naloxone and Migraine-Disorders

Topics: Anesthetics, Local; Anti-Bacterial Agents; Charcoal; Drug Synergism; Drug Therapy, Combination; Epinephrine; Humans; Hypertension; Migraine Disorders; Naloxone; Parkinson Disease

Topics: Analgesia; Analgesics, Opioid; Animals; Brain; Endorphins; Enkephalins; Humans; Migraine Disorders; Naloxone; Neural Pathways; Norepinephrine; Pain; Receptors, Opioid; Sensory Thresholds; Serotonin; Spinal Cord

Having a differential sensitivity to morphine can distinguish migraine suffers from healthy people who are headache-exempt. The aim of the present study was to investigate whether such an abnormal response to morphine challenge is entirely dependent on opioid receptor activation. A role for excitatory amino acids and gamma-aminobutyric acid has been proposed on the basis of the effect of diazepam. As opposed to naloxone, this gamma-aminobutyric acid agonist was found to inhibit the adverse effects of low doses of morphine in migraine sufferers, while at the same time being able to almost abolish morphine-induced miosis in subjects who underwent a short-lasting chronic pretreatment. The capacity of diazepam either to control the adverse effects of morphine or to induce well-being in subjects known to suffer from a central neurogenic pain such as migraine, is noteworthy even regarding the clinical treatment of other painful conditions, such as deafferentation pain, which is known to be not satisfactorily treated by using morphine.

Topics: Adult; Cross-Over Studies; Diazepam; Double-Blind Method; Excitatory Amino Acids; gamma-Aminobutyric Acid; Humans; Migraine Disorders; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Pain; Receptors, Opioid

Topics: Adult; Body Image; Female; Humans; Male; Migraine Disorders; Naloxone; Pentazocine; Perceptual Disorders; Pupil; Visual Perception

Topics: Adult; Body Image; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Migraine Disorders; Naloxone; Pentazocine; Perceptual Disorders; Random Allocation; Scotoma; Time Factors

This study was planned as a pilot study to determine to what extent acupuncture might help in severe cases of migraine and, if possible, to see whether the mechanism was endorphin mediated. The study was carried out on 16 subjects who had severe and regular migraine for more than five years (mean duration 24 years). The study lasted eight months and was divided into four blocks of two months each: pre-treatment, treatment block I, treatment block II, and post-treatment. It was double-blind and cross-over in design. Acupuncture was found to cause a significant change in the number of headaches and their duration, with 40% of the subjects showing a 50%-100% reduction. Although pain sensation was not altered, attacks were less severe and less often accompanied by nausea and vomiting. At no stage was there any difference between subjects receiving saline or naloxone so that the possibility of a non-endorphin mechanism must be considered.

Topics: Acupuncture Therapy; Adult; Consumer Behavior; Double-Blind Method; Endorphins; Female; Humans; Male; Middle Aged; Migraine Disorders; Naloxone; Pilot Projects

Vagus nerve stimulation (VNS) is a promising neuromodulation approach used in the treatment of migraine, whose therapeutic mechanism is largely unknown. Previous studies suggest that VNS's anti-nociceptive effects may, in part, involve engaging opioidergic mechanisms. We used a validated preclinical model of head pain, with good translational outcomes in migraine, acute intracranial-dural stimulation, which has responded to invasive VNS. We tested the effects of μ (MOR), δ (DOR) and κ (KOR) opioid receptor agonists in this model, and subsequently the effects of opioid receptor antagonists against VNS-mediated neuronal inhibition. MOR, DOR, and KOR agonists all inhibited dural-evoked trigeminocervical neuronal responses. Both DOR and KOR agonists also inhibited ongoing spontaneous firing of dural responsive neurons. Both DOR and KOR agonists were more efficacious than the MOR agonist in this model. We confirm the inhibitory effect of invasive VNS and demonstrate that this effect was prevented by a broad-spectrum opioid receptor antagonist, and by a highly selective DOR antagonist. Our data confirm the role of MOR in dural-trigeminovascular neurotransmission and additionally provide evidence of a role of both DOR and KOR in dural-nociceptive transmission of trigeminocervical neurons. Further, the results here provide evidence of engagement of opioidergic mechanisms in the therapeutic action of VNS in headache, specifically the DOR. These studies provide further support for the important role of the DOR in headache mechanisms, and as a potential therapeutic target. The data begin to dissect the mode of action of the analgesic effects of VNS in the treatment of primary headache disorders.

Topics: Action Potentials; Analgesics, Opioid; Animals; Fentanyl; Migraine Disorders; Naloxone; Narcotic Antagonists; Neurons; Rats; Receptors, Opioid; Vagus Nerve Stimulation

The degree and duration of miosis, induced by low doses of parenteral morphine (65 mcg/Kg i.m.) before and after ten days of naloxone treatment, were evaluated in eleven volunteers affected by migraine without aura. Morphine induced miosis was significantly more intense and persistent after chronic naloxone treatment than before the drug was administered. In another group of seven volunteers suffering from migraine without aura, no differences between morphine-induced miosis, prior to and after a ten-day treatment with placebo, were observed. In addition, a third group of fifty-four subjects, suffering from migraine without aura, underwent three-month naloxone treatment (150 mcg/Kg/i.m./day). All subjects included in the third group, were partially or totally refractory to conventional therapy. Pupillopharmacological results indicate that the benefit gained from chronic administration of the opiate antagonist may be related to some type of naloxone-induced supersensitivity of the opioid receptor population.

Topics: Adult; Female; Humans; Male; Migraine Disorders; Miosis; Morphine; Naloxone; Pupil

The effects of naloxone and a met-enkephalin analogue on head pain, vascular responses, and autonomic-associated symptoms were studied in 24 migraine patients, 12 patients suffering from tension-type headache, and 24 normal subjects in whom headache was induced by intravenous injections of increasing doses of histamine (histamine test). A hypersensitivity to histamine was found in migraine patients. Naloxone slightly increased the intensity of pain in migraine and tension-type headache sufferers. The met-enkephalin analogue did not affect the intensity of pain in migraine patients, tension-type headache patients, and normal subjects, but it reduced the intensity and duration of facial flushing (p less than 0.001) and the autonomic symptoms (p less than 0.001) in migraine patients when the pretreatment was not given shortly before histamine. In migraine patients, there seems to be an increased reactivity (receptor supersensitivity?) to the met-enkephalin analogue at the level of systems that inhibit facial vasodilatation and autonomic symptoms.

Topics: Adult; Autonomic Nervous System; Enkephalin, Methionine; Female; Flushing; Headache; Histamine; Humans; Male; Migraine Disorders; Naloxone; Pain Measurement

To assess the biological correlates of the precipitation of migraine attacks in the perimenstrual period, plasma beta-endorphin (beta-EP) and cortisol responses to naloxone (8 mg iv) and corticotropin releasing hormone (100 micrograms iv) were evaluated in both the follicular phase and the premenstrual period in 7 patients suffering from menstrual migraine and in 7 healthy, asymptomatic control volunteers. In the controls, naloxone evoked a significant release of both beta-EP (F = 5.86, p less than 0.002) and cortisol (F = 4.43, p less than 0.008), independently of the menstrual cycle phase (F = 0.31 and 1.04, for beta-EP and cortisol, respectively). Menstrual migraine patients, on the other hand, showed a significant hormone response only in the follicular phase, not in the premenstrual period. Corticotropin releasing hormone significantly increased beta-EP and cortisol in both the controls and the menstrual migraine patients, independently of the menstrual cycle phase. In both the naloxone and corticotropin releasing hormone testings, the basal beta-EP levels measured in the premenstrual period were lower than those observed in the follicular phase (p less than 0.02). These data demonstrate a cyclical, premenstrual dysfunction of the hypothalamic control exerted by opioids on the hypothalamus-pituitary-adrenal axis. Impairment of this fundamental adaptive mechanism (involved in stress responses and in pain control) could establish a causal relationship between menstrual-related migraine attacks and premenstrual opioid hyposensitivity.

Topics: Adult; Endorphins; Female; Humans; Hypothalamo-Hypophyseal System; Menstrual Cycle; Migraine Disorders; Naloxone; Pituitary-Adrenal System

The evaluation of central opiate activity could be of clinical value in the diagnosis and treatment of pain syndromes. The current approach via direct measurement of endogenous opioid peptides in cerebrospinal fluid (CSF) is not devoid of side effects and cannot be used in every-day practice. As an alternative to this method, we have studied the neuroendocrine response of plasma LH to an i.v. naloxone injection in 39 headache sufferers from different diagnostic subgroups, and in 12 age- and sex-matched healthy volunteers. Patients (19 females and 20 males) were affected by common migraine (CM, 11 cases), migraine with interparoxysmal headache (MIH, 9), classical migraine (CIM, 9), and chronic cluster headache (CH, 10). Headache lasted 3-36 years. Prior to naloxone challenge (4 mg i.v.), LH pulsatility was evaluated for 1 h. The next morning, the pituitary response to LH-RH (10 micrograms i.v.) was tested in 20 patients. Plasma LH was measured by RIA in every sample. The response to the tests was evaluated as secretion area of plasma LH minus the mean basal value. Controls (497.5 +/- 85.5 mIU/ml x 120 min), ClM (357.8 +/- 78.9) and CH (450.5 +/- 70.4) patients showed similar results, while in cases of CM (155.3 +/- 71.7, P less than 0.05) and MIH (104.1 +/- 53.7, P less than 0.01) the LH secretion after naloxone injection was significantly blunted. On the contrary, the response of LH to LH-RH was similar in controls and patient groups, thus excluding pituitary dysfunctions in this response.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Cluster Headache; Endorphins; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Migraine Disorders; Naloxone; Vascular Headaches

In order to evaluate the relationships between endogenous opioid activity and premenstrual complaints, we subjected three groups of patients in the mid (days 8-12 prior to menses) and late (days 1-5 prior to menses) luteal phases of the cycle to a naloxone test and some of the patients to a luteinizing-hormone-releasing hormone (LHRH) test. The premenstrual syndrome (PMS) group was composed of nine patients complaining of dizziness, irritability and depression close to menses for at least three years. The menstrually related migraine (MM) group was composed of 15 patients complaining of premenstrually related migraine. The common migraine (CM) group was made up of 16 women suffering from common migraine for years whose attacks occurred independently of menstrual cycle events. A group of seven fertile women served as controls. Every two days the patients filled out the Menstrual Distress Questionnaire for evaluation of their complaints. After the evaluation of spontaneous LH pulsatility for one hour, 4 mg of naloxone was injected as a bolus, and samples were collected every 15 minutes for 2 hours. Both estradiol (E2) and progesterone (P) were measured in basal samples from each naloxone test. LH responsiveness to LHRH was similar in the mid and late luteal phases and did not change between groups. In the mid luteal phase the LH response to naloxone in PMS and MM patients was similar to that in normal subjects, while CM patients had impaired LH secretion. In the premenstrual phase only the controls maintained an LH responsiveness similar to that observed in the mid luteal phase, while both PMS and MM lost the naloxone-induced LH release.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Endorphins; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Luteinizing Hormone; Middle Aged; Migraine Disorders; Naloxone; Premenstrual Syndrome; Progesterone

Topics: Adult; Cluster Headache; Female; Humans; Luteinizing Hormone; Male; Middle Aged; Migraine Disorders; Naloxone; Vascular Headaches

The effects exerted by ovarian steroids on the modulation of opioid activity were investigated in post-menopausal migraine sufferers and in healthy controls. In order to evaluate central opioid tonus, plasma LH rise after naloxone injection was measured, bearing in mind the tonic inhibition of endogenous opioid on hypothalamic LH-RH. There was no response of plasma LH to naloxone in post-menopausal women or in patients submitted to ovariectomy in fertile life. When the subjects underwent a sequential estrogens + progestagens therapy, such a response was noted from the first month of treatment; progestagens alone were ineffective. The same phenomena were also evident in post-menopausal migraine sufferers. These data indicate that ovarian steroids modulate the activity of opiate receptors in both healthy women and migraine sufferers. Interestingly, replacement therapies through ovarian steroids restored the activity of central opioid tonus in patients affected by migraine.

Topics: Adult; Aged; Estradiol Congeners; Estrogens, Conjugated (USP); Female; Humans; Luteinizing Hormone; Menopause; Menopause, Premature; Middle Aged; Migraine Disorders; Naloxone; Progesterone Congeners; Receptors, Opioid

Topics: Animals; Cerebrovascular Disorders; Humans; Migraine Disorders; Naloxone; Spinal Cord Injuries

PRL response to morphine in a group of migraine subjects was studied in the baseline condition and after neuroendocrinological inhibition and stimulation tests. No significant differences were found in comparison with control subjects. This demonstrated the integrity of the opioid system and serotoninergic pathways in migraine subjects.

Topics: Adult; Brain; Drug Interactions; Female; Humans; Metergoline; Migraine Disorders; Morphine; Naloxone; Pizotyline; Prolactin; Receptors, Opioid; Serotonin

A basilar migraine with alexia without agraphia and episodes of dysmnesia was treated with naloxone. The triggering of an attack by angiography, allowed to see an arterial spasm. The beneficial effect of naloxone is discussed, together with the respective roles of spasm and neuronal metabolic changes in the mechanisms of symptoms and signs.

Topics: Adult; Agraphia; Basilar Artery; Dyslexia, Acquired; Hemianopsia; Humans; Male; Migraine Disorders; Naloxone; Neurons; Radiography; Spasm; Vertebral Artery

The aim of this study is to make an evaluation of the activity of endogenous opioid tonus in patients affected by menstrual migraine. We tested the LH response to naloxone injection, an opiate receptor antagonist, in 18 migraineurs in the early and late luteal periods going towards the attacks. The lack of any response in the latter group demonstrates an opioid disregulation in this kind of pathology.

Topics: Adult; Female; Humans; Luteinizing Hormone; Menstruation; Migraine Disorders; Naloxone; Receptors, Opioid

Tachyphylaxis (TPX) to the spasmogenic activity of 5HT can be demonstrated in vivo in the superficial hand dorsal veins in man by the computerized venotest. The 5HT-TPX is reverted by previous local naloxone administration. Tachyphylaxis to 5HT is usually absent in the migraineur. The restored 5HT spasmogenic effect by naloxone suggests the possibility of local opioid apparatus participation in TPX to 5HT.

Topics: Adolescent; Adult; Female; Hand; Humans; Male; Middle Aged; Migraine Disorders; Naloxone; Receptors, Opioid; Serotonin; Serotonin Antagonists; Tachyphylaxis; Vasoconstriction; Veins

The Authors, starting with the hypothesis that could exist a correlation between the opiate withdrawal and the migraine crisis, used the naloxone, opiate pure antagonist, in order to induced the migraine crisis. 30 patients affected by migraine were studied; naloxone was administered acutely (2 mg e.v.) during the asintomatic period. The naloxone administration never caused the migraine crisis. The patients didn't complain variations regarding the psycho-physical status or the monitored clinical parameters.

Topics: Adolescent; Adult; Female; Humans; Male; Middle Aged; Migraine Disorders; Naloxone; Narcotics; Substance Withdrawal Syndrome

Two cases of non-familial hemiplegic migraine are described. Naloxone reversed the neurological deficits accompanying attacks, whereas the pain was uninfluenced. The possibility that the opiate-antagonist naloxone facilitates regression of neurological symptoms associated with migraine attacks in general is voiced.

Topics: Adult; Female; Hemiplegia; Humans; Male; Migraine Disorders; Naloxone

The responses to work-test in ischemia (tourniquet technique), before and after I.V. injection of naloxone (2 mg) or saline, were investigated in healthy volunteers and patients suffering from various types of headache. The patients were examined during both painful and painless periods. We found that only the subjects suffering from migraine showed a significantly shortened pain tolerance at work-test in ischemia, after injection of naloxone, and only during painful periods. Psychogenic headache patients and migraine patients in painless periods showed responses during work-test similar to those in healthy volunteers, even after injection of naloxone. We believe that hyperalgesic effect of naloxone is due to involvement of beta-endorphin systems only during organic pain.

Topics: Adult; Arm; Double-Blind Method; Female; Headache; Humans; Ischemia; Male; Migraine Disorders; Naloxone; Pain; Sensory Thresholds; Sodium Chloride