Biomedical subjects

M Alessandri

Publications and source records attributed to M Alessandri.

At least 37 records · Page 2Linked to original sources

PubMed1991

Low pH medium induces calcium dependent release of CGRP from sensory nerves of guinea-pig dural venous sinuses.

Low pH medium has been shown to activate the 'efferent' function of capsaicin-sensitive primary sensory neurons. Calcitonin gene-related peptide (CGRP) is released from capsaicin-sensitive afferents of guinea-pig superior sagittal and transverse sinuses (SSTS), by capsaicin or bradykinin. Here, we report that low pH medium produces a remarkable release of CGRP from SSTS, which was dependent on the concentration of hydrogen ions of the medium (pH 7-5). Moreover, the pH 5-evoked release of CGRP-LI was markedly reduced (by about 70%) in a calcium-free medium containing 1 mM EDTA or abolished in samples pre-exposed to 10 microM capsaicin. The present observation that lowering of the pH promotes release of a powerful vasoactive peptide from perivascular capsaicin-sensitive sensory nerves may have some relevance in the pathophysiology of brain injury and migraine headaches.

Animals↗

PubMed1991

In vivo pupillary constrictor effects of substance P in man.

The ocular effects of substance P (SP) were studied in 13 normal volunteers. Various concentrations of SP (0.135, 1.35 and 135 micrograms per 100 microliters) were instilled into the conjunctival sac and pupillary area changes were evaluated by means of an electronic pupillometer. The ability of SP to modify the mydriasis induced by pretreatment with 1% homatropine eyedrops was also studied. The instillation of SP produced miosis in a dose-dependent manner without provoking any ocular disturbances. Furthermore, the highest concentration tested was unable to reduce the homatropine-induced mydriasis. These findings indicate that SP exerts a pupillokinetic action in humans which probably occurs via a receptor mechanism. Since muscarinic blockade is not overcome by the peptide instillation, the results do not clarify whether SP causes miosis acting on iris muscles and/or cholinergic fibres.

Adult↗

PubMed1991

Evidence for alpha 1-adrenoreceptor hyperresponsiveness in hypotensive cirrhotic patients with ascites.

Cirrhosis with ascites is often characterized by arterial hypotension associated with increased plasma norepinephrine levels. Clinical evidence suggests a decreased sensitivity to norepinephrine in this clinical setting, indicating a potential derangement of alpha 1 adrenoreceptors. The aim of the present study was to evaluate the reactivity of the alpha 1-adrenoreceptor, using phenylephrine, a selective alpha 1 receptor agonist. First, we evaluated the pupillar response to the intraconjunctival administration of the agonist. Hypotensive cirrhotic patients showed a trend to a more marked and prolonged response, compared with age-matched healthy controls. Second, we studied the response of alpha 1-adrenoreceptors in the peripheral vasculature by administering iv phenylephrine to a similar group of patients. A significantly greater and longer lasting pressor response was observed in hypotensive cirrhotic patients (p less than 0.0001 vs. healthy controls). Our results indicate that in this group of patients, there is a rather peculiar situation, characterized by alpha 1-adrenoreceptor hyperresponsiveness in the presence of high levels of circulating norepinephrine. This finding could be related to biochemical abnormalities within the peripheral sympathetic nervous system endings.

Adult↗

PubMed1990

Transcutaneous electrical stimulation applied to the infratrochlear nerve induces a homatropine-resistant miosis in humans.

1. Both high- and low-intensity transcutaneous electrical stimuli were applied to the emergence of the infratrochlear nerve in 18 healthy subjects. The effect on the size of the homolateral pupil was investigated. The width of the pupil was also measured when high-intensity transcutaneous electrical stimulation was applied to the contralateral side. 2. The high-intensity pulse resulted in constriction of the pupil when the stimulation was homolateral. The miosis was slow in onset (120 s latency) and long-lasting (80 s). No pupillary changes were detected after either ipsilateral low-intensity or contralateral high-intensity stimuli. 3. In 11 healthy subjects, the pupillary response to transcutaneous electrical stimulation was evaluated during iris parasympathetic blockade induced by homatropine eyedrops. The disappearance of the light reflex due to homatropine was considered an index of the parasympathetic blockade. Afterwards, a high-intensity pulse was transcutaneously delivered to the emergence of the infratrochlear nerve and the ipsilateral pupil size was measured. 4. A reduction in the pupillary size followed the electrical stimulation, still under the effect of homatropine which abolished the light reflex. The time course of this pupillary constriction was similar to that seen without the influence of homatropine. 5. The findings suggest that homolateral miosis, observed after unilateral high-intensity stimulation of the infratrochlear nerve, does not stem from cholinergic activation. It has been suggested that miosis induced by transcutaneous electrical stimulation may be due to an antidromic activation of the iris sensory fibres.

Adult↗

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↗

PubMed1990

Teaching youths with autism to offer assistance.

Three adolescent boys with autism were taught to offer assistance to a person stating inability to complete a task. The study used a multiple baseline across the 3 youths and a multiple baseline across three tasks for each student. Both designs provided clear support for the ability of the youths to discriminate those settings in which offers of assistance were desired. All 3 participants showed relatively rapid acquisition of responding. Generalization was assessed to a new person in the training setting, to a familiar person in a new room at the center, to the mother in the youth's home, and to three novel tasks. Generalization to a new person in the familiar setting was most likely to occur, with very high levels of responding for all 3 youths. Generalization to the other conditions varied across youths, although all 3 boys showed some transfer of skills to all conditions.

Adolescent↗

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

The pressor hyperresponsiveness to phenylephrine unmasks sympathetic hypofunction in migraine.

The pressor responsiveness to phenylephrine, an almost pure agonist of peripheral alpha-1-adrenoceptors, was studied in 32 migraine patients in headache-free intervals. Eighteen healthy volunteers served as a control group. Fourteen patients and 14 controls also underwent the tilt test. The following observations were made: (1) the pressor response to phenylephrine was significantly greater and longer lasting in patients than in controls; (2) the reflex decrease of heart rate did not differ in the two groups; (3) a normal orthostatic increase of blood pressure and heart rate occurred in migraineurs with hyperresponsiveness to phenylephrine. These findings suggest a supersensitivity of vascular adrenoceptors which is compatible with a chronic adrenergic deficiency in migraineurs. Since patients did not show an orthostatic hypotension in attack-free periods, the compensatory character of receptoral supersensitivity and the possible mechanisms of cardiovascular dysautonomia, which may occur during migraineous attack, were discussed.

Adult↗

PubMed1988

The contribution of capsaicin-sensitive sensory nerves to xylene-induced visceral pain in conscious, freely moving rats.

1. Intravesical instillation of xylene (10-100%, dissolved in silicone oil) through a catheter implanted into the bladder of conscious, freely-moving rats produced behavioural effects (licking of lower abdomen or perineal region) suggestive of intense visceral pain, not mimicked by topical application of the irritant on the urethral outlet. 2. The xylene-induced visceral pain was prevented, to the same extent, by systemic desensitization to capsaicin (50 mg/kg s.c.) performed in either adult or newborn rats, as well as by extrinsic bladder denervation (pelvic ganglionectomy), thus indicating the involvement of primary afferents in the bladder wall. 3. Other behavioural responses induced by xylene instillation into the bladder (hind limb hyperextension, grooming) were not affected by systemic capsaicin desensitization in either adult or newborn rats, but were abolished by bladder denervation. 4. Systemic capsaicin desensitization produced an almost complete depletion of substance P-, neurokinin A-like and calcitonin gene-related peptide-like immunoreactivity in the rat urinary bladder. 5. These findings indicate that, in addition to their role in activating reflex micturition, the neuropeptides-containing capsaicin-sensitive sensory nerves of the rat bladder are involved in chemogenic visceral pain.

Aging↗

PubMed1988

Capsaicin-sensitive tachykinin-like immunoreactivity in the thymus of rats and guinea-pigs.

Capsaicin-sensitive, substance P-like immunoreactivity (SP-LI) has been detected recently in rat thymus. Other tachykinins are frequently present with SP. In the present study, tachykinin-like immunoreactivity (TK-LI) was measured in guinea-pig, rat, mouse and hamster thymus with the amount detectable being greatest in guinea-pig, less in rat and least in mouse; it was not detectable in hamsters. In guinea-pig and rat thymus, but not in mouse, TK-LI was markedly reduced by pretreatment with capsaicin. TK-LI levels correlated significantly with those of SP-LI in both guinea-pig and rat thymus. High-performance liquid chromatography (HPLC) fractions considered to represent neurokinin A, eledoisin and neuropeptide K were present in guinea-pig thymus but only the first two were present in rat thymus.

Animals↗

PubMed1988

Does anisocoria by clonidine reflect a central sympathetic dysfunction in cluster headache?

Local pharmacological manipulations of both pupils in persons with cluster headache (CH) have shown a reduced pain-side sympathetic activity. It is difficult to determine if this sympathetic defect is localized in the nuclei of the CNS and/or in peripheral neurons that innervate the pupil. This study demonstrates that in a CH group 2% tyramine (an intraneuronal norepinephrine releaser) instillation into both eyes induces an asymmetric and bilateral mydriasis with the onset of anisocoria characterized by a pupillary diameter being less on the pain-side eye. In addition, intravenous administration of 0.10 mg clonidine, an inhibitor of central sympathetic activity, causes a bilateral miotic response, which is more marked on the pain-side eye. In a healthy control group, clonidine induces a symmetric and bilateral miosis but less intense than that observed in both eyes of CH sufferers. In CH patients, pretreatment with clonidine augments the degree of anisocoria induced by tyramine instillation, increasing the mydriatic response only in the pain-free-side pupil. The hypothesis of a permanent sympathetic defect of the pain-side pupil expressing itself as a reduced sympathetic tone of CNS nuclei and peripheral neurons that innervate the pupil is proposed.

Adult↗

PubMed1987