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Biomedical subjects

M Nicolodi

Publications and source records attributed to M Nicolodi.

At least 19 recordsLinked to original sources
PubMed1998

Fibromyalgia and headache. Failure of serotonergic analgesia and N-methyl-D-aspartate-mediated neuronal plasticity: their common clues.

A defect in serotonergic analgesia and a hyperalgesic state are proposed as features common to headache and fibromyalgia. The benefit to both migraine and fibromyalgia from inhibiting ionotropic N-methyl-D-aspartate receptor activity implies that redundant hyperalgesia-related neuroplastic changes are crucial for severe or chronic migraine and primary fibromyalgia. The fact that migraine and primary fibromyalgia share some pivotal set-up of serotonergic and excitatory amino acid systems led us to analyse epidemiological data supporting the hypothesis that analgesic disruption and a consequent hyperalgesic state are mechanisms of both migraine and fibromyalgia. Beyond demonstrating the comorbidity between migraine and primary fibromyalgia, the data suggest that migraine may represent a risk factor for fibromyalgia.

Analgesics↗
PubMed1998

Painful and non-painful effects of low doses of morphine in migraine sufferers partly depend on excitatory amino acids and gamma-aminobutyric acid.

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.

Adult↗
PubMed1998

Negative modultors of excitatory amino acids in episodic and chronic migraine: preventing and reverting chronic migraine. Special lecture 7th INWIN Congress.

The mechanism capable of transforming episodic migraine into chronic migraine is attributed by the authors to hyperalgesia and related neuroplastic changes, chiefly long-term potentiation, due to the action of excitatory amino acids, chiefly the ones acting at N-methyl D-aspartate (NMDA) receptor. A preeminent role has been attributed to 'third hyperalgesia', a newly observed type of hyperalgesia which is inheritable and can act as a ground for the above-mentioned mechanism of 'chronicization' of migraine. The role of primary and secondary hyperalgesia in giving redundance to neuraxial abnormalities is also discussed. The fact that NMDA noncompetitive antagonist ketamine and gabapentin, inhibitor of the neuronal synthesis of L-glutamate, can cure chronic migraine, so far considered refractory to prophylactic therapies, gives indirect but evident support to the mechanism suggested above. The antinociceptive role of the above-mentioned negative modulators of excitatory amino acids and the possible interplay between ionotropic and metabotropic receptors are also taken into consideration.

Acetates↗
PubMed1997

Phantom eye: features and prevalence. The predisposing role of headache.

We prospectively evaluated the frequency, time-course and predisposing factors of phantom eye syndrome in 53 patients who underwent surgical eye amputation to cure ocular cancer. Before surgery, patients were classified as Group I (n = 25) if they had no history of headache or Group II (n = 28) if they were headache sufferers. Three clinical patterns were distinguished: phantom pain, non-painful phantom phenomena and photopsias. Their symptoms developed 7 days to 6 months after surgery, with peak incidence after 6 months (photopsia 43%; phantom pain 28%; non-painful phantom phenomena 62%). Phantom eye syndrome was more common in headache sufferers than in non-headache subjects. Headache sufferers were more prone to phantom pain, but more so to non-painful phenomena and photopsias. These findings are in accord with our previous results indicating that primary headache sufferers are prone to phantom tooth pain.

Adult↗
PubMed1997

Decentralization monoamine super-sensitivity of migraine and opiate abstinence: common features and different target mechanisms?

The similarity between opiate withdrawal and migraine (M) has been confirmed regarding increased monoamine sensitivity at the neuromuscular junction of the hand's dorsal vein as well as at the neuraxis where dopamine (DA) supersensitivity was observed. Similarities also included an increase in cAMP levels as a precocious sign in both M and opiate withdrawal. Particular attention has been devoted to the time-course of monoamine supersensitivity in M and in abstinence. It has been found that the maximum level of super-sensitivity occurs in M at the end of the M attack, whereas the maximum super-sensitivity is present at the very beginning of opiate abstinence. The inverse time-course of this phenomenon suggests that it could play some pathophysiological role in inducing the end of the M attack. Conversely, it can represent the expected transient result of a pharmacological denervation which ought to result in a supersensitivity of opioid-dependent neuron during withdrawal. In M, the super-sensitivity is wider, indeed, it involves more receptor types. This could be an indirect proof of the involvement of inhibitory pathways other than the opioidergic one.

Adult↗
PubMed1997

The way to serotonergic use and abuse in migraine.

5-HT is currently indicated to play a role in migraine (M). Previously evidenced 5-HT supersensitivity which characterizes M is insufficient to compensate for a possible deficit in 5-HT bioavailability. Inducing a further up-regulation of 5-HT receptor can yield improvement of M syndrome. Chronic treatments of methysergide and propranolol, drugs exerting antagonist action at 5-HT receptors, induced a significant amelioration in 256M sufferers. On the contrary, chronic treatments of ergotamine and sumatriptan, both provided with a 5-HT1 agonist activity, induced a worsening of M in 134 M sufferers. The M worsening was paralleled by an increase in consumption of analgesic drugs. Discussion concerns the effects of the chronically given 5-HT agonists and antagonists as well as the possible receptor mechanism underlying "craving for serotonin" in severe M. The increase of 5-HT supersensitivity evidenced at the end of M attacks is also discussed and its role in determining the interruption of the attack is here suggested.

Adult↗
PubMed1997

Inheritable and acquired hyperalgesia associated to abnormal opioid receptor set-up seem to act as opiate addiction preventors.

Hyperalgesia is known to depend on neuroplastic changes chiefly represented by long-term potentiation. These phenomena are proved to depend on excitatory amino acids (EAAs) action at the level of NMDA receptors. This action is known to be related to nitric oxide (NO) release. We found a visceral/vascular hyperalgesia state in migraine (M) sufferers as well as an inheritable systemic hyperalgesia in healthy subjects who are first-degree consanguineous with M sufferers; this type was labelled 'third hyperalgesia'. We discovered that a hyper-increase of plasma L-citrulline, equimolar co-product in the synthesis of NO, characterizes both M sufferers and their first-degree relatives who are exempt from primary headache. A similar pattern never occurred in healthy subjects having both a personal and family history negative for primary headache. We conclude that both 'third hyperalgesia' and a pattern of NO synthase (NOS) hyperactivity seems to be inheritable and can constitute, at least in part, a ground for developing headache. Morphine, proved to be unable to relieve M attack, was given in low doses that caused pain and side-effects in M sufferers only. This outcome seemingly indicates that M sufferers are characterized by a set-up of opioid receptor subtypes different from that of healthy headache-exempts. Following a period of morphine addiction and a withdrawal period, 65.07% of a group of 63 opiate addicts developed M syndrome. All these subjects were first-degree consanguineous relatives of primary headache sufferers. Discussion topics concern the activity of morphine in NO release and the role of NO in sensory transmission of both controls and hyperalgesia sufferers. It is suggested that the inheritable couple consisting of hyperalgesia and NOS hyperactivity can play some role in setting off the pain occurring following morphine in M sufferers.

Adult↗
PubMed1997

Bradykinin and cerebral circulation: selective non-receptor interaction with histamine and serotonin through the system of nitric oxide.

Bradykinin, histamine and serotonin were the most active physiological agonists in increasing jugular levels of nitric oxide when administered into the left common carotid artery of anaesthetized rabbits. Bradykinin potentiated selectively the effects of histamine and serotonin (but not vice versa) on both nitric oxide and carotid blood flow, without involving activation of specific receptors. Since these effects were demonstrated using doses of the three agonists in the order of their physiological plasma concentrations, it was concluded that cerebral circulation in regulated, also within its autoregulatory limits, by bradykinin through selective autocoidal interactions converging on nitric oxide.

Acetylcholine↗
PubMed1997

Modulation of excitatory amino acids pathway: a possible therapeutic approach to chronic daily headache associated with analgesic drugs abuse.

The use of antagonists of N-methyl-D-aspartate (NMDA) receptors, or the administration of inhibitors of the synthesis or of the release of excitatory amino acids, enables the analgesic drug-dependence associated with chronic daily migraine to be overcome without any physical abstinence sign. Follow-up period indicates that negative modulators of excitatory amino-acid function can induce a stable benefit. The persistent benefit is seemingly due to an inhibitory effect on the process underlying the hyperalgesia state which is a crucial feature of migraine. It can also be suggested that the antagonist activity at NMDA receptor might play a role in very severe non-opioid analgesic drug dependence.

Acetates↗
PubMed1997

Involvement of central cholinergic system in antinociception induced by sumatriptan in mouse.

The antinociceptive effect of the antimigraine drug sumatriptan was assessed in mice (hot-plate and abdominal constriction tests). Antinociception induced by sumatriptan (10-30 mg kg-1 i.p.) was prevented by the muscarinic antagonist atropine (5 mg kg-1 i.p.), the ACh-depletor hemicolinium-3 (1 microgram per mouse i.c.v.) and the 5-HT1A antagonist NAN-190 (0.5 mg kg-1 i.p.). Naloxone, CGP-35348 and reserpine administered in doses suitable for blocking analgesia respectively induced by morphine, baclofen and clomipramine did not modify sumatriptan antinociception. On the basis of the above findings, we can deduce that sumatriptan was able to induce antinociception by increasing cholinergic neurotransmission through the stimulation of 5-HT1A receptors.

Analgesics↗
PubMed1996

Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy.

In this study fibromyalgia sufferers were randomly administered a combination of monoamine-oxidase inhibitors (MAOIs)-A/B with 5-HTP, 5-HTP alone, MAOIs-A/B alone, or the tricyclic drug amitriptyline in order to compare the efficacy of these treatments. The benefits on the painful syndrome were assessed by using Visual Analogic Scale score rating from 0 to 4. The combination of MAOIs with 5-HTP significantly improved fibromyalgia syndrome as determined by Visual Analogic Scale whereas the other treatments yielded poorer benefits. No subject withdrew from the trial due to adverse effects, even if some sleep disturbances and mild stomach-ache were reported. The tolerability of the association MAOIs/5-HTP was good, although a transient cheese effect occurred in one of the patients treated with MAOIs as well as in a patient treated with the association MAOIs and 5-HTP. No one of these two cases was due to pharmacological dietetic mistake of the patient. In both the cases the transient hypertension was associated to very dramatic emotional events. The benefits obtained by using the combination of MAOIs with 5-HTP can be explained with a treatment-induced enhancement of aminergic and serotonergic transmission. The recently shown high prevalence of migraine in the population of fibromyalgia sufferers, suggests a common ground shared by fibromyalgia and migraine. Migraine has been demonstrated to be characterized by a defect in the serotonergic and adrenergic systems. A parallel dramatic failure of serotonergic systems and a defect of adrenergic transmission have been evidenced to affect fibromyalgia sufferers too. Enhancing serotonergic analgesia while increasing adrenergically mediated analgesia seems to be an important tool in fibromyalgia. Treatment consisting with the association MAOIs/5-HTP is aimed at enhancing serotonergic/adrenergic transmission by inducing an up-regulation of serotonergic/adrenergic receptors and a simultaneous increase of serotonin levels in the central nervous system.

5-Hydroxytryptophan↗
PubMed1996

Differential sensitivity to morphine challenge in migraine sufferers and headache-exempt subjects.

The effectiveness of a therapeutic dose of morphine in relieving migraine attacks was compared with placebo. Morphine was no more effective than placebo and provoked severe side effects. When low-dose morphine was administered to normal non-headache controls and migraineurs when headache-free, physical and psychologic reactions were induced only in migraineurs. On pupillometric study, only migraineurs had defective morphine-miosis. It is suggested that the observed clinical phenomena in response to morphine can be explained by differences in expression and sensitivity of some opioid receptor subtypes in migraine.

Adult↗
PubMed1996

The central cholinergic system has a role in the antinociception induced in rodents and guinea pigs by the antimigraine drug sumatriptan.

The antinociceptive effect of the antimigraine drug sumatriptan was assessed in mice and rats (hot-plate, abdominal constriction and paw-pressure tests) and in guinea pigs (paw-pressure test). The ACh extracellular concentration also was detected in the hippocampus of freely moving rats by microdialysis experiments. Antinociception was induced by sumatriptan administered both parenterally (5-10 mg.kg-1 i.v.; 10-30 mg.kg-1 i.p.) and i.c.v. (50-100 micrograms per mouse). Sumatriptan antinociception was potentiated by physostigmine (0.05 mg.kg-1 i.p.) and was prevented by the muscarinic antagonist atropine (5 mg.kg-1 i.p.), the ACh depletor HC-3 (1 micrograms per mouse i.c.v.) and the 5-hydroxytryptamine1A antagonist 1-(2-methoxyphenyl)-4-[4-(2 phthalimido)butyl] piperazine (0.5 mg.kg-1 i.p.). Naloxone, 3-aminopropyl-diethoxy-methyl-phosphinc acid, 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino) ethyl ester and reserpine, administered in doses suitable for blocking analgesi induced by morphine, baclofen, 5-hydroxytryptamine4 agonist and clomipramine, respectively, did not modify sumatriptan antinociception. Sumatriptan, administered in the range of antinociceptive doses, was able to increase the level of ACh present in extracellular hippocampal space. On the basis of these findings we can deduce that sumatriptan was able to induce antinociception by increasing cholinergic activation in the CNS. Such activation, as indicated by the antagonism exerted by 1-(2-methoxyl-phenyl)-4-[4-(2 pethalimido)butyl]piperazine, may depend on stimulation of 5-hydroxytryptamine1A autoreceptors. It remains to be clarified whether the antimigraine activity of sumatriptan in humans is totally dependent on cranial vessel vasoconstriction of whether its central cholinergic antinociception also plays a role.

Acetylcholine↗
PubMed1995

Exploration of NMDA receptors in migraine: therapeutic and theoretic implications.

Pain intensity was observed before and after the subcutaneous (s.c.) administration of ketamine hydrochloride (80 micrograms/kg/s.c.) or saline (0.9% NaCl given by the same route) in 17 migraine (M) sufferers as an acute treatment of their M attacks. The same parameter was observed in another group of 17 M-sufferers complaining of very severe and frequent M attacks; these subjects were completely refractory to the prophylactic treatments currently used in M. In this second group, ketamine 80 micrograms/kg/s.c./three times a day) or saline was randomly assigned in a short (3-week) chronic treatment. A randomized, double-blind, cross-over study design was used both when testing ketamine as an acute administration for relieving M attack and when comparing its effect to that of the placebo in a chronic treatment for preventing M-pain. Ketamine, but not placebo, produced a marked relief of pain both as an acute treatment and as a prophylactic therapy. Mild specific side-effects were observed in the majority of the patients treated with ketamine. Moreover in the placebo group, the majority of these patients also complained of side-effects. The present results support the hypothesis that N-methyl-D-aspartic acid (NMDA) receptors play an important role in the mechanisms of M.

Adult↗
PubMed1994

Nostril capsaicin application as a model of trigeminal primary sensory neuronal activation.

Capsaicin was applied unilaterally to the nostril mucosa of 18 episodic cluster headache sufferers in remission. Plasma and saliva levels of substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay. Increase of salivary SP-LI and CGRP-LI as well as of plasma CGRP-LI occurred after capsaicin stimulation. Capsaicin-induced neurochemical changes in saliva and in plasma were compared to the changes observed during cluster headache attacks measured in a separate study. The comparative changes in SP, CGRP and VIP characterizing these two conditions suggest that trigeminal capsaicin-sensitive sensory neurones are unlikely to play any fundamental role in the mechanics of cluster headache.

Administration, Intranasal↗
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↗