beta-endorphin and Migraine-Disorders

The biochemistry of migraine is complex. Many contradictory or never replicated findings in often small patient groups have been published. The following observations in the platelet-free plasma and urine appear to have some solid basis and will be discussed: 1) systemic derangement of 5-HT metabolism, relevant to the peripheral vascular component of migraine pathophysiology, 2) changes in neuroexcitatory amino acids and magnesium, which may reflect a predisposition of the migraine patient, notably those having attacks with aura, to develop spreading depression, 3) alterations in methionine-enkephalin levels, which may be a useful marker to discriminate between tension headache and migraine, 4) hormonal fluctuations which seem important to set the threshold for an attack, 5) changes of vasoactive peptides in the cranio-vascular circulation, providing the first human evidence that the trigemino-vascular system indeed is relevant in migraine, and 6) catecholaminergic changes suggesting sympathetic overactivity. Finally distinct biochemical differences between patients with migraine without aura and patients with tension headache on one hand, and between patients with migraine with aura and patients with migraine without aura on the other hand will be emphasized. Findings in platelets will be discussed only if they are complementary and supportive to the plasma and urine data.

Topics: Aspartic Acid; beta-Endorphin; Catecholamines; Enkephalin, Methionine; Estrogens; Female; Glutamates; Humans; Hydroxyindoleacetic Acid; Male; Migraine Disorders; Neuropeptides; Serotonin

To explore the cause and pathogenesis of migraine based on TCM theory and modern researches to seek for new thinking and effective drugs in treating migraine.. Ninety patients with migraine were divided into three groups, the treated group treated with Shutianing Granule (STNG) 9 g, three times a day, the control A group treated with composite Yangjiao capsule, 5 capsules each time, three times a day and the control B group treated with flunarizine hydrochloride capsule, 5 mg, once a day. The treatment lasted for 28 days to observe the degree, lasting time and frequency of pain attack, and the headache index was calculated. Transcranial Doppler examination, serum beta evoked potential (beta-EP) and neuropeptide (NPY) determination were also performed before and after treatment. In the experimental study, effect of treatment of cerebral NPY and beta-EP were tested in SD rats with chronic pain in the treated or the control groups.. In the treated group, the markedly effective rate was 56.67% and the total effective rate was 90.00%, significant difference was shown in comparison with those in the control B group (P < 0.05), but with no difference in comparison with those in the control A group. Cerebral beta-EP level was raised and plasma NPY level was lowered in all the three treated groups. Compared with the normal saline group, there was significant difference (P < 0.05 or P < 0.01).. STNG could improve the cerebrovascular function effectively, raise plasma beta-EP level, lower plasma NPY level and alleviate vascular tension in patients with migraine.

Topics: Adult; Animals; beta-Endorphin; Drugs, Chinese Herbal; Female; Humans; Male; Middle Aged; Migraine Disorders; Neuropeptide Y; Phytotherapy; Random Allocation; Rats; Rats, Sprague-Dawley

We investigated the effectiveness of acupuncture in childhood migraine in 22 children with migraine, randomly divided into two groups: a true acupuncture group (12 children) and a placebo acupuncture group (10 children). Ten healthy children served as a control group. Opioid activity in blood plasma was assayed by two methods: (1) determination of total (panopioid) activity with an opiate radioreceptor assay, and (2) determination of beta-endorphinlike immunoreactivity by radioimmunoassay. The true acupuncture treatment led to significant clinical reduction in both migraine frequency and intensity. At the beginning of the study, significantly greater panopioid activity was evident in plasma of the control group than in plasma of the migraine group. The true acupuncture group showed a gradual increase in the panopioid activity in plasma, which correlated with the clinical improvement. After the tenth treatment, the values of opioid activity of the true acupuncture group were similar to those of the control group, whereas the plasma of the placebo acupuncture group exhibited insignificant changes in plasma panopioid activity. In addition, a significant increase in beta-endorphin levels was observed in the migraine patients who were treated in the true acupuncture group as compared with the values before treatment or with the values of the placebo acupuncture group. The results suggest that acupuncture may be an effective treatment in children with migraine headaches and that it leads to an increase in activity of the opioidergic system.

Topics: Acupuncture Therapy; Adolescent; beta-Endorphin; Child; Female; Humans; Male; Migraine Disorders; Opioid Peptides; Receptors, Opioid; Treatment Outcome

Interictal serum levels of serotonin and plasma and mononuclear cell concentrations of beta-endorphin were measured in 20 juvenile patients (13 suffering from migraine without aura and 7 from episodic tension-type headache) before and after 3 months of L-5-hydroxytryptophan treatment (5 mg/kg/day) and compared with a control group of 17 headache-free healthy subjects. While no significant differences in serum serotonin levels emerged between the three groups (migraine 104.6 +/- 26 micrograms/L, tension-type headache 90.7 +/- 26.2 micrograms/L, controls 96 +/- 32.9 micrograms/L), significantly lower plasma and mononuclear cell concentrations of beta-endorphin were found in both patient groups by comparison with the healthy controls (beta-endorphin in plasma: migraine sufferers 16.2 +/- 4.2 pmol/L [P < 0.05], tension-type headache subjects 14.5 +/- 1.7 pmol/L [P < 0.001] vs controls 21.3 +/- 4.6 pmol/L and respectively, beta-endorphin in mononuclear cells: migraine sufferers 110.5 +/- 16.4 pmol/10(6) GB/L [P < 0.001], tension-type headache subjects 142.3 +/- 22.7 pmol/10(6) GB/L [P < 0.001] vs controls 359.3 +/- 31.6 pmol/10(6) GB/L). No differences emerged between the two clinical forms of headache for the plasma and mononuclear cell concentrations of beta-endorphin. After L-5-hydroxytryptophan treatment, serum serotonin and both plasma and mononuclear cell beta-endorphin levels tended to be higher, though not significantly so, than prior to treatment, and the clinical score (frequency x intensity of headache attacks) was significantly lower in both headache groups than at the baseline. This study supports the theory that opiate analgesic system function is abnormally low in juvenile primary headache as in adults, and confirms that administering serotoninergic precursor drugs increases beta-endorphin, even in the peripheral blood, and may favorably affect clinical symptoms.

Topics: 5-Hydroxytryptophan; Adolescent; Adult; beta-Endorphin; Child; Female; Headache; Humans; Male; Migraine Disorders; Monocytes; Serotonin; Tension-Type Headache

To observe the effects of moxibustion at "Baihui" (GV 20) and "Dazhui" (GV 14) at different time points on the serum level of β-endorphin (β-EP), substance P (SP) and expression of interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) protein in brainstem in rats with migraine, and to explore the effect and mechanism of moxibustion in preventing and treating migraine.. Forty male SD rats were randomly divided into a blank group, a model group, a prevention+treatment (PT) group and a treatment group, 10 rats in each group. Except the blank group, the rats in the remaining groups were injected with nitroglycerin subcutaneously to prepare migraine model. The rats in the PT group were treated with moxibustion 7 days before modeling (once a day) and 30 min after modeling, while the rats in the treatment group were treated with moxibustion 30 min after modeling. The "Baihui" (GV 20) and "Dazhui" (GV 14) were taken for 30 minutes each time. The behavioral scores in each group were observed before and after modeling. After intervention, ELISA method was used to detect the serum level of β-EP and SP; the immunohistochemistry method was used to detect the number of positive cells of IL-1β in brainstem; the Western blot method was used to detect the expression of COX-2 protein in brainstem.. Compared with the blank group, the behavioral scores in the model group were increased 0-30 min, 60-90 min and 90-120 min after modeling (. Moxibustion could effectively relieve migraine. The mechanism may be related to reduce the serum level of SP, IL-1β and COX-2 protein expression in brainstem, and increase the serum level of β-EP, and the optimal effect is observed in the PT group.

Topics: Animals; beta-Endorphin; Brain Stem; Cyclooxygenase 2; Interleukin-1beta; Male; Migraine Disorders; Moxibustion; Rats; Rats, Sprague-Dawley; Substance P

To study the effect of Qilongtoutong granule (QLTT) on plasma calcitonin gene-related peptide (CGRP), beta-endorphin (beta-EP), 5-HT, dopamine (DA), noradrenalin (NE), and blood viscosity in migraine model rats and mice.. Both the acute blood stasis model group and nitroglycerin-induced migraine model group included 60 Sprague-Dawley rats. The reserpine-reduced model group had 60 Kunming mice. Rats from each test were grouped into normal control group, model group, Zhengtian pill (ZTP) group, and high, moderate, or low-dose QLTT groups. In the acute blood stasis model test, after gavage for 7 days, rats were given 0.8 mL/kg adrenaline hydrochloride subcutaneously twice, and kept in ice water for 5 min. After fasting for 12 h, rats were anesthetized and blood samples were collected for detection of blood viscosity. In the nitroglycerin-induced migraine group, after gavage for 7 days, rats were intraperitoneally injected nitroglycerin (10 mg/kg), and 4 h later, blood samples were collected from postcava for measuring the plasma CGRP and beta-EP levels. In the reserpine-reduced model test, except the normal control group, mice were administered reserpine (0.25 mg/ kg, i.h.) for 9 days. Mice received intragastric administration from the third day to the ninth day. One hour after the last gavage, blood and brain tissue samples were obtained. Then, blood clotting time and the contents of neurotransmitters were determined.. QLTT- (3.6, 1.8, and 0.9 g/kg) and ZTP-treated rats had lower blood viscosity than that in model rats under different shear rates (P < 0.01). QLTT- (3.6, 1.8 g/kg) and ZTP-treated rats had significantly lower plasma CGRP levels and higher plasma beta-EP levels than those in model rats (P < 0.01). QLTT treatment at dose of 0.9 g/kg had lower plasma CGRP levels as well (P < 0.05). QLTT- (5.2, 2.6 g/kg) and ZTP-treated mice had longer blood clotting time than that in model mice (P < 0.01). QLTT- (2.6 g/kg) and ZTP-treated mice had higher plasma serotonin (5-HT) levels than those in model mice (P < 0.05).. QLTT-treated animals had lower plasma CGRP level, higher plasma beta-EP, 5-HT, higher brain tissue 5-HT, NE, DA levels, and lower blood viscosity than those in the migraine model animals.

Topics: Animals; beta-Endorphin; Calcitonin Gene-Related Peptide; Disease Models, Animal; Dopamine; Drugs, Chinese Herbal; Female; Humans; Male; Mice; Migraine Disorders; Norepinephrine; Rats; Rats, Sprague-Dawley; Serotonin

Low β endorphin level in serum and cerebrospinal fluid (CSF) has been reported in migraine. The basis of pain relief in migraine by repetitive transcranial magnetic stimulation (rTMS) may be related to β endorphin (BE), which has not been evaluated. It is proposed to measure plasma β endorphin level in migraine patients and the change in β endorphin level following rTMS, and to correlate these changes with migraine relief.. Twenty-five patients with migraine diagnosed as per International Headache Society criteria and 20 gender- and age-matched controls were included. Their clinical characteristics including duration of migraine, its frequency, severity and functional disability, triggers, allodynia and number of analgesic used were noted. Plasma β endorphin level was estimated before and after the third rTMS session. rTMS was delivered on the hot spot of right abductor digiti minimi on alternate days for 3 days and each session consisted of 600 pulses at 10 Hz. The clinical response was noted weekly for 1 month and correlated with β endorphin level.. The median age of the patients was 35 (20-50) years and 19 were females. Eight patients had episodic and 17 chronic migraine. β endorphin level was significantly lower in migraine (4.35 ± 2.29 ng/ml) compared to controls (6.68 ± 2.93 ng/ml). β endorphin level was lower in chronic compared to episodic migraine (3.74 ± 2.20 versus 5.65 ± 2.02 ng/ml). Following rTMS, the headache frequency, severity, functional disability and analgesic intake significantly reduced on the seventh day of rTMS and remained significant until the fourth week compared to the baseline. The clinical improvement was associated with increase in β endorphin level (4.35 ± 2.29 versus 6.58 ± 3.33 ng/ml).. It can be concluded from this study that the basal plasma β endorphin level was low in migraine patients, especially in chronic migraine. The improvement in migraine after rTMS was associated with increase in β endorphin level.

Topics: Adult; beta-Endorphin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Migraine Disorders; Transcranial Magnetic Stimulation; Treatment Outcome; Young Adult

Levels of beta-endorphin in peripheral blood mononuclear cells have been studied as a new approach to investigating opioid tone in migraine and tension-type headache. Sixty-one patients with migraine without aura, 39 with migraine with aura and 23 with episodic tension-type headache were compared with 37 healthy controls. Peripheral blood samples were taken from patients not enduring headache attacks and not undergoing prophylactic treatment. A significant reduction in peripheral blood mononuclear cell beta-endorphin concentrations was observed in migraine patients with and without aura, but not in tension-type headache patients. Altered transmitter modulation to peripheral blood mononuclear cells may be the cause of this alteration, which could be part of a more diffuse opioid system derangement in migraine subjects.

Topics: Adult; beta-Endorphin; Female; Headache; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Migraine Disorders; Radioimmunoassay

The somatostatin-like (SLI), the neuropeptide Y-like (NPY-LI), and the beta-endorphin-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.

Topics: Adult; beta-Endorphin; Female; Humans; Male; Middle Aged; Migraine Disorders; Neuropeptide Y; Radioimmunoassay; Somatostatin

Topics: beta-Endorphin; Humans; Leukocytes, Mononuclear; Migraine Disorders

Alpha-N-acetyl-beta-endorphin (Ac-beta-EP) is a post-translational product of beta-endorphin (beta-EP) with no analgesic properties. Ac beta-EP is present in human fetal and adult pituitary gland and cross-reacts in all available beta-EP assays. This study evaluates levels of Ac-beta-EP in the cerebrospinal fluid (CSF) of 22 normal subjects and 15 chronic headache sufferers. Since dopamine may play a role in the acetylation process, homovanillic acid levels were also determined. After extraction and high performance liquid chromatographic (HPLC) fractionation of CSF, an immunoreactive Ac-beta-EP peak was detected coeluting with reference peptide. Ac-beta-EP was detectable in all but 5 normal subjects. In headache sufferers, Ac-beta-EP levels were always detectable and their mean value was significantly higher than that of healthy subjects (11.6 +/- 11.8 vs 3.9 +/- 3.6 fmol/ml; P less than 0.01). Conversely, CSF beta-endorphin (beta-EP) concentrations were decreased in headache patients (9.8 +/- 9.4 vs 15.7 +/- 9.7 fmol/ml; P less than 0.05), and as a consequence the beta-EP/Ac-beta-EP ratio was also markedly reduced (P less than 0.005). No difference was observed for CSF homovanillic acid concentrations. These data demonstrate that HPLC coupled to radioimmunoassay allows the identification of low but significant amounts of Ac beta-EP in human CSF. This compound represents a confounding factor when beta-EP immunoreactivity is assessed by conventional methods. In headache sufferers, Ac-beta-EP levels were higher than normal, whereas beta-EP concentrations were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; beta-Endorphin; Chromatography, High Pressure Liquid; Chronic Disease; Female; Headache; Homovanillic Acid; Humans; Male; Middle Aged; Migraine Disorders; Muscle Contraction; Pain; Radioimmunoassay; Reference Values

Tumor Necrosis Factor-alpha/cachectin (TNF-alpha/cachectin), Lipopolysaccharide (LPS), ACTH, beta-Endorphin (beta-EPH), and Cortisol (F) levels were determined in 33 Headache patients: 22 patients were affected with Migraine (M) and 11 patients with Chronic Type Tension Headache (CTTH). TNF-alpha/cachectin serum level was detected in 15 out of 22 migraneous patients and in no CTTH patients. Plasma LPS was observed in 11 out of 15 TNF-alpha/cachectin positive migraneous patients (73%) and in 3 out of 11 CTTH patients (27%). A negative correlation was observed between TNF-alpha/cachectin values and either ACTH or beta-EPH. In the group of migraneous patients the presence of serum TNF-alpha/cachectin showed a sensibility of .6 and a specificity of 1. The endocrine and immunological implications concerning these data are discussed.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Chronic Disease; Endotoxins; Female; Headache; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Limulus Test; Male; Middle Aged; Migraine Disorders; Pituitary-Adrenal System; Tumor Necrosis Factor-alpha

In this study we measured concentrations of beta-endorphin, ACTH, prolactin and cortisol in plasma of migraine patients (ages 10-19) and age-matched controls, and the effects of behaviour therapy on both migraine and the endocrine parameters. Two groups of migraine patients (M) and controls (C) were recruited: group I (MI, n = 11; CI, n = 13) in winter and group II (MII, n = 9; CII, n = 7) in summer. Both M groups received behaviour therapy: group MI immediately and group MII after a waiting period of 3.5 months. Hormone determinations were made before and after the behaviour therapy of group MI and before and after the waiting period of group MII. At the first measurement (before therapy and waiting period), migraine subjects had lower concentrations of beta-endorphin than controls. After behaviour therapy, both groups showed a significant decline in migraine, which was retained at follow-up 9-12 months after completion of the therapy. Improvement of migraine after behaviour therapy was accompanied by a rise in the level of beta-endorphin in group MI. In contrast, the patients of the waiting period (group MII) showed improvement in migraine after the waiting period but no changes in beta-endorphin. Seasonal differences were observed for beta-endorphin, prolactin and cortisol, winter values being lower than summer values.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Behavior Therapy; beta-Endorphin; Child; Female; Humans; Hydrocortisone; Male; Migraine Disorders; Prolactin

Thanks to recent biochemical and neuroendocrine findings, migraine belonging to the group of primary headaches appears as a pathology of the antinociceptive system with evolutive character. It has been demonstrated, in fact, that right at the early stage of migraine, there is a significant reduction in liquoral concentrations of beta-endorphin (beta-E), endogenous opioid peptide followed by a similar change in the plasma opioid system. The opioid system deficiency is even more evident after stimulation tests that point to reduced reactivity of the hypothalamo-hypophyseal system with respect to stimuli that in normal subjects trigger hypophyseal beta-E incretion. Caffeine, a member of the methyl-xanthine group, is an interesting molecule in the study of migraine patients because the chronic intake of this substance, contained in numerous analgesics, has been related to the chronic nature of the pain. The purpose of the present study is to assess the relationship between caffeine consumption and plasma opioid system. With the administration of a single oral dose of caffeine, normal subjects present an increase in plasma concentrations of beta-E, while in patients with chronic migraine, the response is significantly lower. These data confirm the poor reactivity of the plasma opioid system to pharmacological stimuli in migraine. Average daily consumption of caffeine has also been determined. It was not possible to establish a correlation between consumption of caffeine and plasma concentrations of beta-E whether basal or after stimulus with caffeine.

Topics: Administration, Oral; Adult; beta-Endorphin; Caffeine; Chronic Disease; Female; Humans; Male; Middle Aged; Migraine Disorders

Blood plasma beta-endorphin concentrations were measured in 87 patients with various facial and head pain syndromes: trigeminal neuralgia or neuropathy Horner syndrome and migraine, facial autonomic pains. beta-endorphin concentrations were measured before and after treatment. In the groups under investigation, the neuropeptide showed opposite changes in plasma levels after the therapy depending on the type of the syndrome.

Topics: Adult; beta-Endorphin; Cluster Headache; Female; Humans; Male; Middle Aged; Migraine Disorders; Trigeminal Neuralgia; Vascular Headaches

In this study the 24-h pattern of blood pressure (BP), heart rate (HR), plasma catecholamine (CA), beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and RIII threshold was investigated in a patient suffering from chronic paroxysmal hemicrania (CPH). The investigation was carried out before and during indomethacin therapy in order to assess the presence or otherwise of a disordered biorhythmic organization resembling that documented in cluster headache (CH). A severe alteration in the majority of the rhythms explored was found not only during the drug-free phase, but also in the indomethacin phase of the investigation. These data are similar to those obtained in CH studies and point to the possibility of a common pathophysiological mechanism.

Topics: Adult; beta-Endorphin; beta-Lipotropin; Blood Pressure; Catecholamines; Chronic Disease; Circadian Rhythm; Female; Hemodynamics; Humans; Indomethacin; Migraine Disorders

Migraine is a psychobiological disorder in which a recurrent failure of opioid and adrenergic systems might occur, as plasma and CSF studies suggest. In order to elucidate the relationship between noradrenergic and opioidergic functions, the plasma beta-endorphin (beta-EP) response to clonidine and the cortisol response to dexamethasone were evaluated together in 25 patients suffering from migraine without aura, and with chronic tension headache (MTH). Baseline beta-EP plasma levels and beta-EP response to clonidine were significantly lower in MTH subjects than in controls, suggesting a postsynaptic hypothalamo-pituitary impairment. Forty-four percent of the MTH subjects showed either a lack of suppression of plasma cortisol following dexamethasone administration, or basal cortisol concentrations higher than controls and suppressors, suggesting a disinhibition of the hypothalamopituitary-adrenal (HPA) axis. An inverse correlation was found between pain severity and beta-EP secretion induced by clonidine (delta max), and no relationship was found between beta-EP and mood. These data suggest a failure of central noradrenergic activity, or perhaps an impaired secretion of beta-EP not related to HPA axis hyperactivity or to affective state.

Topics: Adult; beta-Endorphin; Clonidine; Dexamethasone; Female; Headache; Humans; Hydrocortisone; Male; Middle Aged; Migraine Disorders; Receptors, Adrenergic, alpha

In this study we have examined the results of salmon calcitonin treatment on migraine pain. The mechanism by which calcitonin induces analgesia is still not understood. We observed the effect of a 5-day treatment with salmon calcitonin (IM 100 IU/day) on circulating levels of beta-endorphin, ACTH, and cortisol in 20 patients with migraine during the headache-free period. All 3 hormones were increased after the calcitonin administration and the maximum increase was obtained in beta-endorphin levels. There were significant statistical correlations between beta-endorphin, ACTH, and cortisol levels determined before and after calcitonin treatment.

Topics: Adrenocorticotropic Hormone; Adult; Animals; beta-Endorphin; Calcitonin; Female; Humans; Hydrocortisone; Male; Middle Aged; Migraine Disorders; Reference Values; Salmon

Endogenous opioid peptides, by modulating the release of sympathetic transmitters, may play a role in the pathogenesis of migraine and related headaches which are considered hypernociceptive syndromes. Hypoendorphinaemia has been demonstrated in migraine attack. Captopril, a drug able to potentiate morphine analgesia in rats and inhibit enkephalinase in animals and in man, improves the clinical course of migraine. In the present research the cerebrospinal fluid and plasma beta-endorphin (beta-EP) levels have been evaluated following a single oral dose of captopril. The drug increased plasma beta-EP levels in migraine sufferers, and these data may be relevant in the mechanism of action of this drug in migraine and related headaches.

Topics: beta-Endorphin; Captopril; Endorphins; Headache; Humans; Migraine Disorders

L-Tryptophan (L-TP) has been used in migraine and other pain conditions. The mechanism underlying the analgesic effect is still partly undefined. In this study the effects of subchronic administration of L-5-hydroxytryptophan (L-5HTP) (with and without carbidopa) on plasma beta-endorphin (beta-EP) levels and subjective pain threshold and tolerance were investigated in seven healthy volunteers. To measure also an objective indicator of pain, the nociceptive flexion reflex threshold was studied. L-5HTP treatment with and without carbidopa administration increased beta-EP levels significantly (p less than 0.05). L-5HTP plus carbidopa induced an increase in beta-EP significantly (p less than 0.05) greater than that induced by L-5HTP alone. Neither the subjective pain threshold and tolerance nor the RIII threshold was modified by either treatment. Our data seem to point to the existence of a complex linkage between plasma opioid levels and pain perception.

Topics: Adult; beta-Endorphin; Carbidopa; Drug Therapy, Combination; Endorphins; Humans; Migraine Disorders; Pain; Sensory Thresholds; Tryptophan

L-Tryptophan (L-TP) has been used in migraine and other pain conditions. The mechanism underlying the analgesic effect is still partly undefined. In this study the effects of subchronic administration of L-5-hydroxy-tryptophan (L-5HTP) (with and without carbidopa) on plasma beta-endorphin (beta-EP) levels and subjective pain threshold and tolerance were investigated in seven healthy volunteers. To measure also an objective indicator for pain, the nociceptive flexion reflex threshold was studied. L-5HTP treatment with and without carbidopa administration increased beta-EP levels significantly (p less than 0.05). L-5HTP plus carbidopa induced an increase in beta-EP significantly (p less than 0.05) higher than that after L-5HTP alone. Neither subjective pain threshold and tolerance nor RIII threshold was modified by either treatment. Our data seem to point to the existence of a complex linkage between plasma opioid levels and pain perception.

Topics: 5-Hydroxytryptophan; Adult; beta-Endorphin; Carbidopa; Drug Therapy, Combination; Endorphins; Humans; Migraine Disorders; Pain; Sensory Thresholds

The authors reviewed the connection between sexual hormones and migraine crisis. Besides other exogenous factors, the fall of estradiol blood levels in the late luteal and premenstrual phase seems a causal factor in the origin of menstrual-related headache crisis. The behaviour of migraine crisis during the various events of female reproductive life, support this view. The role of PRL, T, FSH and LH was also discussed. On the other hand, menstrual migraine represents a model that fits perfectly with a neuroendocrine hypothesis which is based upon a faulty chronobiological response of the so-called antinociceptive system.. The authors reviewed the connection between sex hormones and migraine crisis. Besides other exogenous factors, the fall in estradiol blood levels during the late luteal and premenstrual phase seems a causal factor in the origin of menstrual-related headaches. The behavior of migraine crisis during the various events of the female reproductive period support this view. The role of prolactin, follicle stimulating hormone, testosterone, and luteinizing hormone were also discussed. At the same time, menstrual migraine represents a model that fits perfectly with a neuroendocrine hypothesis which is based on a faulty chronobiological response of the so-called antinociceptive system.

Topics: beta-Endorphin; beta-Lipotropin; Contraceptives, Oral, Combined; Endorphins; Estrogens; Female; Humans; Menopause; Menstrual Cycle; Migraine Disorders; Pregnancy; Progesterone

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Endorphins; Female; Headache; Humans; Male; Middle Aged; Migraine Disorders; Vascular Headaches

The role of opioid peptides in modulating the nervous system adaptability has been demonstrated recently; proopiomelanocortin (POMC)-related peptides, in particular, serve in pain perception, in adaptation to stress, and in modulating higher brain functions. Primary headaches, besides pain, involve neuroendocrine/autonomic/adaptive processes as well as mood and personality factors. The view that primary headaches can be taken as a possible model of POMC-related peptides dysfunction led us to evaluate the resting plasma and CSF peptide levels and their plasma changes in response to various stimuli affecting their release. The data obtained from basal and dynamic studies agree with the concept that primary headaches are sustained by opioid system disturbance. In particular the reduced release of endogenous opioids by anterior pituitary in response to physical, endocrine or pharmacological stimuli agrees with a weak adaptive ability of headache sufferers. This impairment of endorphin responsiveness could play a key role in headache susceptibility to environmental stimuli. Primary headaches constitute a wide, intriguing field, including several subgroups bordering on "ischemic" and behavioral/affective disorders. The development of neuroendocrine techniques could be a useful means for supporting the clinical criteria identifying subpopulations of headache sufferers.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Chronic Disease; Clonidine; Cluster Headache; Dexamethasone; Endorphins; Headache; Humans; Hydrocortisone; Middle Aged; Migraine Disorders; Pro-Opiomelanocortin

Plasma levels of beta-endorphin and ACTH were measured during and outside migraine attacks in 17 patients with common migraine and 11 patients with classic migraine. Specific radioimmunoassays for beta-endorphin and ACTH were used. The beta-endorphin assay did not cross-react with beta-lipotropin. In common migraine, median plasma beta-endorphin was 3.3 pmol/l (95% confidence limits: 2.5-4.0 pmol/l) during attacks and 2.9 (2.4-3.2) pmol/l in the headache-free period. In classic migraine, plasma beta-endorphin was 3.2 (1.4-4.3) pmol/l during attacks and 2.4 (1.1-3.6) pmol/l outside attacks. ACTH plasma levels were 15 (10.5-20) pmol/l during and 15.7 (13.4-17) pmol/l outside attacks in common migraine. In classic migraine, plasma ACTH was 16 (7-36) pmol/l and 12.3 (8-28) pmol/l respectively. No significant differences were found between attacks and headache-free periods in common or classic migraine. Accordingly, we could not add evidence to the theory of a dysfunction of the endogenous opioid system in migraine.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Endorphins; Humans; Middle Aged; Migraine Disorders

Flunarizine (10 mg/day for 60 days) was given to eight postmenopausal women with common migraine. Plasma LH pulsatility fluctuation, peripheral concentrations of prolactin (PRL), cortisol, beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and Pain Total Index (PTI) were evaluated before and after treatment. PTI was significantly reduced by flunarizine, which did not affect beta-LPH, beta-EP and cortisol plasma levels. On the contrary, both PRL values and amplitude, and length of LH pulses had increased at the end of treatment. Flunarizine reduced head pain in postmenopausal women. However, the enhancement of both PRL and LH release indicates that this calcium antagonist might interfere with the dopaminergic tonus.

Topics: beta-Endorphin; Calcium Channel Blockers; Cinnarizine; Endorphins; Female; Flunarizine; Humans; Luteinizing Hormone; Menopause; Middle Aged; Migraine Disorders; Piperazines; Prolactin

Common migraine (CM) is an evolutive disease characterized by a progressive increase in the number of attacks and a consequent reduction in the free periods, eventually reaching a state of continuous migraine with interparoxysmal headache (MIH). To evaluate the role of central pro-opiocortin-related peptides in the pathogenesis of the disease, cerebrospinal fluid (CSF) levels of beta-lipotropin (beta-LPH), beta-endorphin (beta-EP) and ACTH were measured in two groups of migraine sufferers with increasing severity of the disease (CM and MIH), and in healthy controls. ACTH values were similar in the 3 groups, while beta-LPH levels were significantly lower (P less than 0.005) in patients affected by MIH (10.4 +/- 8.6 fmol/ml) than in patients with CM (35.7 +/- 8.3) and in controls (32.9 +/- 15.33). beta-EP levels were closely correlated with the severity of the disease: they decreased significantly from those found in healthy controls (86.1 +/- 37 fmol/ml) to those of CM sufferers (38.5 +/- 3.5; P less than 0.005) and showed a further significant fall (P less than 0.01) to the lowest levels which were found in MIH patients (14.8 +/- 9.8). These data showing that the progressive evolution of migraine is concomitant with a progressive impairment in the CSF levels of beta-EP, sustain the concept that non-organic central pain is related to a reduced activity of the neurons responsible for the CSF content of beta-EP.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Endorphins; Female; Humans; Male; Middle Aged; Migraine Disorders; Radioimmunoassay; Time Factors

Recently, the existence of a circulating peptide, beta-endorphin (B-EP) with potent analgesic properties has been revealed. Our group has evaluated B-EP plasma levels in several physiological and pathological models. The life span pattern of this newly identified hormone was characterized by a progressive increase during prepuberal development, by stable levels in adults with typical circadian and monthly variations, and by a decrease in aging subjects. Cerebrospinal fluid B-EP contents inversely showed a declining linear trend throughout life, which suggests an independent source of B-EP in this compartment. The concomitant changes in the reproductive system suggested the possible influence of gonads on B-EP plasma levels, as confirmed by decreasing B-EP levels in gonadectomized humans and rats. Headache, which is likely to occur concomitantly with hormonal milieu variations, appeared to be associated with a deficiency in the B-EP system, centrally and peripherally, the lowest values being found in the protracted forms of headache.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Aging; beta-Endorphin; Child; Child, Preschool; Endorphins; Female; Humans; Infant; Male; Menstruation; Middle Aged; Migraine Disorders; Pregnancy; Puberty

Basal and throughout-the-day variations of B-lipotropin (BLPH), B-endorphin (BEP), ACTH and cortisol plasma levels were studied in seven prepubertal children who had been affected by common migraine for periods of 6-26 months and in six healthy volunteers. Despite normal cortisol concentrations, children with migraine show higher BLPH (15.1 +/- 2.7 fmol/ml, M +/- SE), ACTH (25 +/- 2.7) and BEP (9.1 +/- 1.1) levels than controls. In both groups of children, evening values (8 p.m.) were significantly lower than morning values, but in migraineurs the decrease of the three peptides was less. The raised proopiocortin-related peptide plasma levels found in children suffering from migraine cannot be explained at present, although the discomfort experienced by the patients may create a situation of chronic stress which could explain such a finding. Whatever the explanation is, these findings differentiate prepubertal migraine from the most severe forms of headache occurring in adult life where lower than normal opioid levels have been demonstrated.

Topics: Adrenocorticotropic Hormone; Age Factors; beta-Endorphin; Child; Circadian Rhythm; Endorphins; Female; Humans; Hydrocortisone; Lipoproteins, LDL; Male; Migraine Disorders; Pituitary Hormones, Anterior; Pro-Opiomelanocortin; Protein Precursors

Topics: Adult; beta-Endorphin; Endorphins; Headache; Humans; Migraine Disorders; Radioimmunoassay

Beta-endorphin (RIA method, previous chromatographic extraction) was evaluated in plasma of migraine sufferers in free periods and during attacks. Decreased levels of the endogenous opioid peptide were found in plasma sampled during the attacks but not in free periods. Even chronic headache sufferers exhibited significantly lowered levels of beta-endorphin, when compared with control subjects with a negative personal and family history of head pains. The mechanism of the hypoendorphinaemia is unknown: lowered levels of the neuropeptide, which controls nociception, vegetative functions and hedonia, could be important in a syndrome such as migraine, characterized by pain, dysautonomia and anhedonia. The impairment of monoaminergic synapses ("empty neuron" condition) constantly present in sufferers from serious headaches, could be due to the fact that opioid neuropeptides, because of a receptoral or metabolic impairment, poorly modulate the respective monoaminergic neurons, resulting in imbalance of synaptic neurotransmission.

Topics: Adult; beta-Endorphin; Brain Chemistry; Chronic Disease; Endorphins; Female; Headache; Humans; Male; Middle Aged; Migraine Disorders; Radioimmunoassay

Eleven patients affected by common migraine (CM), eleven affected by daily chronic headache (DCH), and eight healthy volunteers were studied. Plasma levels of beta-endorphin (beta EP), beta-lipotropin (beta LPH). ACTH and cortisol were measured in basal conditions and after traditional Chinese acupuncture (TCA). Basal beta LPH and beta EP plasma levels (pg/ml) in the DCH patients (57.6 +/- 9.5 and 16.8 +/- 2.5, respectively; M +/- SE) were lower than those found in the controls (83.6 +/- 13.7 and 26.0 +/- 6.1; p less than 0.001), while those found in the CM cases showed inter-mediate values (75.3 +/- 12.0 and 24.4 +/- 5.8). ACTH and cortisol concentrations in both the CM and DCH patients were in the same range as those of the control group. TCA caused an increase in beta LPH and beta EP plasma concentrations in the control group (beta LPH: 117 +/- 16.9; beta EP: 44.1 +/- 6.7). Opioid plasma levels, however, remained unmodified after TCA in both the CM and DCH groups. ACTH plasma levels remained stable after TCA in all three subject groups. Patients suffering from primary headache are characterized by low beta LPH and beta EP plasma levels and by a poor reactivity of circulating opioids to non-stressful stimuli.

Topics: Acupuncture Therapy; Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Chronic Disease; Endorphins; Female; Headache; Humans; Hydrocortisone; Male; Middle Aged; Migraine Disorders