Biomedical subjects

F Sicuteri

Publications and source records attributed to F Sicuteri.

At least 37 records · Page 2Linked to original sources

PubMed1994

Oral sumatriptan compared with placebo in the acute treatment of migraine.

This multicentre, double-blind, parallel-group study compared the efficacy, safety and tolerability of oral sumatriptan, given as a new film-coated tablet, with placebo in the acute treatment of migraine. Patients were randomised unequally (1:2) to receive placebo or sumatriptan. Eighty-eight patients received placebo (plus an optional dose 2 h later if the headache persisted plus a further optional dose for recurrence within 24 h) and 162 patients received sumatriptan 100 mg (plus an optional 100 mg dose at 2 h and an optional 100 mg dose within 24 h). Sumatriptan was significantly more effective than placebo at relieving headache (defined as reduction in severity from severe or moderate pain to mild or no pain) at 2 h (51% versus 31%, P = 0.003) and 4 h (71% versus 35%, P < 0.001). Fewer sumatriptan-treated patients required a second dose compared with placebo-treated patients (49% versus 74%, P < 0.001). More sumatriptan-treated patients were completely pain free compared with placebo-treated patients at both 2 h (24% versus 12%) and 4 h (48% versus 18). Patients receiving sumatriptan reported earlier onset of headache relief than patients receiving placebo. Headache relief in sumatriptan-treated patients was similar, irrespective of the type of migraine (with or without aura) or the time of treatment < or = 4 h or > 4 h after onset of migraine). Sumatriptan was more effective than placebo at relieving nausea, vomiting and photophobia/phonophobia. Few patients were evaluable for treatment of headache recurrence, and statistical analysis was not possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1994

Lowered circannual urinary melatonin concentrations in episodic cluster headache.

The circannual secretion of melatonin in 14 Swedish and 15 Italian patients suffering from episodic cluster headache was compared with 14 Swedish and 15 Italian healthy controls matched for sex and age. Overnight samples of urine were collected once a month from 8 to 14 months and kept at -20 degrees C until analysed with RIA. The melatonin concentrations in nocturnal urine were permanently low in cluster headache and there was no consistent change of the melatonin concentration in relation to cluster periods occurring during the study. There was no definitive circannual or infraannual rhythmicity of melatonin in patients or controls. Multiple analysis of variance with repeated measurements showed a significant effect of disease (p < 0.05), but not of time. Sex, geographical location, age, and smoking also had significant effects (p < 0.001) on the melatonin concentrations. Lower melatonin levels in cluster headache patients than in controls may in part be related to a larger number of smokers in the patient group. The relation between tobacco use and melatonin should be further studied.

Adult↗

PubMed1994

Visceral pain threshold is deeply lowered far from the head in migraine.

A short-lasting over-distension of the hand-forearm veins, obtained through a non-invasive original maneuver (Hand Arm Vein Distension test) induces local pain when applied to migraine sufferers in inter-critical period. Conversely, subjects with an absolutely negative personal and family history for any type of idiopathic headache do not report any pain or only an uncertain, slight one. The injection of 1 mL of 2% to 8% (i.e. 0.34 mol/L to 1.36 mol/L) hypertonic saline into the antecubital vein during an extemporary short (1 minute) circulatory blockage (ischemia induced to guarantee a strictly local action of the chemical stimulus) provokes moderate, strong or unbearable local (arm vein) pain in migraine sufferers but not in subjects with a personal and family history absolutely free from any type of headache. These results show for the first time that migraineurs show a proneness to visceral pain in viscera (veins) distant from the head (arm-hand). Such a finding is consistent with the theory that migraine pain is due to a central derangement of the viscerosensory system.

Adult↗

PubMed1993

Possible long-lasting inhibition of converting enzyme by enalapril in human cerebrospinal fluid.

1. Converting enzyme and neutral endopeptidase activities were both measured every 3 h by a fluorimetric method in plasma and cerebrospinal fluid of patients diagnosed as migraineurs with aura after lumbar puncture, which was performed 9 h after an acute oral dose of enalapril or placebo. 2. A reduced converting enzyme activity, as compared with placebo, was observed in patients who were given enalapril. On the other hand, neutral endopeptidase activity detected after enalapril did not differ from that measured after placebo. 3. The results seem to indicate that enalapril penetrates the blood-brain barrier in sufficient amounts to reduce converting enzyme activity. Moreover, neutral endopeptidase was not affected by enalapril. Therefore, those clinical effects of the drug which have been attributed to the involvement of central opioid mechanisms may depend on the inhibition of brain converting enzyme but not the inhibition of brain neutral endopeptidase.

Adult↗

PubMed1993

Hypothalamic modulation of nociception and reproduction in cluster headache. I. Therapeutic trials of leuprolide.

A slow-release gonadotropin-releasing hormone (Gn-RH) analogue was administered to 30 males suffering from chronic cluster headache (CH) in a placebo-controlled study with the aim of enhancing neurotransmission in the pain-suppressing systems of the hypothalamus through a feedback action involving neuroendocrine functions too. A significant improvement in the severity of the pain occurred together with the expected lowering of the libido and serum levels of testosterone and luteinizing hormone. We postulate that the benefit of the Gn-RH analogue relates to an impairment of neuronal modulation in cluster headache.

Adult↗

PubMed1993

Hypothalamic modulation of nociception and reproduction in cluster headache. II. Testosterone-induced increase of sexual activity in males with cluster headache.

Short-lasting chronic testosterone administration did not change the course of cluster headache in seven chronic sufferers, whereas it enhanced sexual excitement in comparison with male control subjects who received the same treatment. We postulate that the sexual excitement induced in cluster headache sufferers by chronic treatment with testosterone relates to an impairment of neuronal modulation in this disorder.

Adult↗

PubMed1993

Phantom tooth diagnosis and an anamnestic focus on headache.

The cause of atypical odontalgia has been related to many factors, including psychological ones. Animal experiments indicate that tooth pulp extirpation provokes a deafferentation, which may or may not induce pain, depending on unknown factors. The research described here showed that human tooth avulsion induces atypical odontalgia when it is carried out in migraine and cluster headache sufferers. Conversely, no sensation is reported by personally and familiarly headache-exempt subjects who underwent the same type of tooth extraction.

Case-Control Studies↗

PubMed1992

Chronic naloxone administration, a potential treatment for migraine, enhances morphine-induced miosis.

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.

Adult↗

PubMed1991

Idiopathic headache as a possible risk factor for phantom tooth pain.

Following tooth pulp extirpation, some subjects suffer from persistent pain which affects edentate sites in absence of any local pathology. As regards this peculiar pain, called phantom tooth pain (PTP), what is puzzling is the fact there is a low prevalence of PTP in a very large population showing identical conditions of tooth pulp extirpation. The present investigation indicates that PTP mainly affects migraine (M) and cluster headache (CH) sufferers, whereas it does not affect subjects who have a negative personal and family history for idiopathic headache (IH). These results circumscribe the presence of PTP to a specific section of the population. The present results, besides indicating that PTP may be the result of a peculiar neuronal predisposition relating to IH pathogenesis, suggests some practical therapeutic hints. In fact, successful anti- M and anti-CH prophylactic treatment greatly improve PTP syndrome.

Cluster Headache↗

PubMed1991

Visceral and somatic profiles of needless pain and nonpainful sensations in idiopathic headache.

The syndromes commonly called idiopathic headaches (IH) are the most frequent painful pathologies. The term derives from the fact that the IH necessarily but not exclusively involve the head area. Having abandoned the etiopathogenetic criterion of classification (vascular and tension headaches) which was proposed many years ago, The International IH Society has introduced a phenomenonological/descriptive classification, which is logically sound considering the idiopathy and clinical multiformity of IH. This classification may be useful until it is possible to substitute it with a nosography based on sure etiological data. The distinction between "chronicized" migraine (migraine attacks with daily intercritical headache) and tension-type headaches perhaps represents the greatest diagnostic difficulty, since the two forms require different therapeutic tools even though they have clinical analogies. In our center we are developing a nosological method to differentiate tension-type headaches from chronicized migraines on the basis of a criterion that is theoretically sound because it draws on the anatomofunctional features of these IH, and practical because it is easy to apply. This method is founded on solid algological knowledge. In fact, the IH are simply the most common manifestations of the spontaneous activation of the sensory/pain transmitting afferences, decodified at the level of the integrative areas as "useless" painful and nonpainful sensations of either a visceral or a somatic type, according to the type of IH. The adjective "idiopathic," attributed to the IH, refers to the uselessness of the sensations which dominate these syndromes. They are useless because they are not induced by harmful, environmental, or endogenous stimuli, and do not culminate in a passive or active defensive reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Headache↗

PubMed1991

Links between headache mechanisms and new medications.

A milestone in migraine (M) treatment was the discovery of the dramatic analgesic action of a nonanalgesic drug, ergotamine. The second step consisted in the identification of the prophylactic power of serotonin antagonists, particularly methysergide, in support of the serotonin theory of M. A growing number of drugs has widened the therapeutic resources in this area and at the same time has raised more and more complex and fascinating pathogenetic questions. According to the personal theory, pain in idiopathic headaches (IH) is the clinical expression of an automatism of transmission of painful signals along the neuroaxial sensory pathways. This automatism is in turn linked to a fault in the suprespinal pain modulating systems. This is a similar, but obviously not identical, situation to that of automatic pain transmission in organic deafferentation. As animal experiments have shown, the activation of the afferents may cause the retrograde (antidromic) release of substance P (SP) (and of the neurokinins related to it). This substance is devoid of algogenic capacity but endowed with a high capillary permeabilizing power, with consequent neurogenic edema (NGE) due to plasma overflow. The heavy and lasting edema provoked in both the forearm and the hand by injection of both SP and releasing histamine 48/80 b.w. into the humeral artery, is by no means painful, unlike that induced by injection into the superficial temporal artery (moderate urent pain), probably because of the greater sensitivity of the vascular structures of the head. It may be postulated that the repeated episodes of NGE may lead to a "sterile" phlogosis (neurogenic inflammation) which is capable of increasing and prolonging the pain in the periphery.(ABSTRACT TRUNCATED AT 250 WORDS)

Cluster Headache↗

PubMed1990

Characterization of endopeptidase 3.4.24.11 ("enkephalinase") activity in human plasma and cerebrospinal fluid.

The presence of the neutral metallo-endopeptidase 3.4.24.11 ("enkephalinase") activity was investigated by fluorimetric assay in human body fluids. Although the enzyme was previously known to occur exclusively in membrane bound form in the human or animal central nervous system, its activity was detected in human cerebrospinal fluid (CSF), plasma and amniotic fluid. Although the endopeptidase 3.4.24.11 activity found in human body fluids has properties closely related to the membrane bound enzyme such as affinity constant for the inhibitors, optimal pH and Km for the substrate, the Vmax values were in CSF, plasma and amniotic fluid, respectively, 2 x 10(3), 10(2), 10 lower than mouse brain homogenate.

Adult↗

PubMed1990

Release of sensory neuropeptides from dural venous sinuses of guinea pig.

Substance P- and calcitonin gene-related peptide-like immunoreactivities (SP-LI and CGRP-LI, respectively) were measured in superfusates of either superior sagittal sinus and transverse sinuses and attached dura mater or dura mater alone of guinea pig. Exposure of cerebral venous sinuses to capsaicin (1 microM) evoked the release of both SP-LI and CGRP-LI, which was no longer observed upon second challenge with the drug. Neuropeptide release was induced by 80 mM K+ either at the first or second administration. Bradykinin (10 microM) increased the outflow of CGRP-LI, but not of SP-LI, from cerebral venous sinuses. In vitro capsaicin pretreatment (10 microM) or incubation with 10 microM indomethacin completely abolished the bradykinin-evoked CGRP-LI release. Capsaicin (1 microM) failed to evoke release from dura mater without major intracranial venous vessels. Sensory neuropeptide released from the cerebral venous sinuses may take part in certain symptoms, such as vasodilatation and inflammation accompanying the pain of the migraine attack. Bradykinin, putatively via prostanoid generation, may participate in this event.

Animals↗

PubMed1990

Substance P theory: a unique focus on the painful and painless phenomena of cluster headache.

These studies of cluster headache (CH) focus on two key features of pain transmission: a) sensory nerves when stimulated, as well as the expected afferent transmission, also display an efferent function which affects capillaries, glands, and smooth muscle (of the iris in CH); substance P (SP) and allied transmitters such as Vasoactive Intestinal Peptide (VIP) and Calcitonin Gene-Related Peptide (CGRP) are the main agonists of this dual afferent-efferent function; b) impaired pain transmission (deafferentation-like condition) provokes a rostral spread of neuronal irritability and automatic firing ("quasi epileptic foci") producing a clinical predilection for pain with the generation of "spontaneous" pains along the sensory pathways. The substrates studied in the present experiments are the iris, salivary glands, and nasal mucosa. 1) Iris: the conjunctival instillation of SP induces isocoric miosis both in CH sufferers and in normals, thus excluding gross SP receptoral dysfunction of the iris muscle in CH. Electrical stimulation of extraocular (infratrochlear) endings of the first branch of the trigeminal nerve provokes a miosis, which is significantly less in the symptomatic eye than in the contralateral one. This miosis is ascribed to a retrograde release of SP, induced by electrical stimulation of the trigeminal ophthalmic branch. The relatively poor miosis in the painful eye could correlate with a deficient release of SP from the sensory terminals in the iris. 2) Salivary glands: an increase of substance P-like immunoreactivity is found in the saliva taken from the asymptomatic side, but not from the painful side during a cluster headache attack, thus showing at this level also an asymmetry as previously shown in other head structures. 3) Nasal mucosa: intranasal application of capsaicin, a powerful releaser of SP from sensory terminals, evokes an immediate burning pain in the ipsilateral nasal, ocular, and temporal areas, as well as lacrimation and rhinorrhea. A gradual decrease (tachyphylaxis) of these phenomena is consistently observed after few days of daily nasal administration of capsaicin. When this treatment is applied to CH patients, a rapid decrease in the number and intensity of attacks, and even disappearance of symptoms accompanies the decline of the capsaicin-induced manifestations. Local (nasal) capsaicin, in spite of evoking immediately the same vegetative (rhinorrhea, lacrimation, conjunctival congestion) and in part nociceptive (transient nasal, ocular, temporal burning) phenomena of CH, never has been able to provoke delayed spontaneous-CH like attacks. Such delayed provoked attacks, one of the most pregnant phenomena in CH investigations, are almost constantly evoked by systemic stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Capsaicin↗

PubMed1989

Thiorphan increases capsaicin-evoked release of substance P from slices of dorsal spinal cord of guinea pig.

Capsaicin-evoked release of substance P-like immunoreactivity (SP-LI) from dorsal horn slices of guinea pig spinal cord was unaffected by incubation with the converting enzyme inhibitor captopril (10 microM). However, incubation with the endopeptidase 24.11 inhibitor, thiorphan (10 microM), induced a 2.44-fold increase of capsaicin-evoked SP-LI release, leaving the capsaicin-evoked release of calcitonin gene-related peptide (CGRP)-LI unchanged. Endopeptidase-24.11 activity was higher in homogenates of the dorsal than ventral spinal cord. Endopeptidase-24.11 might be involved in the inactivation of SP released from central endings of primary sensory neurons.

Animals↗

PubMed1989

Unilateral impairment of pupillary response to trigeminal nerve stimulation in cluster headache.

The pupillary constriction induced ipsilaterally by transcutaneous electrical nerve stimulation (TENS) of the infratrochlear nerve was measured, using an electronic pupillometer, in 26 episodic cluster headache (CH) and 15 migraine sufferers tested during an attack-free period and in 16 healthy controls. In controls, TENS gave rise to a miosis which was slow in onset and long-lasting in duration, and which was comparable to that mediated by tachykinins in animals. A similar miotic response was bilaterally observed in migraine patients and in CH patients examined during the inactive phase. In CH sufferers during the cluster period, TENS only elicited a normal pupillary constriction in the asymptomatic eye, whereas the resulting response in the symptomatic eye was markedly decreased. Although the exact mechanism underlying the dysfunction remains to be clarified, these results seem to indicate that ocular trigeminal pathways are involved in CH.

Adolescent↗

PubMed1989

Cluster headache in the male: sex steroid pattern and gonadotropic response to luteinizing hormone releasing hormone.

Serum testosterone, dihydrotestosterone, delta 4-androstendione and 17 beta-estradiol, sex hormone binding globulin (SHBG) and gonadotropic response to luteinizing hormone releasing hormone (LHRH) were studied in 34 male subjects with episodic or chronic cluster headache (CH). The sex steroid free fractions and those bound to SHBG and albumin were determined by a simulatory computerized method based on the mass action law. Individual steroid values were dispersed over a wide range in CH patients. Total, free and carrier protein-bound testosterone levels were significantly diminished only in chronic CH, where luteinizing hormone (LH) peak values after intravenous administration of LHRH were also decreased. Basal and peak follicle stimulating hormone (FSH) levels were significantly increased in episodic and in chronic CH groups, in comparison to healthy controls.

Adult↗

PubMed1989

Reduced serotonin vascular sensitivity in ergotamine abusers.

The action of ergotamine on the 5-hydroxytryptamine (5-HT) venous sensitivity was studied in ergotamine abuser and non-abuser migraine patients. Ergotamine abusers showed reduced 5-HT hand vein contraction during abuse, compared to seven days after ergotamine withdrawal. In non-ergotamine users, the 5-HT venoconstriction was not significantly modified 12 h after a single intramuscular ergotamine (0.25 mg) administration. Even the administration of ergotamine locally into the vein did not change the venospasm of 5-HT given acutely in the same vein. Therefore, it seems that the 5-HT antagonism does not contribute to the therapeutic effect of ergotamine during the migraine attack. Moreover, the reduced 5-HT responsiveness during ergotamine abuse may possibly be compatible with the chronic headache present in some abusers, the withdrawal headache attacks and the abuse itself.

Adult↗