSM) model for pain in migraine based on our previous clinical and pathophysiological observations is proposed. According to the model, perceived pain (headache) intensity is determined by the sum of nociception from cephalic arteries and pericranial myofascial tissues converging upon the same neurons and integrated with supraspinal effects (usually facilitating). Vascular input predominates over myofascial input in migraine, whereas significance of supraspinal facilitation is difficult to estimate. The importance of these 3 effects may vary between patients and in the same individual with time. The model is in accordance with recent experimental studies showing convergence of somatovisceral afferents upon n. caudalis neurons. Also, long term potentiation due to nociceptive activation and sensitization of neurons to input from wider areas and non-nociceptive stimuli are relevant to our model. In tension-type headache, nociception is primarily myofascial, but vascular input cannot be disregarded. Supraspinal facilitation probably plays a large, sometimes dominant role (the MSV model). The model explains much of the complexity of the clinical picture of these disorders as well as their tendency to overlap and to change into one another. Also, a number of pathophysiological observations such as why muscles are tender during migraine, why trigger-point injection may cure migraine attacks and why chronic tension-type headache is often associated with episodes of pulsating pain, can be explained. The model gives a rational explanation of empirically developed, internationally accepted, multimodal treatment strategies for migraine and tension-type headache. It may thus serve a useful purpose in explaining the disorder to patients. Finally, the model points to several avenues of future research in animals and man.
Animals↗
Intravenous nitroglycerin as an experimental model of vascular headache. Basic characteristics.
To develop a reliable experimental model of vascular headache, we studied the dose-response relationship between headache and i.v. nitroglycerin (NTG) in 10 healthy subjects. NTG was infused intravenously over periods of 10 min separated by wash-out periods. Doses of 0.25, 0.50, 1.00 and 2.00 micrograms/kg/min were applied successively with one placebo infusion and wash-out period inserted randomly and double blindly. The subjects scored their headache intensity on a scale 0-10. After 1-8 weeks a retest was performed. Nine subjects developed headache already at 0.25 microgram/kg/min, whereas one had no headache at any dose. Headache severity did not increase with doses above 0.5 microgram/kg/min. This ceiling effect was reproducible. The headache was moderate, usually throbbing, bifrontal and not associated with other migrainous features. It reached maximum within 2.5-5.5 min (medians) at various doses and declined rapidly after NTG discontinuation. Wash-out periods of 10-20 min were sufficient. The reproducibility of headache intensity and character was satisfactory in the retest experiment. There were no unpleasant side effects and no visible flushing. Thus blindness was maintained. I.v. NTG is suitable as an experimental headache model. A constant infusion of 0.5 microgram/kg/min will be suitable for studies of arterial diameter, pulsations, blood flow, etc. Comparative studies of sensitivity should use the present infusion schedule but with the two highest doses substituted by 0.06 and 0.125 microgram/kg/min.
Adult↗
Pericranial muscle tenderness and pressure-pain threshold in the temporal region during common migraine.
Twenty-six patients were examined during attacks of common migraine as well as during headache-free interval. Pericranial tenderness was scored blindly by a systematic manual palpation on both occasions by the same observer. Pressure-pain threshold (PPT) in a fixed location over the temporal muscle was determined by the use of a pressure algometer. A 28% increase in total tenderness score was observed during attacks (P less than 0.01). During unilateral attacks, tenderness scores were significantly higher on the ipsilateral side as compared to the contralateral (P less than 0.01). A positive correlation was observed between tenderness on the two sides (P less than 0.05) and the two occasions (P less than 0.01). PPT showed no changes during migraine attacks and there was no difference in PPT between the ipsilateral and contralateral side. A positive correlation was observed between PPT on the two sides and the two occasions (P less than 0.01). PPT was not correlated to the tenderness scores obtained by manual palpation. The absence of a decrease in PPT and the presence of several tender areas in multiple regions, particularly where pain was spontaneously reported to be located, suggest the presence of either a multi-focal peripheral pathological process or referred pain from other structures in the head and neck region.
Adult↗
Peptide-containing nerve fibres in human extracranial tissue: a morphological basis for neuropeptide involvement in extracranial pain?
It has been suggested that a number of peptides may be involved in the transmission of pain. In order to evaluate the possible role of peptides in the development of headache, we have, in the present study, examined the presence of nerve fibres containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) in human temporal and occipital tissues. In the skin, delicate VIP, SP and CGRP fibres occur beneath the epidermis, sometimes running into the folds of the dermal ridges. In deeper layers of the dermis, small blood vessels are occasionally surrounded by single nerve fibres containing NPY, VIP, SP and CGRP. Large temporal and occipital arteries are surrounded by a meshwork of such fibres. In addition, NPY and VIP fibres are seen around sweat glands and hair follicles. Smooth muscle bundles in the dermis are surrounded by VIP fibres, whereas the temporal muscle per se is devoid of such fibres.
Calcitonin Gene-Related Peptide↗
Pressure-pain threshold in human temporal region. Evaluation of a new pressure algometer.
A hand-held pressure algometer with a pressure sensitive strain gauge at the tip was used to measure the pressure-pain threshold (PPT) in the temporal region of healthy volunteers. Various sizes of circular tips and various application rates were tested before selecting an area of 0.5 cm2 and a constant application rate of 0.68 N X sec-1 for future use. A highly significant correlation was found between PPT values obtained from the two sides (of the head) (P less than 0.001) and between PPT values obtained with a 3-week interval (P less than 0.001). In a series of 50 immediate consecutive measurements in the same individual, the mean PPT was 171 kPa (N = 6, 2 S.D. 24%). The mean relative change in PPT after a 3-week interval was 0 +/- 51% (N = 11, 2 S.D.). In the course of 5 repeated determinations at weekly intervals there was a significant increase in PPT (ANOVA, P less than 0.05). Subcutaneous lignocaine significantly elevated PPT compared to placebo. Due to the high inter-individual variation, determinations of PPT for group comparisons should include rather large population samples, whereas in paired studies, the intra-individual variation allows the investigation of much smaller groups (10-20 subjects). It is our experience that the pressure algometer is easy to operate in the hands of a skilled laboratory assistant.
Adult↗
Drug abuse in migraine patients.
Records of all patients discharged with a diagnosis of migraine from 2 Danish neurological departments were examined to determine the incidence of drug abuse. These departments had fixed uptake areas with a population of approximately 500,000 during the 5 year study period (1-1-1976--31-12-1980). Patients were selected for detailed analysis if (1) they used morphinomimetic drugs once a month or more, (2) took 7 or more tablets of weak analgesics a day or (3) consumed more than 60 mg ergotamine a month. A total of 92 patients fulfilled these criteria, 27 only because of ergotamine overuse. Injections of morphinomimetic drugs were given once a week or more frequently to 32 patients. These patients also usually had an escalating consumption and were usually regarded as abusers by their doctors. During admission morphinomimetics were discontinued. None deteriorated, 1/3 remained unchanged whereas 2/3 improved. Thus 32 patients can be regarded as abusers of morphinomimetics which represents an annual incidence of 13 per million inhabitants. We caution against the use of morphinomimetics in migraine.
Adult↗