Advances that further elucidate the mechanism(s) of action of gra

Advances that further elucidate the mechanism(s) of action of granins, coupled with improvements in biomarker technology and direct clinical application, should increase the translational

effectiveness of this family of proteins in disease diagnosis and drug discovery. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Orexins are neuropeptides produced in the lateral hypothalamus and implicated in regulation of sleep-wake cycle. Selective loss of orexin neurons is found in the brain of patients with narcolepsy, but the mechanisms of this pathological change are unclear. A previous study showed that excessive stimulation of N-methyl-D-aspartate (NMDA) receptors by quinolinic acid (QA) caused selective loss of orexin neurons in rat hypothalamic slice culture. Here we examined QA toxicity on orexin neurons and melanin-concentrating learn more hormone (MCH) neurons in vivo. Contrary to the expectation, injection of QA (60 and 120 nmol) into the lateral hypothalamus of male C57BL/6 mice caused selective loss of MCH neurons rather than orexin neurons, and this toxicity of QA was attenuated by MK-801, an NMDA receptor antagonist. Selective loss of MCH

neurons with preserved orexin neurons was observed even when GABA(A) receptor antagonists such as bicuculline and picrotoxin were injected with QA. A significant decrease in the number of orexin neurons was induced when QA injection was performed in the dark phase of diurnal cycle, but the degree of the decrease was still lower than that in the number of MCH neurons. Finally, OTX015 QA (60 nmol) induced selective loss of MCH neurons also in young rats at 3-4 weeks of age. These results do not support the hypothesis that acute excitotoxicity mediated by NMDA receptors is responsible for the pathogenesis of narcolepsy. (C) 2010 IBRO. Published GSK872 research buy by Elsevier Ltd. All rights reserved.”
“Pleiotrophin (PTN) is a neurotrophic factor with important effects in survival and differentiation of dopaminergic neurons that has been suggested to

play important roles in drug of abuse-induced neurotoxicity. To test this hypothesis, we have studied the effects of amphetamine (10 mg/kg, four times, every 2 h) on the nigrostriatal pathway of PTN genetically deficient (PTN-/-) mice. We found that amphetamine causes a significantly enhanced loss of dopaminergic terminals in the striatum of PTN-/- mice compared to wild type (WT+/+) mice. In addition, we found a significant decrease (similar to 20%) of tyrosine hydroxylase (TH)-positive neurons only in the substantia nigra of amphetamine-treated PTN-/- mice, whereas this area of WT+/+ animals remained unaffected after amphetamine treatment. This effect was accompanied by enhanced amphetamine-induced astrocytosis in the substantia nigra of PTN-/- mice.

Large-scale epidemiologic studies are necessary to further charac

Large-scale epidemiologic studies are necessary to further characterize this disease and to assess its potential long-term sequelae. This epidemic of environmental kidney disease highlights the morbidity associated with adulterated food products available in today’s global marketplace

and reminds us of the unique vulnerability of the kidney to environmental insults. Melamine is the latest in a growing list of diverse potentially toxic compounds about which nephrologists and other health-care providers responsible for the diagnosis and management of kidney disease must now be aware.”
“OBJECTIVE: The optimal management of seizures associated with cerebral cavernous malformations (CCMs) is unclear. The aim of this study was to determine the efficacy of surgery in the management of CCM associated siezures.

METHODS: We conducted a retrospective review Bucladesine mouse with follow-up of 164 patients who underwent microsurgical resection of supratentorial CCMs. Clinical andradiographic data were collected and then analyzed to determine predictors of developing epilepsy and predictors of postoperative seizure control after microsurgical

resection.

RESULTS: Of the patients, MX69 61.5% presented with seizures, and 34.7% had clinically defined epilepsy. The development of epilepsy was associated with CCMs located in the temporal lobe and the absence of symptomatic hemorrhage. After microsurgical resection in 44 patients with intractable

epilepsy, 72.7% were completely seizure-free (Engel class 1), 11.4% had rare seizures (Engel class 2), 4.5% had meaningful improvement (Engel class 3) and 11.4% had no improvement (Engel class 4). Predictors of complete seizure freedom were gross total resection, smaller CCMs, and the absence of secondary generalized seizure (94% of patients were seizure-free with all 3 predictors).

CONCLUSION: Surgery is a safe and effective treatment for seizures associated with CCMs.”
“Through screening, diagnosing, and treating childhood urinary stones induced see more by melamine-tainted formula, Chinese doctors obtained more experience with the clinical as well as the imaging features of the stones, although there still are many questions regarding melamine-associated stones. By reviewing the earlier reports on animals along with our recent experiences with humans, we concluded that there was no evidence either from animal experiments or from humans to support the direct toxicity of melamine on the kidney, although a feasible follow-up and assessment might be needed. It is also speculated that further studies on the mechanism of stone formation may need to take into account human internal metabolism changes and tubular function.”
“OBJECTIVE: The lateral supraorbital approach for safely and completely removing olfactory groove meningiomas was assessed.

However, the role of staff support may either facilitate or compl

However, the role of staff support may either facilitate or complicate emotional strain and merits additional study.”
“OBJECTIVE: Reported biochemical remission Selleck CX-6258 rates have ranged widely after stereotactic radiosurgery for patients with hormone-secreting pituitary adenomas. Confounding variables include histology, radiation dose, use of pituitary-suppressive medications, and length of follow-up.

METHODS: A retrospective review of 46 patients with pituitary adenomas (growth

hormone-secreting, n = 27; prolactin-secreting, n = 11; adrenocorticotropin-secreting, n = 8) undergoing radiosurgery between January 1990 and December 2003 was conducted. All received a tumor margin dose of 18 Gy or more and were off pituitarysuppressive medications for at least 1 month before radiosurgery. The groups were similar with regard to irradiated volume, radiation dose, and follow-up. The median endocrinological follow-up see more after radiosurgery was 54 months.

RESULTS: The 4-year remission rates were 87% for patients with Cushing’s disease, 67% for patients with acromegaly, and 18% for patients with

prolactinomas. Patients with oversecretion of adrenocorticotropin or growth hormone were more likely to achieve remission after radiosurgery than patients with prolactinomas (hazard ratio, 4.4; 95% confidence interval, 1.1-18.2; P = 0.04). Of 44 patients with normal

or partial anterior pituitary function before radiosurgery, 16 (36%) developed one or more new anterior pituitary deficits. The incidence of new anterior pituitary deficits was 26% at 4 years. No differences were noted in the incidence of new anterior deficits among the groups.

CONCLUSION: There seems to be a differential sensitivity after radiosurgery for hormone-secreting pituitary adenomas. Remission rates are greater for patients with Cushing’s disease and acromegaly, whereas radiosurgery is less effective in achieving biochemi-”
“Cisplatin is one of the most widely used and most potent Capmatinib price chemotherapy drugs. However, side effects in normal tissues and organs, notably nephrotoxicity in the kidneys, limit the use of cisplatin and related platinum-based therapeutics. Recent research has shed significant new lights on the mechanism of cisplatin nephrotoxicity, especially on the signaling pathways leading to tubular cell death and inflammation. Renoprotective approaches are being discovered, but the protective effects are mostly partial, suggesting the need for combinatorial strategies. Importantly, it is unclear whether these approaches would limit the anticancer effects of cisplatin in tumors.

The impairment of posterior cingulate and precuneus could be an i

The impairment of posterior cingulate and precuneus could be an important marker to distinguish aMCI from healthy aging in the resting-state. Moreover, the OTX015 chemical structure increased regional homogeneity changes would be consistent with compensation for damage to the medial temporal

regions and limbic structures, perhaps by recruitment of alternative regions. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Recent observations of F-actin dynamics call for theoretical models to interpret and understand the quantitative data. A number of existing models rely on simplifications and do not take into account F-actin fragmentation and annealing. We use Gillespie’s algorithm for stochastic simulations of the F-actin dynamics including fragmentation and annealing. The simulations vividly illustrate that fragmentation and annealing have little influence on the shape of the polymerization curve and on nucleotide profiles within filaments but drastically affect the F-actin length distribution, making it exponential. We find that recent surprising measurements of high length diffusivity at the critical concentration cannot be explained by fragmentation and annealing events unless both fragmentation rates and frequency of undetected

fragmentation and annealing events are greater than previously thought. The simulations compare well with experimentally measured actin polymerization data and Thiazovivin chemical structure lend additional support to a number of existing theoretical

models. (c) 2008 Elsevier Ltd. All rights reserved.”
“Oxidative stress is believed to contribute to neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. The present study was undertaken to evaluate the possible antioxidant neuroprotective effect of genistein against neuronal death in hippocampal CA1 neurons following transient global cerebral ischemia in the rat. Transient global cerebral ischemia was induced in male Sprague-Dawley rats by four-vessel-occlusion for 10 min. At various times of reperfusion, the histo pathological changes and the levels of www.selleck.cn/products/acy-738.html mitochondria-generated reactive oxygen species (ROS),malondialdehyde (MDA), cytosolic cytochrome c and caspase-3 activity in hippocampus were measured. We found extensive neuronal death in the CA1 region at day 5 after I/R. The ischemic changes were preceded by increases in ROS generation and MDA concentration and followed by increased cytosolic cytochrome c, and subsequently caspase-3 activation and apoptosis. Treatment with genistein (15 mg/kg, i.p.) significantly attenuated ischemia-induced neuronal death. Genistein administration also decreased ROS generation, MDA concentration and the apoptotic indices.

The use of the recently developed ScriptCap post-transcriptional

The use of the recently developed ScriptCap post-transcriptional enzymatic capping system, followed by optimized Neon mediated electroporation of the highly permissive

RAW 264.7 cells, resulted in the rapid and robust recovery of infectious MNV. Transfection of cells capable of supporting virus replication but not permissive to virus infection, namely human or hamster kidney cells, also resulted in robust recovery of infectious virus without subsequent amplification by multiple rounds of re-infection. This latter system may provide a reproducible method to measure the specific infectivity of mutant norovirus RNA allowing the accurate quantitation of the effect of mutations on norovirus replication. (c) 2010 Elsevier B.V. this website All rights reserved.”
“Miscanthus x giganteus, energycane, and Panicum virgatum (switchgrass) are three potential biomass crops being evaluated for commercial cellulosic ethanol production. Viral diseases are potentially significant threats to these crops. Therefore, identification of viruses infecting these bioenergy crops is important for quarantine purposes, virus resistance breeding, and production of virus-free planting materials.

The application is described of sequence-independent amplification, for the identification of RNA viruses in bioenergy crops. The method involves virus partial purification from a small amount of infected leaf tissue (miniprep), extraction of viral RNA, amplification of randomly primed cDNAs, cloning, sequencing, and BLAST

searches for sequence homology in the GenBank. This method Dinaciclib research buy has distinct advantage over other virus characterization techniques in that it does not require reagent specific to target viruses. Using this method, a possible new species was identified in the genus Marafivirus selleck compound in switchgrass related to Maize rayado fino virus, its closest relative currently in GenBank. Sugarcane mosaic virus (SCMV), genus Potyvirus, was identified in M. x giganteus, energycane, corn (Zea mays), and switchgrass. Other viruses identified were: Maize dwarf mosaic virus (MDMV), genus Potyvirus, in johnsongrass (Sorghum halepense); Soil borne wheat mosaic virus (SBWMV), genus Furovirus, in wheat (Triticum aestivum); and Bean pod mottle virus (BPMV), genus Comovirus, in soybean (Glycine max). The method was as sensitive as conventional RT-PCR. This is the first report of a Marafivirus infecting switchgrass, and SCMV infecting both energycane and M. x giganteus. (c) 2010 Elsevier B.V. All rights reserved.”
“The bipartite Abutilon mosaic virus (AbMV) was engineered as a versatile silencing vector in which the coat protein gene of DNA A was deleted and replaced by sequences of interest. Plants transgenic for the dimeric AbMV DNA B component were used as test hosts to minimize the risk of unintended release of the recombinant DNA. The vector construct was stable genetically upon systemic infection and, in common with the parental virus, the vector remained phloem-limited.

In 265 procedures (40%) computerized tomography was done between

In 265 procedures (40%) computerized tomography was done between 30 and 90 days postoperatively. They comprised the study group. Residual fragments were defined as any residual ipsilateral stone greater than 2 mm.

Results: Included in the study were 121 men and 127 women with a mean age of 47

years. Mean target stone diameter was 7.6 mm. The stone location was the kidney in 30% of cases, ureter in 50%, and kidney and ureter in 20%. Residual fragments were detected on computerized tomography after 101 of 265 procedures (38%). Pretreatment stone size was associated with residual fragments at a rate of 24%, 40% DMH1 cost and 58% for stones 5 or less, 6 to 10 and greater than 10 mm, respectively (p < 0.001). Additionally, stone location in the kidney (p < 0.001) or the kidney and ureter (p = 0.044), multiple calculi (p = 0.003), longer operative time (p = 0.008) and exclusive use of flexible ureteroscopy (p = 0.029) were associated with residual fragments. In a multivariate model only pretreatment stone diameter greater than 5 mm was independently associated

with residual fragments after ureteroscopy (diameter 6 to 10 and greater than 10 mm OR 2.03, p = 0.03 and OR 3.74, p = 0.003, respectively).

Conclusions: Of patients who underwent ureteroscopic lithotripsy for calculi 38% had residual fragments by computerized tomography criteria, including more than 50% with stones 1 cm or greater. Such data may guide expectations regarding the success of ureteroscopy in attaining stone-free status.”
“There is mounting evidence that, in addition to texture and olfaction, taste plays a role in the detection of long https://www.selleckchem.com/products/qnz-evp4593.html chain fatty acids. Triglycerides, the main components of oils and dietary fat, are hydrolyzed in the mouth by a lingual lipase secreted from the von Ebner gland and the released free fatty acids are detected by the taste system. GPR40 and GPR120, two fatty acid responsive G-protein-coupled receptors (GPCRs), are expressed in taste bud cells, and knockout mice lacking either of those receptors have blunted taste nerve responses to and reduced preference for fatty acids. Here we investigated whether

activation of those GPCRs is sufficient to elicit fat taste and preference. Five non-fatty acid agonists of GPR40 and two non-fatty acid agonists of GPR120 activated the glossopharyngeal nerve of wild-type mice but not of knockout mice lacking click here the cognate receptor. In human subjects, two-alternative forced choice (2-AFC) tests, triangle tests and sensory profiling showed that non fatty acid agonists of GPR40 dissolved in water are detected in sip and spit tests and elicit a taste similar to that of linoleic acid, whereas 2-AFC tests showed that two agonists of GPR120 in water are not perceived fattier than water alone. Wild-type mice did not show any preference for five agonists of GPR40, two agonists of GPR120 and mixtures of both agonists over water in two-bottle preference tests.

Eighteen SCA patients and 21 age-matched controls were tested Up

Eighteen SCA patients and 21 age-matched controls were tested. Upright standing was perturbed using rotations of the support surface. We recorded body motion and surface EMG. For lateral perturbations peaks in COM lateral velocity were larger in SCA patients than controls. These peaks were correlated with increased (“”hypermetric”") trunk roll downhill and reduced uphill knee flexion velocity. Subsequent arm abduction partially CB-5083 corrected the lateral instability. Early balance

correcting responses in knee and paraspinal muscles showed reduced amplitudes compared with normal responses. Later responses were consistent with compensation mechanisms for the lateral instability created by the stiffened knee and pelvis. We conclude that truncal hypermetria coupled with insufficient uphill knee flexion is the primary cause of lateral instability in SCA patients. Holding the knees and pelvis more rigid possibly permits a reduction in the controlled degrees of freedom and concentration on arm abduction to improve lateral instability. For backwards perturbations excessive posterior COM velocity

coincided with marked trunk hypermetric flexion forwards. We concluded that this flexion and the ensuing backwards shift of the pelvis result from rigidity which jeopardizes posterior stability. Timing considerations and the lack of confirmatory changes in amplitudes of EMG activity suggest that lateral and posterior instability in SCA is Selleck EPZ004777 primarily a biomechanical response to pelvis and knee rigidity resulting from Pitavastatin mw increased muscle background activity rather than changed evoked responses. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose: We investigated ethnic differences in the risk of post-pyelonephritic renal scarring in infants and children for possible genetic determinants.

Materials and Methods: We searched all peer reviewed articles published from 1980 through 2006 in the PubMed (R), MEDLINE (R) (Ovid), Cochrane Central Register of

Controlled Trials and EMBASE (R) databases for the keywords, “”renal scarring and pyelonephritis,”" “”renal fibrosis”" and “”kidney scarring.”" References were included only when they specified acute pyelonephritis defined by a fever, positive urine culture and areas of photopenia in the renal cortex on 99mtechnetium dimercapto-succinic acid renal scans, repeat dimercapto-succinic acid scans obtained at least 3 months after acute pyelonephritis to assess for renal cortical scar formation and absence of recurrent urinary tract infection during followup. When possible data were analyzed according to patients and renal units.

Results: Among 23 references the overall rates of renal scarring in terms of patients and renal units were 41.6% and 37.0%, respectively. In terms of patients the incidence of renal scarring following acute pyelonephritis varied by region, from 26.5% (Australia) to 49.0% (Asia).

2007) The prevalence of MetS in patients who took medication for

2007) The prevalence of MetS in patients who took medication for bipolar disorder (N = 152) was 270%. 25.0% and 25 7%, based on the definitions of the American Heart Association and the National Heart, Lung and Blood Institute’s adaptation of the Adult Treatment Panel III (AHA), the National Cholesterol Education Program for Adult Treatment Panel III (ATPIII) and the International Diabetes Federation (IDF), ICG-001 datasheet respectively The present study determined that the prevalence of MetS was significantly higher in patients with bipolar disorder than in the control

group, the odds ratios (OR) (95%CI) were 2.44 (1 35-4 40), 248 (1.34-459) and 257 (1.40-4.74), based on the definition of the ANA. ATPIII and IDF, respectively.The ISPR (95%CI) was 1.48(1 02-1 93), 1.54(1 05-2 03) and 1 98 (1 36-2 60). respectively Patients with medications for bipolar

disorder showed a significantly higher prevalence of increased waist circumference, elevated Inflammation related inhibitor triglycerides. and reduced HDL-cholesterol than the control group. The prevalence of MetS in patients taking medication for bipolar disorder was higher than that in the general population Obesity and dyslipidemia were particularly prevalent in patients with bipolar disorder (C) 2010 Elsevier Inc All rights reserved”
“This near infrared spectroscopy study investigated whether nonverbal human sounds representing different

basic emotions are able to specifically modulate temporo-parietal cortices, involved in auditory processing and attention. Forty-three adults (19 females and 24 males) were presented with sounds from the categories fear, disgust, and neutral. The stimuli were able to elicit the target emotions with sufficient specificity. The listening to fear-relevant sounds (e.g., screams of fear and pain) led to Urease increased activation of the right superior temporal gyrus and the bilateral supramarginal gyrus. The hemodynamic responses to disgusting sounds (e.g., sniffing, diarrhea) were smaller. Our findings point to a differential neuronal sensitivity of the human brain to two basic emotion elicitors in the auditory domain. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Objectives. In order to reveal the etiology and pathophysiology of trichotillomania (TTM). It is necessary to investigate which brain regions are involved in TTM, but limited knowledge exists regarding the neurobiology of TTM and the available functional neuroimaging studies of TTM are little The purpose of the present study was to investigate the specific brain regions involved in the pathophysiology of TTM with symptom provocation task using functional magnetic resonance imaging (fMRI) for children and adolescents with TTM

Methods.

p ) injection 15 min after L-dopa/benserazide ad ministration,

p.) injection 15 min after L-dopa/benserazide ad ministration,

as compared to a 60 min, 30 min or 0 min pretreatment. It was also found that i.p. administration of PG01037 could inhibit involuntary movements after they had achieved maximum intensity. PG01037 was found to attenuate AIM scores in these animals in a dose dependent manner with IC(50) value equal to a) 7.4 mg/kg following L-dopa/benserazide administration (8 mg/kg each, i.p.) and b) 18.4 mg/kg following the administration of apomorphine (0.05 mg/kg, s.c.). However, PG01037 did not effectively inhibit SKF 81297-dependent abnormal involuntary movements. Rotarod studies indicate that PGO1037 at Cyclopamine solubility dmso a dose of 10 mg/kg did not adversely affect motor ARS-1620 chemical structure coordination of the unilaterally lesioned rats. Evaluation of lesioned rats using a cylinder test behavioral paradigm indicated that PG01037 did not dramatically attenuate the beneficial effects Of L-dopa. These studies suggest that D3 dopamine receptor selective antagonists are potential pharmacotherapeutic candidates for the treatment of L-dopa-associated dyskinesia in patients with Parkinson’s Disease. (C) 2009 Published by Elsevier Ltd.”
“A panel of novel D2 and D3 dopamine receptor selective antagonists, partial agonists and full agonists have been evaluated for the ability to attenuate L-dopa-associated abnormal involuntary

movements (AIMs) in 6-hydroxydopamine (6-OHDA) unilaterally lesioned male Sprague Dawley rats, which is an animal model Of L-dopa-induced dyskinesia (LID). LID is often observed in patients with Parkinson’s Disease following chronic treatment with L-dopa. The intrinsic activity of these dopaminergic compounds was determined using a forskolin-dependent

adenylyl cyclase inhibition CA3 chemical structure assay with transfected HEK 293 cells expressing either the human D2Long or D3 dopamine receptor subtype. For the initial experiments the 5-HT1A receptor selective partial agonist buspirone was used to verify our ability to quantitate changes in total AIMs and AIMs minus locomotor scores. Two D2 dopamine receptor selective antagonists, SV 156 and SV 293, were evaluated and found to minimally attenuate AIM scores in these animals. Four members of our WC series of D3 dopamine receptor selective compounds of varying intrinsic activity at the D3 dopamine receptor subtype, WC 10, WC 21, WC 26 and WC 44, were also evaluated and found to attenuate AIM scores in a dose dependent manner. The in vivo efficacy of the compounds increased when they were administered simultaneously With L-dopa, as compared to when the compounds were administered 60 min prior to the L-dopa/benserazide. It was also found that the D3 receptor antagonist WC 10 could inhibit the involuntary movements after they had achieved maximum intensity.

These findings can be used to examine risk factors for the differ

These findings can be used to examine risk factors for the different trajectory groupings identified in the study.”
“Cytokines are soluble proteins secreted mainly by immune cells and

are key players in the induction and maintenance of pain. Pro-inflammatory cytokines are mostly algesic, while anti-inflammatory cytokines have analgesic properties. After the role of cytokines was shown in diverse animal models of pain, interest arose in the systemic and local regulation of cytokines in human pain states. Most clinical studies give evidence for an imbalance between pro- selleck screening library and anti-inflammatory cytokines in neuropathic and other pain states with pronounced pro-inflammatory cytokine profiles. Anti-cytokine treatment gives encouraging preliminary results and supports the notion of a crucial role of cytokines also in human pain states. Further research is needed for a better understanding of the mechanisms linking altered cytokine profiles to the sensation of pain. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Purpose: To our knowledge hypertension check details in children with ureteropelvic junction obstruction has not been reported in the literature as an indication for surgery. In addition, there has been no systematic research into the effect of relief of obstruction on existing hypertension. The aim of this study was to evaluate the proportion of children with ureteropelvic

junction obstruction with hypertension diagnosed preoperatively, and how hypertension developed after

relief of the obstruction.

Materials and Methods: We retrospectively reviewed patients operated on at our institution in the last 10 years for relief of ureteropelvic AZD6738 junction obstruction.

Results: Data were evaluated on 227 patients treated for ureteropelvic junction obstruction during the period 1996 to 2006. Preoperatively 11 of these patients had been diagnosed with hypertension. Hypertension alone was the major indication for surgery in 7 of these 11 patients. Postoperatively 10 patients became normotensive, while 1 is still receiving antihypertensive medication.

Conclusions: This study confirms that hypertension should be looked for in patients with dilated or obstructed upper urinary tracts, and considered an indication for surgery. In the vast majority of cases relief of obstruction cures hypertension.”
“This review explains symptoms and nature of neuropeptide signaling and its importance for clinical symptoms of CRPS. Neurogenic inflammation regularly accompanies excitation of primary afferent nociceptors. It has two major components-plasma extravasation and vasodilatation. The most important mediators are the calcitonin gene-related peptide (CGRP) and substance P (SP). After peripheral trauma immune reaction (e.g. cytokines) and the attempts of the tissue to regenerate (e.g. growth factors) sensitize nociceptors and amplify neurogenic inflammation.