Biomedical subjects

M Nicolodi

Publications and source records attributed to M Nicolodi.

40 records · Page 3Linked to original sources

PubMedDate not supplied

Central cholinergic challenging of migraine by testing second-generation anticholinesterase drugs.

The antinociceptive activity of donepezil, a novel cholinesterase inhibitor, was investigated in the mouse hot plate test. Donepezil (5 to 10 mg kg(-1) i.p.) induced a dose-dependent antinociception that reached its maximum effect 15 minutes after injection. Donepezil antinociception was prevented by the antimuscarinic drug scopolamine. At analgesic doses, donepezil did not alter gross animal behavior. These results indicate that donepezil is endowed by muscarinic antinociceptive properties, suggesting this compound as a potential therapeutic approach for the treatment of painful pathologies. Therefore, we investigated donepezil's effect in migraine. Donepezil (5 mg per os, evening assumption) was effective as a prophylatic agent in patients suffering from migraine with or without aura by reducing the number of hours with pain, the number of attacks, and the severity of the pain attack. The efficacy of donepezil was compared with that of the beta-blocker propranolol (40 mg bid per os), showing higher activity. Response rates of a large-sized open study devoid of entry criteria regarding migraine subtypes suggest the drug as an excellent prophylactic compound for migraine in general practice. Clinical results also indicate that the activation of the cholinergic system can represent a novel prophylactic approach to migraine.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

[Noci-autonomic-affective automatism, the physiopathological essence of hemicrania. The serotonin theory as a guiding principle in the labyrinth of interpretations].

After thousands of painful long-lasting migraine or extremely violent cluster headache attacks no one has yet traced histological inflammatory or degenerative alterations of the interested tissues able to explain such dreadful pain. Therefore it has seemed logical to include these pains among the unjustified aimless, non finalized types of pain. Furthermore, clinical characteristics of automatism, explosiveness and the course of these pains resemble other aimless pains like those of organic deafferentation (phantom pain) which appear in a desensitized limb after denervation or even in amputated subjects. Intense and long lasting pains in opioid abstinence, mainly located in the chest and in the hip, also have all the characteristics of aimless pain. Idiopathic cephalic pain, together with deafferentation or opioid-abstinence pain, seems to be due to a dysafferentation which, through different channels, follows an analogous mechanism. This mechanism seems to be due to a deficit of autoanalgesia which in both organic deafferentation (phantom limb) and in opioid-abstinence can be related to the disuse of afferences' modulation. In idiopathic headache such a failure of autoanalgesia is likely to be due to a genetic, idiopathic mechanism. Headaches are characterized by a clear deficiency of autoanalgesia which may manifest itself not only at the level of the cephalic segment, which is so rich in afferences, but it may even involve the whole body. Even if pain is the compulsory phenomenon to diagnose headache, one must consider that migraine is a symptomatic triad in which vegetative and emotional phenomena also emerge. These phenomena are interindependent and not interdependent as each of them may appear as a first manifestation of an attack; one must therefore consider the possibility of a "unicum movens". Serotonin was taken into consideration because of its action which interests all or nearly all vegetative-emotional pain transmitting pathways. Today's identification of four types and various sub-types of 5-HT receptors has revealed the extraordinary eclecticism of this transmitter which within migraine's clinical expression underscores that migraine sufferers are characterized by a marked sensitivity to all the drugs capable of acutely or chronically interacting with serotonin metabolism and binding with many serotonin receptor types and sub-types. So even if the migraine sphinx still proposes its enigma, researchers--with their incurable curiosity--may not only find more and more accurate and effective medication for many human beings but also start penetrating a mystery, a great challenge to human imagination.

Adult↗

PubMedDate not supplied

Non-vascular action of calcium blockers in migraine: pupillopharmacological study.

A pupillopharmacological study has been carried out to evaluate the influence of two calcium blockers (CBs), flunarizine and nimodipine, on iris neurotransmission in migraine patients. Pretreatment with an oral dose of flunarizine or nimodipine markedly decreased the mydriasis induced by instillation of tyramine, a noradrenaline releaser. On the contrary, both drugs did not change the mydriasis by conjunctival phenylephrine, a postsynaptic adrenoceptor stimulant. In addition, nimodipine abolished the miosis caused by echothiophate iodide eye drops, a putative releaser of substance P from trigeminal sensory nerve endings. These findings suggest the idea that CBs treatment in migraine syndromes acts at presynaptic level by attenuating calcium-dependent release of monoaminergic and peptidergic neurotransmitters.

Echothiophate Iodide↗

PubMedDate not supplied

Electroencephalographic alterations in migraine as an expression of "self-deafferentation": a hypothesis.

The deafferentation of a leg in animal is followed by: local analgesia; generation in spinal cord and brainstem (along the sensitive fibers of second order) of quasi epileptic foci emitting continuously and/or in bursts, epileptic-like discharges; scratching, attacks and finally autocannibalism of the deafferentated arm. This perverted behavior (autotomy) is attributed to an emission from the quasi epileptic foci of pain signals projected to deafferentated regions by cognitive sites of consciousness. The quasi epileptic foci, generating bursts of "automatic" pain, are considered the basic mechanism of pain in deafferentated and amputated humans. The nature of pain in migraine is assumed here as an analog to the mechanism of organic deafferentation; a generation in the brainstem of nociceptive foci, with the head as main projection. The enigmatic epileptic-epileptoid characteristics of EEG in migraineurs could be an expression of the electrically hyperactive "quasi epileptic foci" located mainly within the brainstem and generated by the insufficient opioid inhibition of sP-ergic neurons.

Animals↗