Showing papers by "Cristina Tassorelli published in 2008"

Role of calcitonin gene-related peptide and substance P in different models of pain

Abstract: Calcitonin gene-related peptide (CGRP) and substance P (SP) play an important role in the development of pain and hyperalgesia. Experimental models have demonstrated that nitroglycerin (NTG)--a nitric oxide donor--provokes a hyperalgesic state, probably via the activation of second-order neurons in the nucleus trigeminalis caudalis. In order to gain further insight into the role of CGRP and SP in different types of experimental pain, we evaluated and compared changes in immunoreactivity (-ir) for these two neuropeptides at different levels of the central nervous system [nucleus trigeminalis caudalis (NTC) and dorsal horns of the lumbar spinal cord] in two animal models of hyperalgesia: systemic NTG administration and formalin test. Following NTG administration, CGRP-ir decreased steadily in the NTC, whereas SP-ir increased transiently. In the lumbar dorsal horns, NTG induced a decrease in SP-ir 1 h after its administration. Formalin injection induced an ipsilateral increase in both CGRP and SP immunostaining at 1 and 2 h in the lumbar dorsal horns. In the NTC, a significant decrease in CGRP-ir was observed at 1 h. The changes in the staining intensities were paralleled by changes in the numbers of CGRP and of SP varicosities in both the NTC and the lumbar dorsal horns. These findings show specific changes in CGRP and SP at different levels of the central nervous system in the different models of pain. In the case of the formalin test, the changes involve both neuropeptides synchronously and to the same extent, whereas in the case of NTG administration, CGRP seems to play a more prevalent and long-lasting role, particularly at the NTC level.

Modulation of pro-survival and death-associated pathways under retinal ischemia/reperfusion: effects of NMDA receptor blockade.

Abstract: Loss of retinal ganglion cells occurs in a variety of pathological conditions, including central retinal artery occlusion, diabetes and glaucoma. Using an experimental model of retinal ischemia induced by transiently raise the intraocular pressure (IOP), In this study, we report the original observation that ischemic retinal ganglion cells death is associated with the transient deactivation of the pro-survival kinase Akt and activation of GSK-3beta followed, during reperfusion, by a longer lasting, PI3K-dependent, activation of Akt and phosphorylation of GSK-3beta. Under these experimental conditions, retinal ischemia induced the expression of Bad, a pro-apoptotic protein, member of the Bcl-2 family. The detrimental effects yielded by the ischemic stimulus were minimized by intravitreal administration of the NMDA receptor antagonist, MK801, that reduced the expression of Bad and significantly increased Akt phosphorylation. In conclusion, our present results contribute to unravel the mechanisms underlying retinal damage by high IOP-induced transient ischemia in rat. In addition, these data implicate the pro-survival PI3K/Akt pathway and the observed reduced expression of Bad in the neuroprotection afforded by MK801.

Dysphagia in multiple sclerosis: from pathogenesis to diagnosis.

Abstract: Abnormalities of swallowing are commonly encountered in Multiple Sclerosis (MS), especially in the most disabled patients. The disturbances usually involve oral and pharyngeal phases of swallowing, although upper oesophageal sphincter dysfunction has also been detected. MS patients need to be effectively evaluated and managed in order to recognize dysphagia before any medical complications such as aspiration pneumonia appear. An integrated approach is proposed to define the severity of dysphagia and to devise the most appropriate therapeutic/rehabilitative methodology.

Reduced habituation of trigeminal reflexes in patients with episodic cluster headache during cluster period.

Abstract: A growing body of evidence supports the pivotal role of the hypothalamus in the pathophysiology of cluster headache (CH). On the basis of animal studies, it has been suggested that a hypothalamic dysfunction can lead to a habituation deficit of brainstem reflex responses, as result of a stress-like condition. Taking into account these findings, we tested the hypothesis that habituation of brainstem reflexes may be impaired in CH patients. The habituation phenomenon of the late components (R2 and R3) of the blink reflex was studied in 27 CH patients during the cluster period, in 22 migraine patients interictally and in 20 control subjects. A significant habituation deficit in the R2 and R3 components was found in CH compared with both controls and migraineurs. The lack of habituation in CH, more pronounced than in migraine, points to abnormal processing of sensory stimuli at the trigeminal level that could be driven by hypothalamic dysfunction during the cluster period.

The Usefulness and Applicability of a Basic Headache Diary Before First Consultation: Results of a Pilot Study Conducted In Two Centres

Abstract: We tested the usefulness and applicability of a simplified headache diary in the diagnosis of migraine (M), tension-type headache (TTH) and medication overuse headache (MOH). The diary was given to headache patients before their first consultation at the headache centre. Seventy-six naive headache patients completed the study. Their understanding of the diary proved highly satisfactory. The patients' level of compliance was also good, with 71% returning the diary completely filled in. The data entered in the diary were deemed complete for the diagnostic purpose in 93% of cases. The level of agreement between headache information gathered through clinical interview and the headache diary was satisfactory. When comparing the diary with the clinical interview, sensitivity was 92% for M, 75% for TTH and MOH. Specificity was 58% for M and TTH, 87% for MOH. Combined use of a diagnostic diary and clinical interview is recommended from the first consultation for headache.

Lack of trigemino-cervical reflexes in progressive supranuclear palsy.

Abstract: Trigemino-cervical reflexes (TCRs) are multisynaptic neck muscle withdrawal responses that are clearly identifiable in humans. Mediated by neural circuits at brainstem level, these reflex responses have been found to be significantly impaired in patients with Parkinson's disease (PD), and it has been hypothesized that a degeneration of brainstem neural structures could play a role in these abnormalities. Because extensive neuronal degeneration at brainstem level has been demonstrated in progressive supranuclear palsy (PSP), in this pilot study we evaluated the TCR responses in 12 subjects with PSP, and in 16 healthy controls. The TCRs were absent in 11 out of the 12 PSP patients while clear responses were evoked in all the healthy subjects. These findings indicate that PSP patients are unable to react to the painful stimuli to the face, suggesting a generalized impairment of the brainstem circuits mediating TCRs.