569 research outputs found
CEP889351 Supplemetal Material2 - Supplemental material for Epidemiology and determinants of chronic migraine: A real-world cohort study, with nested case-control analysis, in primary care in Italy
No full textSupplemental material, CEP889351 Supplemetal Material2 for Epidemiology and determinants of chronic migraine: A real-world cohort study, with nested case-control analysis, in primary care in Italy by Ettore Marconi, Serena Pecchioli, Mihaela Nica, Delia Colombo, Francesco Mazzoleni, Francesco De Cesaris, Pierangelo Geppetti, Claudio Cricelli and Francesco Lapi in Cephalalgia</p
CEP889351 Supplemetal Material1 - Supplemental material for Epidemiology and determinants of chronic migraine: A real-world cohort study, with nested case-control analysis, in primary care in Italy
No full textSupplemental material, CEP889351 Supplemetal Material1 for Epidemiology and determinants of chronic migraine: A real-world cohort study, with nested case-control analysis, in primary care in Italy by Ettore Marconi, Serena Pecchioli, Mihaela Nica, Delia Colombo, Francesco Mazzoleni, Francesco De Cesaris, Pierangelo Geppetti, Claudio Cricelli and Francesco Lapi in Cephalalgia</p
SULFONAMIDO COMPOUNDS THAT ANTAGONISE THE VANILLOID TRPV1 RECEPTOR
No full textThe invention relates to sulfonamido derivatives of formula (I) ##STR00001## wherein R.sub.1-R.sub.7 are as defined in the description. Compounds (I) antagonize the vanilloid receptor and can be used for the preparation of medicaments for the treatment of inflammatory states
Ruolo dei recettori attivati dalle proteasi nell'infiammazione cronica e nel rimodellamento tissutale nel sistema cardiovascolare erespiratorio
No full textSULFONAMIDO COMPOUNDS THAT ANTAGONISE THE VANILLOID TRPV1 RECEPTOR
No full textThe present invention relates to antagonists of the vanilloid receptor, in particular to sulfonamido derivatives that antagonize the TRPV1 receptor
Substance P stimulates neovascularization in vivo and proliferation of cultured endothelial cells
No full textWe have investigated the possible effect of substance P (SP), a main mediator of neurogenic inflammation, on the growth of capillary vessels in vivo, and on the proliferation of cultured endothelial cells in vitro. Slow release preparations of SP were implanted into the avascular cornea of New Zealand White rabbits and vessel growth was monitored daily through a slit lamp stereomicroscope. SP (1-5 micrograms/pellet) induced a marked neovascularization. A selective NK-1 receptor agonist [beta-Ala4, Sar9, Met(O2)11]-SP(4-11) also induced neovascularization. The addition of SP to serum-free cultured endothelial cells, isolated from bovine adrenals (BACE) and from human umbilical cord veins (HUVE), increased proliferation of both cell lines in a concentration-dependent manner with maximal activity at 10(-8) M (BACE) and 10(-10) M (HUVE). The selective NK-1 receptor agonist induced a similar proliferative action on both cell lines, while the selective NK-2 receptor agonist [beta-Ala8]-NKA(4-10) and the selective NK-3 receptor agonist [MePhe7]-NKB had no significant effect. Two different SP antagonists [D-Pro2, D-Trp7,9]-SP and [D-Pro4, D-Trp7,9,Phe11]-SP (4-11) blocked the response to SP. These findings indicate that SP can directly stimulate the process of neovascularization, probably through induction of endothelial cell proliferation. This hitherto unraveled activity of SP could play a key role in the trophic action produced by activation of the efferent function of peripheral endings of primary sensory neurons
Contribution of peripheral endothelin ET(A) and ET(B) receptors in neuropathic pain induced by spinal nerve ligation in rats
No full textEndothelins (ETs) contribute to the sensory changes seen in animals models of inflammatory, cancer and diabetic neuropathic pain, but little is known about their nociceptive role following peripheral nerve injury. The current study evaluated mechanisms by which ETs can drive changes in nociceptive responses to thermal stimulation of the hind paw of rats induced by unilateral lumbar L5/L6 spinal nerve ligation (SNL) injury. SNL sensitizes rats to acetone-evoked cooling of and radiant heat application (Hargreaves test) to the ipsilateral hind paw (throughout 3-40 and 9-40days after surgery, respectively). At 12days after SNL, intraplantar (i.pl.) injection of endothelin-1 (ET-1, 10pmol) induces greater overt nociception that was reduced only by treatment with the selective ET(A) peptidic antagonist (BQ-123, 10nmol, i.pl), but unchanged by the selective ET(B) peptidic antagonist (BQ-788). Cold allodynia evoked by cooling the ipsilateral hind paw with acetone was reduced by i.pl. injection of both antagonists BQ-123 or BQ-788 (3 or 10nmol). In contrast, heat hyperalgesia evaluated by Hargreaves method was reduced only by BQ-123. SNL enhanced the [Ca(+2)](i) increases induced by ET-1 (100nM) in neurons from L5/L6 (injured) and L4 (intact) cultured dorsal root ganglion, but did not change the responses of non-neuronal cells. Furthermore, Western blot analysis revealed that SNL increased ET(A) and ET(B) receptor protein expression in spinal nerves. Thus, SNL induces marked hind paw hypersensitivity to thermal stimulation in part via up-regulation of peripheral sensory nerve pronociceptive ET(A) and ET(B) receptor-operated mechanisms. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved
O-SUBSTITUTED-DIBENZYL UREA-DERIVATIVES AS TRPV1 RECEPTOR ANTAGONISTS
No full textThe invention relates to compounds of formula (I) wherein R is halogen; R 1 is selected from 2-hydroxyethyl, 2,3-dihydroxypropyl, 3-hydroxypropyl, 2,2-dihydroxyethyl, 3,3-dihydroxypropyl, aminomethyl, 2-aminoethyl, 3-aminopropyl, 3-amino-2-hydroxypropyl, ..
The effect of thiorphan on release of sensory neuropeptides from guinea-pig cerebral venous sinuses
No full textThe effect of peptidase inhibitors on neuropeptide release from peripheral endings of capsaicin-sensitive sensory neurons was studied in cerebral superior sagittal and transverse sinuses of guinea-pig. Capsaicin (1 microM)-evoked release of substance P-like immunoreactivity (SP-LI) was increased in a concentration-dependent manner by thiorphan (0.1-10 microM). Captopril (10 microM) or a mixture of bestatin (10 microM), leupeptin (10 microM) and bacitracin (10 microM) did not affect the capsaicin-evoked SP-LI release. Thiorphan (10 microM) increased also the capsaicin-evoked release of neurokinin A-like immunoreactivity (TK-LI) and calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) by 228\% and 172\%, respectively, while captopril (10 microM) was without effect. Thiorphan (10 microM), but not captopril (10 microM), enhanced by 239\% CGRP-LI release induced by bradykinin (10 microM). In the cerebral venous vessels neutral endopeptidase (EC 3.4.24.11, NEP)-like activity was 58.8 +/- 6.1 pmol/mg protein/min, while angiotensin converting enzyme-like activity was below the detection limit of the assay. A thiorphan-sensitive mechanism, putatively attributable to NEP, plays a major role in the inactivation of peptides released from or acting on capsaicin-sensitive sensory fibres of cerebral venous sinuses of guinea-pig
Migraine Treatment: Towards New Pharmacological Targets
No full textMigraine is a debilitating neurological condition affecting millions of people worldwide. Until a few years ago, preventive migraine treatments were based on molecules with pleiotropic targets, developed for other indications, and discovered by serendipity to be effective in migraine prevention, although often burdened by tolerability issues leading to low adherence. However, the progresses in unravelling the migraine pathophysiology allowed identifying novel putative targets as calcitonin gene-related peptide (CGRP). Nevertheless, despite the revolution brought by CGRP monoclonal antibodies and gepants, a significant percentage of patients still remains burdened by an unsatisfactory response, suggesting that other pathways may play a critical role, with an extent of involvement varying among different migraine patients. Specifically, neuropeptides of the CGRP family, such as adrenomedullin and amylin; molecules of the secretin family, such as pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP); receptors, such as transient receptor potential (TRP) channels; intracellular downstream determinants, such as potassium channels, but also the opioid system and the purinergic pathway, have been suggested to be involved in migraine pathophysiology. The present review provides an overview of these pathways, highlighting, based on preclinical and clinical evidence, as well as provocative studies, their potential role as future targets for migraine preventive treatment
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