Palmitoylethanolamide reduces formalin-induced neuropathic-like behaviour through spinal glial/microglial phenotypical changes in mice.

Palmitoylethanolamide (PEA) is an endogenous cannabinoid-like compound in the central nervous system, which can modulate several functions in different pathological states, such as inflammation and pain response. We have here investigated the effect of PEA (5-10 mg/kg, intraperitoneally) on mechanical allodynia and thermal hyperalgesia 3 and 7 days following peripheral injection of formalin. Formalin induced a significant decrease of thermal and mechanical threshold in the injected and contralateral paw.

Salvinorin A reduces mechanical allodynia and spinal neuronal hyperexcitability induced by peripheral formalin injection.

Background: Salvinorin A (SA), the main active component of Salvia Divinorum, is a non-nitrogenous kappa opioid receptor (KOR) agonist. It has been shown to reduce acute pain and to exert potent antinflammatory effects. This study assesses the effects and the mode of action of SA on formalin-induced persistent pain in mice.

Role of metabotropic glutamate receptor 1 in the basolateral amygdala-driven prefrontal cortical deactivation in inflammatory pain in the rat.

Plastic changes in the amygdala and limbic cortex networks have been widely shown in chronic pain. We have here investigated the role of group I metabotropic glutamate receptors (mGluRs) in the basolateral amygdala (BLA) pre-infra-limbic (PL-IL) divisions of the medial prefrontal cortex (mPFC) neuron connections after carrageenan-induced inflammatory pain in the rat. Intra-plantar injection of carrageenan decreased either spontaneous or mechanically/electrically evoked activity of PL cortex pyramidal neurons which responded with excitation in a way prevented by CPCOOEt, a selective mGluR1 antagonist, though not by MPEP, a selective mGluR5 antagonist.

Thrombophilic gene mutations in children with migraine.

In 35 patients of both sexes (18 boys and 17 girls), mean age 8.9 ± 4.5 years, affected by migraine both with (45.

Changes in cannabinoid receptor subtype 1 activity and interaction with metabotropic glutamate subtype 5 receptors in the periaqueductal gray-rostral ventromedial medulla pathway in a rodent neuropathic pain model.

This study analyzed the effect of intra-ventrolateral periaqueductal grey (VL PAG) cannabinoid receptor (CB) stimulation on pain responses and rostral ventromedial medulla (RVM) neural activity in the chronic constriction injury (CCI) model of neuropathic pain in rats. Interaction between CB1 and metabotropic glutamate 1 and 5 (mGlu(1)/mGlu(5)) receptors was also investigated together with the expression of the CB1 receptor associated Gαi3 and cannabinoid receptor interacting 1a (CRIP 1a) proteins and the endocannabinoid synthesising and hydrolysing enzymes. In rats not subjected to CCI-induced pain, intra-VL PAG (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212-2) (2-4-8 nmol), a CB receptor agonist, increased the tail flick latency and changed the ongoing activity of RVM OFF and the tail flick-related activity of the ON and OFF cells, accordingly.

Effects of intra-ventrolateral periaqueductal grey palmitoylethanolamide on thermoceptive threshold and rostral ventromedial medulla cell activity.

Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α (PPAR-α) ligand, exerts antinociceptive and anti-inflammatory effects. PEA (3 and 6 nmol) was microinjected in the ventrolateral periaqueductal grey (VL PAG) of male rats and effects on nociceptive responses and ongoing and tail flick-related activities of rostral ventromedial medulla (RVM) ON and OFF cells were recorded. Intra-PAG microinjection of PEA reduced the ongoing activity of ON and OFF cells and produced an increase in the latency of the nociceptive reaction.

Transient receptor potential vanilloid type 1 and pain development.

Transient receptor potential vanilloid type 1 (TRPV1), a ligand-gated cation channel, is a polymodal nocitransducer widely expressed within pain transmitting/modulating areas of the peripheral and central nervous system. TRPV1 is both activated and sensitized by inflammatory endogenous mediators during inflammatory pain conditions and appears to be up regulated in neuropathic pain conditions. Owing to its role as pain integrator, its widespread expression in pain neuraxis and its involvement in pain development TRPV1 offers an exciting opportunity for therapeutic interventions in pain management.

EP1 receptor within the ventrolateral periaqueductal grey controls thermonociception and rostral ventromedial medulla cell activity in healthy and neuropathic rat.

The aim of this study was to investigate the expression of prostaglandin EP1 receptor within the ventrolateral periaqueductal grey (VL PAG). The role of VL PAG EP1 receptor in controlling thermonociception and rostral ventromedial medulla (RVM) activity in healthy and neuropathic rats was also examined. EP1 receptor was indeed found to be expressed within the VL PAG and co-localized with vesicular GABA transporter.

A progranulin mutation associated with cortico-basal syndrome in an Italian family expressing different phenotypes of fronto-temporal lobar degeneration.

Cortico-basal syndrome (CBS) is a rare neurodegenerative disease characterised by movement and cognitive disorders. It occurs along the spectrum of fronto-temporal lobar degeneration (FTLD), which also includes fronto-temporal dementia (FTD) and progressive supranuclear palsy (PSP). FTLD has recently been shown to be associated with mutations in GRN gene, coding for progranulin, a multifunctional secreted glycoprotein involved in cell cycle, inflammation and tissue repair.

Metabotropic glutamate receptor subtype 8 in the amygdala modulates thermal threshold, neurotransmitter release, and rostral ventromedial medulla cell activity in inflammatory pain.

The amygdala is a crucial area in controlling the threshold of pain and its emotional component. The present study has evaluated the effect of a metabotropic glutamate 8 receptor (mGluR8) stimulation in the central nucleus of the amygdala (CeA) on the thermoceptive threshold and on CeA serotonin (5-HT), glutamate (Glu), and GABA release in normal and carrageenan-induced inflammatory pain conditions in rats. Furthermore, the activity of rostral ventromedial medulla (RVM) putative "pronociceptive" ON and "antinociceptive" OFF cells has been evaluated.

Moving towards supraspinal TRPV1 receptors for chronic pain relief.

Transient receptor potential vanilloid type 1 (TRPV1) receptor is a non selective ligand-gated cation channel activated by capsaicin, heat, protons and endogenous lipids termed endovanilloids. As well as peripheral primary afferent neurons and dorsal root ganglia, TRPV1 receptor is also expressed in spinal and supraspinal structures such as those belonging to the endogenous antinociceptive descending pathway which is a circuitry of the supraspinal central nervous system whose task is to counteract pain. It includes periaqueductal grey (PAG) and rostral ventromedial medulla (RVM) whose activation leads to analgesia.

The Role of Cannabinoid Receptors in the Descending Modulation of Pain.

The endogenous antinociceptive descending pathway represents a circuitry of the supraspinal central nervous system whose task is to counteract pain. It includes the periaqueductal grey (PAG)-rostral ventromedial medulla (RVM)-dorsal horn (DH) axis, which is the best characterized pain modulation system through which pain is endogenously inhibited. Thus, an alternative rational strategy for silencing pain is the activation of this anatomical substrate.

Reliability of red blood cell indices and formulas to discriminate between beta thalassemia trait and iron deficiency in children.

Iron deficiency (ID) and beta thalassemia trait (betaTT) are the most common causes of hypochromia and microcytosis. This study evaluates the reliability of some of the red blood cell (RBC) indices and the formulas used in the differentiation between betaTT and ID in a cohort of 458 children aged between 1.8 and 7.

Intra-periaqueductal grey microinjections of an imidazo[1,2-b]pyridazine derivative, DM2, affects rostral ventromedial medulla cell activity and shows antinociceptive effect.

The 6-methoxy-2-phenylimidazo[1,2-b]pyridazine-3-carboxylic acid, DM2, exerts anti-absence activity and blocks Cav3.1 channel, a T-type voltage-dependent Ca(2+) channel subtype, in vitro. The current study investigated the effect of intra-ventrolateral periaqueductal grey (VLPAG) administration of DM2 on formalin-induced nocifensive responses in rats.

Effect of Helicobacter pylori eradication on platelet count in children with chronic idiopathic thrombocytopenic purpura.

Recent reports have suggested, particularly in adults, an association between Helicobacter pylori infection (HPI) and chronic idiopatic thrombocytopenic purpura (cITP) with improvement of platelet count after eradication therapy. We investigated the association of HPI and cITP and the effect of HP eradication therapy on thrombocytopenia in a population of 24 children of both sexes mean age 8.0+/-0.

Twelve-month azathioprine as maintenance therapy in early diffuse systemic sclerosis patients treated for 1-year with low dose cyclophosphamide pulse therapy.

Objective: To investigate the role of azathioprine in maintaining improvement after 1-year low-dose IV pulse CYC therapy in patients with early diffuse Systemic Sclerosis (dcSSc).

Methods: Thirteen patients with early dcSSc who had completed a year of treatment with low-dose IV pulse CYC underwent AZA treatment (100 mg/day) in a prospective 1-year study. Modified Rodnan skin score (mRss), Health Assessment Questionnaire-Disability Index (HAQ-DI), forced vital capacity (FVC), and diffusing lung capacity for CO (DLCO) were assessed as outcome measures.

Neuropathic pain and the endocannabinoid system in the dorsal raphe: pharmacological treatment and interactions with the serotonergic system.

We used a model of neuropathic pain consisting of rats with chronic constriction injury (CCI) of the sciatic nerve, in order to investigate whether endocannabinoid levels are altered in the dorsal raphe (DR) and to assess the effect of repeated treatment with (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate, a synthetic cannabinoid agonist, or N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404), an inhibitor of endocannabinoid reuptake, on DR serotonergic neuronal activity and on behavioural hyperalgesia. CCI resulted in significantly elevated anandamide but not 2-arachidonoylglycerol levels in the DR. Furthermore, as well as thermal and mechanical hyperalgesia, CCI caused serotonergic hyperactivity (as shown by the increase of basal activity of serotonergic neurones, extracellular serotonin levels and expression of 5-HT1A receptor gene).

Constitutive law describing the phenomenology of subyield mechanically stimulated glasses.

The principal features of the volumetric as well as the viscoelastic response of mechanically stimulated glasses can be summarized as follows: (i) the time-aging time shift factors contract upon increasing the probe stress (i.e., the stress apparently modifies the volume recovery kinetics), (ii) the volume recovery baseline remains unaltered (i.

Sleeping disorders in early chronic kidney disease.

Studies in patients on maintenance hemodialysis have disclosed a high prevalence of sleeping disorders, which have been linked to various factors including blood urea levels, creatinine levels, parathyroid hormone levels, anemia, systolic and diastolic blood pressure, quality of life, disease intrusiveness, and comorbidities. In contrast, few studies have been performed in patients with chronic kidney disease (CKD), who represent the target of the present study. A group of 52 CKD patients were enrolled after characterization of their renal function.

Role of periaqueductal grey prostaglandin receptors in formalin-induced hyperalgesia.

In this study we have investigated the role of periaqueductal grey prostaglandin receptors in formalin-induced hyperalgesia in mice. Glutamate and GABA release changes have been monitored by in vivo microdialysis. Intra-periaqueductal grey microinjections of misoprostol, a non-selective prostaglandin receptor agonist, increased nociceptive responses in the formalin test only during the late phase.

Spinal anaesthesia using hyperbaric 0.75% vs hyperbaric 1% bupivacaine: a double blind comparison.

Aim: The aim of this study was to compare the anesthetic effects, potency and postoperative outcome of 0.75% and 1% concentrations of hyperbaric bupivacaine in selective spinal anesthesia.

Methods: We enrolled 40 patients in a double blind fashion in 2 groups (A= 0.

Azathioprine and interferon beta(1a) in relapsing-remitting multiple sclerosis patients: increasing efficacy of combined treatment.

Current treatments of relapsing-remitting multiple sclerosis (RRMS) with immunosuppressive or immunomodulatory drugs have been shown to modify the course of the disease in a significative number of patients. However, in many cases, the response to either interferon beta (IFN-beta) or azathioprine (AZA) treatments was not satisfactory and new therapeutic approaches are needed. We studied clinical and MRI efficacy, safety and tolerance of AZA and IFN-beta(1a) combined therapy in 23 patients with clinically definite RRMS, who had not previously been responsive to either monotherapies.

Differences in constitutive and activation-induced expression of CD69 and CD95 between normal and chronic lymphocytic leukemia B cells.

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a sustained accumulation of long-lived and well-differentiated B lymphocytes in lymphoid tissues, peripheral blood and bone marrow. Although the pathogenesis of this disease is not entirely understood, altered apoptosis is believed to play a relevant role in B-CLL. In this study, we compared the expression of CD95, the best characterized surface molecule involved in triggering the apoptotic machinery, on normal and CLL B cells before and after in vitro activation with polyclonal stimulators.

The heart in uremia: role of hypertension, hypotension, and sleep apnea.

Cardiovascular disease is the leading cause of morbidity and mortality in end-stage renal disease. Causes include those usually found in the general population, those related to the uremic status, and those related to dialytic treatment. Hypertension, hypotension, anemia, hypoalbuminemia, malnutrition, dyslipidemia, reactive C protein, calcium-phosphate product, dialysis modalities, and hyperhomocysteinemia are discussed extensively.

Diagnosis and follow-up of cystinuria: use of proton magnetic resonance spectroscopy.

Proton Nuclear Magnetic Resonance (NMR) Spectroscopy of urine (as well as of other biological fluids) is a very powerful technique enabling multi-component analysis useful in both diagnosis and follow-up of a wide range of inherited metabolic diseases. Among these pathologies, cystinuria is characterised by accumulation in urine of four dibasic amino acids, namely lysine, arginine, ornithine and cystine; the last one, being only slightly water soluble, generates urolithiasis. The mentioned aminoacids can be detected in the urine NMR spectrum of cystinuric patients, the most abundant being the lysine (5 mM and over are often detected), whose typical signals become very high; arginine and ornithine are also usually detectable, although pathologic concentrations are lower (usually below 2mM).