1,721,235 research outputs found

    Geppetti, P.

    No full text

    Relative contribution of sympathetic and sensory nerves to thermal nociception and tissue trophism in rats

    No full text
    Neonatal injection of 6-hydroxydopamine (420 mg/kg s.c.) lowered thermal nociceptive threshold (hot plate and tail immersion tests) and increased levels of substance P-like immunoreactivity in the skin (paws, tail, area of vibrissae) of Wistar rats. Chemical ablation of primary afferents, induced in either neonatal or adult rats by systemic administration of capsaicin, increased thermal nociceptive threshold (hot plate), irrespective of 6-hydroxydopamine pretreatment and reduced substance P-Iike immunoreactivity in the hind-paw skin of either control or sympathectomized rats. Capsaicin pretreatment of neonatal but not adult rats produced antinociceptive effect in the tail-immersion test and completely reversed the hyperalgesic effect of sympathectomy, without affecting levels of substance P-like immunoreactivity in the tail skin. These findings indicate that sympathetic nerves and different subsets of capsaicin-sensitive primary afferents are involved in the processing of thermal nociceptive input. Corneal and cutaneous lesions were induced by neonatal sensory denervation with capsaicin. Sympathectomy afforded protection against the development of corneal pathology, while it did not affect the occurrence of cutaneous lesions. It appears that a balance in the neuronal activity between sympathetic neurons and trigeminal sensory neurons is critical for maintaining the normal trophism of the cornea, and that sensory neuropeptides play a key role in the maintenance of normal trophism of the skin

    Age-related changes in substance P and vasoactive intestinal polypeptide immunoreactivity in the rat stomach and small intestine.

    No full text
    Immunoreactivity for substance P (SP-LI) and vasoactive intestinal polypeptide (VIP-LI) in the stomach, duodenum, jejunum and ileum of young (3-month-old), adult (12-month-old) and old (28-month-old) male Wistar rats were determined by radioimmunoassay. SP-LI and VIP-LI did not show changes in the stomach or in the small intestine portions investigated in adult in comparison with young rats. In old rats SP-LI levels were unchanged in the stomach and in the duodenum, reduced in the jejunum and increased in the ileum. VIP-LI concentrations were unchanged in the stomach, and remarkably reduced in the duodenum, jejunum and ileum of old rats. Since the two neuropeptides investigated are localized primarily within different intrinsic gastrointestinal neurons, the present findings suggest that the various populations of gastrointestinal neurons are affected in a different manner during aging

    Ketones and pain: unexplored role of hydroxyl carboxylic acid receptor type 2 in the pathophysiology of neuropathic pain.

    No full text
    The mechanisms underlying neuropathic pain are poorly understood. Here we show the unexplored role of the hydroxyl carboxylic acid receptor type 2 (HCAR2) in 2 models of neuropathic pain. We used an oral treatment with dimethyl fumarate and the HCAR2 endogenous ligand -hydroxybutyrate (BHB) in wild-type (WT) and HCAR2-null mice. We found an up-regulation of the HCAR2 in the sciatic nerve and the dorsal root ganglia in neuropathic mice. Accordingly, acute and chronic treatment with dimethylfumarate (DMF) and BHB reduced the tactile allodynia. This effect was completely lost in the HCAR2-null mice after a 2-d starvation protocol, in which the BHB reached the concentration able to activate the HCAR2-reduced tactile allodynia in female WT mice, but not in the HCAR2-null mice. Finally, we showed that chronic treatment with DMF reduced the firing of the ON cells (cells responding with an excitation after noxious stimulation) of the rostral ventromedial medulla. Our results pave the way for investigating the mechanisms by which HCAR2 regulates neuropathic pain plasticity.Boccella, S., Guida, F., De Logu, F., De Gregorio, D., Mazzitelli, M., Belardo, C., Iannotta, M., Serra, N., Nassini, R., de Novellis, V., Geppetti, P., Maione, S., Luongo, L. Ketones and pain: unexplored role of hydroxyl carboxylic acid receptor type 2 in the pathophysiology of neuropathic pain

    Preparation of sulfamoylphenyl thiourea derivatives as vanilloid TRPV1 receptor antagonists for the treatment of inflammatory states.

    No full text
    Title compds. I [wherein R1 = H; R2 = (un)substituted benzyl or 2-phenylethyl; R3 = H, halo or alkoxy; R4 = (CH2)nNH; n = 0-3; R5 = O or S; R6 = NHCH2; R7 = t-Bu or CF3] were prepd. as vanilloid TRPV1 receptor antagonists. For instance, thiourea II was synthesized in 42% yield by nucleophilic addn. of 4-tert-butylbenzyl isothiocyanate with the corresponding sulfamoylaniline (prepn. given). II was found to inhibit TRPV1-dependent responses with an affinity that was significantly greater than that of the classic TRPV1 receptor antagonist, capsazepine, in both in vitro and in vivo studies. Therefore, I can be used for the prepn. of medicaments for the treatment of inflammatory states

    Preparation of benzylthiourea derivatives as vanilloid TRPV1 receptor antagonists.

    No full text
    The title compds. I [R = F, Cl, etc.; R1 = H, F, Cl, etc.; R2 = tert-Bu, CF3; n = 0, 1 or 2; X = O, S] are prepd. I [R = iodo; R1 = H; R2 = tert-butyl; n = 1] (prepd. in a multistep process from 4-hydroxy-3-methoxybenzylamine hydrochloride) significantly reduced capsaicin-induced wiping in rats

    Capsaicin-sensitive afferents and pain arising from the urinary bladder.

    No full text
    The use of capsaicin has allowed important advances in understanding the physiological and pathophysiological roles of the sensory innervation of the bladder and urethra. For the first time, a prototype drug is available that allows selective pahrmacological manipulation of bladder sensory nerves. Major roles of these primary afferents are the signaling of pain arising from the bladder and the production of neurogenic inflammation. Available evidence indicates that capsaicin-sensitive afferents are present in the human urinary bladder. It is expected that capsaicin itself or its analogs will be of great value for diagnostic and therapeutic purposes in the urological field and particularly for treatment of painful disorders of the lower urinary tract

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Full text link
    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
    corecore