Hemp cultivation opportunities for marginal lands development.

Agricultural diversification and high-quality products deriving from sustainable crops such as hemp can represent a solution to revitalize marginal areas and reverse land abandonment. This study aimed at comparing four different hemp cultivars (Carmagnola Selezionata, "CS"; Futura 75, "FUT"; Felina 32, "FEL"; Secuieni Jubileu, "JUB") to provide information to select the best suited cultivar for cultivation in mountain marginal areas and for specific end-use applications. Hemp cultivars were cultivated in a single experimental field to compare their ecological and agronomic behavior (duration of life cycle phases, plant size and biomass allocation, and plant resource-use strategies). Through metabolomic analysis of both vegetative and reproductive parts of the plants we tested the presence of substances of nutraceutical interest and traced seed nutritional profile. The four cultivars had different ecological and agronomic behavior, and nutritional profile. We found several compounds with potential pharmaceutical and nutraceutical values in all parts of the plant (leaves, inflorescences, and stems). JUB resulted the most suitable for seed production while CS showed the highest content of bioactive compounds in flowers and leaves. FUT, showed the best suitability for multi-purpose cultivation, while FEL seemed to be not appropriate for the cultivation in mountain area. The multi-disciplinary approach we adopted was effective in distinguish across hemp cultivars and provided information to farmers for the selection of the best hemp cultivar to select. Hemp had a high potential for cultivation in marginal lands, demonstrating to be an economic resource due to its multi-purpose use and to the possibility to generate high-added values products. Our results could serve as a stimulus for the reintroduction of this culture in the study area and in other similar environments.

Mechanisms and treatment of opioid-induced pruritus: Peripheral and central pathways.

BACKGROUND AND OBJECTIVE: Pruritus (also known as itch) is defined as an unpleasant and irritating sensation of the skin that provokes an urge to scratch or rub. It is well known that opioid administration can cause pruritus, which is paradoxical as itch and pain share overlapping sensory pathways. Because opioids inhibit pain but can cause itching. Significant progress has been made to improve our understanding of the fundamental neurobiology of itch; however, much remains unknown about the mechanisms of opioid-induced pruritus. The prevention and treatment of opioid-induced pruritus remains a challenge in the field of pain management. The objective of this narrative review is to present and discuss the current body of literature and summarize the current understanding of the mechanisms underlying opioid-induced pruritus, and its relationship to analgesia, and possible treatment options. RESULTS: The incidence of opioid-induced pruritus differs with different opioids and routes of administration, and the various mechanisms can be broadly divided into peripheral and central. Especially central mechanisms are intricate, even at the level of the spinal dorsal horn. There is evidence that opioid receptor antagonists and mixed agonist and antagonists, especially µ-opioid antagonists and κ-opioid agonists, are effective in relieving opioid-induced pruritus. Various treatments have been used for opioid-induced pruritus; however, most of them are controversial and have conflicting results. CONCLUSION: The use of a multimodal analgesic treatment regimen combined with a mixed antagonist and κ agonists, especially µ-opioid antagonists, and κ-opioid agonists, seems to be the current best treatment modality for the management of opioid-induced pruritus and pain. SIGNIFICANCE: Opioids remain the gold standard for the treatment of moderate to severe acute pain as well as cancer pain. It is well known that opioid-induced pruritus often does not respond to regular antipruritic treatment, thereby posing a challenge to clinicians in the field of pain management. We believe that our review makes a significant contribution to the literature, as studies on the mechanisms of opioid-induced pruritus and effective management strategies are crucial for the management of these patients.

Two Years of Active Pharmacovigilance Surveillance and Therapeutic Reconciliation in Frail Populations: The MEAP 3.0 Study.

Awareness related to the risk/benefit profile of therapies used in paediatric and elderly patients is limited. We carried out a study, called the MEAP 3.0 study, to collect and analyse evidence of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) that occurred in frail populations under polypharmacy in a real-world setting. Data were retrieved from reports of ADRs and pharmacological counselling from patients treated in hospitals and territorial health services. We collected 2977 ADRs reports and identified 'anti-infectives for systemic use' and 'cardiovascular system' as the most frequently implicated pharmacological classes in under-18 and over-65 patients, respectively. We detected 2179 DDIs, of which 10.7% were related to at least one ADR: 22 were classified as 'contraindicated' (7 in the paediatric group and 15 in the elderly one), and 61 as 'major' (6 in the paediatric patients and 55 in the geriatric ones), while 151 DDIs were classified as 'moderate' (10 referred to paediatric population, and 109 to elderly patient) and as 'minor' (1 in paediatric patients, and 31 in the elderly ones). The MEAP 3.0 project demonstrates that pharmacovigilance surveillance and therapeutic reconciliation are valid strategies to avoid potential DDIs and the occurrence of ADRs, allowing for personalised medicine.

Effects of oral morphine on experimentally evoked itch and pain: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Pain and itch share similar neuronal networks; hence, it is difficult to explain why opioids can relieve pain but provoke itching. The present human volunteer study aimed to investigate the similarities and differences in responses to experimentally provoked pain and itching to explore the underlying fundamental mechanisms. METHODS: Twenty-four healthy volunteers were enrolled in this single-center, randomized, double-blind, placebo-controlled, parallel-group trial. Three volar forearms and two mandibular areas were marked, and participants randomly received morphine (20 mg) or identical placebo tablets. Heat, cold, and pressure pain thresholds, and vasomotor responses were assessed at baseline and after oral morphine administration. Itch provocations were induced by intradermal application of 1 % histamine or a topical cowhage (non-histaminergic itch) to a marked area of the skin. The participants were subsequently asked to rate their itching and pain intensities. The assessments were repeated for all marked areas. RESULTS: Morphine caused analgesia, as assessed by the significant modulation of cold and pressure pain thresholds (p<0.05). There were no significant differences in histaminergic or non-histaminergic itch or pain intensity between the morphine and placebo groups. Superficial blood perfusion (vasomotor response) following histamine provocation was significantly increased by morphine (p<0.05) in both areas. No correlation was found between the provoked itch intensity and analgesic efficacy in any area or group. CONCLUSIONS: Oral administration of morphine caused analgesia without modulating itch intensities but increased neurogenic inflammation in response to histamine, suggesting that different opioid mechanisms in histaminergic and non-histaminergic neurons evoke neurogenic inflammation.

Administrative Databases and Diagnostic Therapeutic and Assistance Paths -PDTA- in the Monitoring Treatment of Rheumatoid Arthritis: The Experience of ATS Pavia.

Background: The current flows of the SSN represent the set of interest whose interconnection alone justifies the current study. These flows can be interconnected with other sources, institutional or otherwise, in order to answer well-defined questions. Objective: The objective of the study is to verify, through the analysis of administrative databases, any differences in the consumption of health resources between biological off-patent originator drugs and biosimilars in real clinical practice, with particular reference to the rheumatology area. Methods: Through the use of assisted databases (BDA) of ATS Pavia we evaluated the differences in terms of consumption of health resources related to the different drugs under analysis. Annual and daily costs were calculated by total patient cost, stratified for different treatments, considering the sum of total costs for the prescriptions of drugs subject to the analysis. Another objective was to evaluate the adherence of the drugs of interest, by utilizing specific indicators (MPR). Results: A total of 145 patients were analyzed. Among enrolled patients, 26.9% of users were treated with a biosimilar drug, while 73.1% with a biologic originator. Adherence is higher if it is considered the population treated with biosimilar drugs (82.1%). Total cost (including drug prescriptions, hospitalizations, outpatient services, tests for any cause) during the observation period of 1 year is 14,274.08. 87.7% of the total is attributable to drugs. Non-hospitalized patients are the least expensive, whether they were treated with biologics or biosimilars. Conclusion: In our sample, biosimilar drugs tend to be underused: the treatment of a patient with a chronic autoimmune disease is a clinical process that involves many health professionals, and a criticality could also derive from the difficult communication between the various professional figures who get involved with the whole patient treatment.

The temporal expression of circulating microRNAs after acute experimental pain in humans.

BACKGROUND: MicroRNAs (miRNAs) can modulate several biological systems, including the pain system. This study aimed to evaluate the temporal expression of circulating miRNAs in the plasma of healthy volunteers as a marker for epigenetic changes before and after an acute, experimental, pain provocation by intramuscular hypertonic saline injection. METHODS: Twenty volunteers were randomly allocated into two groups and received either hypertonic (pain) or isotonic (control) saline injection in the first dorsal interosseous muscle of their dominant hand. Pain intensity was continuously recorded for 20 minutes after injection on a VAS scale from 0 to 100 (0 indicates no pain and 100 the worst imaginable pain). Blood samples were taken at baseline, 30 minutes, 3 hours, and 24 hours post-injection, and plasma was separated. MiRNA extracts were used for RNA sequencing with the Illumina NextSeq platform. MiRNA transcripts were compared between the pain and the no-pain, control group at every time point. Significant differences were considered when folds were >2 and the False Discovery Rate was p < 0.05. RESULTS: After 30 minutes, 4 miRNAs were significantly altered in the pain group compared to controls, which increased to 24 after 3 hours and to 42 after 24 hours from baseline (p < 0.0001). Two miRNAs were consistently upregulated throughout the experiment. Enrichment analysis showed significant miRNAs involved in brain perception of pain, brain signalling and response to stimuli. CONCLUSIONS: This exploratory study is the first to report on the temporal expression of circulating miRNAs after an acute, human experimental muscle pain model. SIGNIFICANCE: This exploratory study evaluated the temporal profile of circulating miRNAs in the plasma of healthy subjects after acute experimental pain. Several miRNAs were altered in subjects at the times of follow-up after the acute pain model when compared to controls. MiRNAs previously associated with pain processes were altered in the pain group. Our results, by showing the fast and prolonged modifications of miRNA elicited by the acute experimental pain model, add new perspectives to the topic of epigenetics and pain.

Within-species variation of seed traits of dune engineering species across a European climatic gradient.

Within-species variation is a key component of biodiversity and linking it to climatic gradients may significantly improve our understanding of ecological processes. High variability can be expected in plant traits, but it is unclear to which extent it varies across populations under different climatic conditions. Here, we investigated seed trait variability and its environmental dependency across a latitudinal gradient of two widely distributed dune-engineering species (Thinopyrum junceum and Calamagrostis arenaria). Seed germination responses against temperature and seed mass were compared within and among six populations exposed to a gradient of temperature and precipitation regimes (Spiekeroog, DE; Bordeaux, FR; Valencia, ES; Cagliari, IT, Rome, IT; Venice, IT). Seed germination showed opposite trends in response to temperature experienced during emergence in both species: with some expectation, in populations exposed to severe winters, seed germination was warm-cued, whereas in populations from warm sites with dry summer, seed germination was cold-cued. In C. arenaria, variability in seed germination responses disappeared once the seed coat was incised. Seed mass from sites with low precipitation was smaller than that from sites with higher precipitation and was better explained by rainfall continentality than by aridity in summer. Within-population variability in seed germination accounted for 5 to 54%, while for seed mass it was lower than 40%. Seed trait variability can be considerable both within- and among-populations even at broad spatial scale. The variability may be hardly predictable since it only partially correlated with the analyzed climatic variables, and with expectation based on the climatic features of the seed site of origin. Considering seed traits variability in the analysis of ecological processes at both within- and among-population levels may help elucidate unclear patterns of species dynamics, thereby contributing to plan adequate measures to counteract biodiversity loss.

Evaluation of itch and pain induced by bovine adrenal medulla (BAM)8-22, a new human model of non-histaminergic itch.

Chronic itch is a socioeconomic burden with limited management options. Non-histaminergic itch, involved in problematic pathological itch conditions, is transmitted by a subgroup of polymodal C-fibres. Cowhage is traditionally used for studying experimentally induced non-histaminergic itch in humans but encounters some limitations. The present study, therefore, aims to design a new human, experimental model of non-histaminergic itch based on the application of bovine adrenal medulla (BAM)8-22, an endogenous peptide that activates the MrgprX1 receptor. Twenty-two healthy subjects were recruited. Different concentrations (0.5, 1 and 2 mg/ml) of BAM8-22 solution and vehicle, applied by a single skin prick test (SPT), were tested in the first session. In the second session, the BAM8-22 solution (1 mg/ml) was applied by different number of SPTs (1, 5 and 25) and by heat-inactivated cowhage spicules coated with BAM8-22. Provoked itch and pain intensities were monitored for 9 min, followed by the measurement of superficial blood perfusion (SBP) and mechanical and thermal sensitivities. BAM8-22 induced itch at the concentration of 1, 2 mg/ml (p < 0.05) and with the significantly highest intensity when applied through BAM8-22 spicules (p < 0.001). No concomitant pain sensation or increased SBP was observed. SBP increased only in the 25 SPTs area probably due to microtrauma from the multiple skin penetrations. Mechanical and thermal sensitivities were not affected by any of the applications. BAM8-22 applied through heat-inactivated spicules was the most efficient method to induce itch (without pain or changes in SBP and mechanical and thermal sensitivities) suggesting BAM8-22 as a novel non-histaminergic, human, experimental itch model.

Effects of Salicornia-Based Skin Cream Application on Healthy Humans' Experimental Model of Pain and Itching.

Halophyte plants are salt-tolerant and are acclimated for growth in saline soils such as along coastal areas. Among the halophytes, the Salicornia species have been used as both folk medicine and functional food for many years due to their high levels of bioactive compounds with supposed anti-inflammatory and antioxidative effects. However, the properties of Salicornia bioactive extracts on pain and itching still remain unclear. In this study, 30 healthy volunteers were randomized to treatments with 10% Salicornia-based cream or placebo cream for 24 or 48 h. On day 0, and 24 or 48 h post cream application, cold/heat detection and pain thresholds, mechanical pain thresholds and sensitivity, trans-epidermal water loss, histamine- and cowhage-evoked itch, and micro-vascular reactivity (neurogenic inflammation) were assessed to evaluate the analgesic, anti-pruritogenic and vasomotor effects. Skin permeability was reduced in the Salicornia-treated area for 48 h compared with 24 h application (p-value < 0.05). After 48 h of application, a decrease in mechanical-evoked itching (hyperkinesis) compared with 24 h treatment (p-value < 0.05) and increased warm detection and heat pain thresholds (p-value < 0.05) was found. Histamine-induced neurogenic inflammation showed a significant reduction in the cream-treated areas after 48 h compared with 24 h (p-value < 0.05). The results of this study indicate the overall inhibitory effect of Salicornia on hyperkinesis (mechanically evoked itch), the analgesic effect on thermal sensation, and modulation of the skin barrier architecture. Further studies are needed for the assessment of the long-term effects.

Sensory defunctionalization induced by 8% topical capsaicin treatment in a model of ultraviolet-B-induced cutaneous hyperalgesia.

Subpopulations of primary nociceptors (C- and Aδ-fibers), express the TRPV1 receptor for heat and capsaicin. During cutaneous inflammation, these afferents may become sensitized, leading to primary hyperalgesia. It is known that TRPV1+ nociceptors are involved in heat hyperalgesia; however, their involvement in mechanical hyperalgesia is unclear. This study explored the contribution of capsaicin-sensitive nociceptors in the development of mechanical and heat hyperalgesia in humans following ultraviolet-B (UVB) irradiation. Skin areas in 18 healthy volunteers were randomized to treatment with 8% capsaicin/vehicle patches for 24 h. After patches removal, one capsaicin-treated area and one vehicle area were irradiated with 2xMED (minimal erythema dose) of UVB. 1, 3 and 7 days post-UVB exposure, tests were performed to evaluate the development of UVB-induced cutaneous hyperalgesia: thermal detection and pain thresholds, pain sensitivity to supra-threshold heat stimuli, mechanical pain threshold and sensitivity, touch pleasantness, trans-epidermal water loss (TEWL), inflammatory response, pigmentation and micro-vascular reactivity. Capsaicin pre-treatment, in the UVB-irradiated area (Capsaicin + UVB area), increased heat pain thresholds (P < 0.05), and decreased supra-threshold heat pain sensitivity (P < 0.05) 1, 3 and 7 days post-UVB irradiation, while mechanical hyperalgesia resulted unchanged (P > 0.2). No effects of capsaicin were reported on touch pleasantness (P = 1), TEWL (P = 0.31), inflammatory response and pigmentation (P > 0.3) or micro-vascular reactivity (P > 0.8) in response to the UVB irradiation. 8% capsaicin ablation predominantly defunctionalizes TRPV1+-expressing cutaneous nociceptors responsible for heat pain transduction, suggesting that sensitization of these fibers is required for development of heat hyperalgesia following cutaneous UVB-induced inflammation but they are likely only partially necessary for the establishment of robust primary mechanical hyperalgesia.

Effect of Topical Analgesia on Desensitization Following 8% Topical Capsaicin Application.

To prevent pain associated with 8% capsaicin application, pretreatment with local anesthetics, such as EMLA (eutectic mixture of lidocaine 2.5% and prilocaine 2.5%), is considered an option. However, there is contradicting evidence regarding the effects of local analgesia on capsaicin-induced desensitization. In session 1, 2 skin areas in each forearm of 24 healthy volunteers were randomized to 2-hour pretreatment with EMLA/placebo cream. After pretreatment, 8% capsaicin patches were applied for 3 hours in 1 placebo and 1 EMLA pretreated area, obtaining the following four areas: Capsaicin + EMLA, Capsaicin + Placebo, EMLA alone, and Placebo. Pain intensity scores were assessed during the 3-hour application of capsaicin. Warmth detection, heat pain sensitivity, and microvascular reactivity were measured after the removal of capsaicin. After 24 hours, in session 2, all tests were repeated followed by histamine application in each area to examine itch intensity and neurogenic flare. Overall, EMLA caused significant reductions in capsaicin-induced pain compared with placebo (P= .007) and enhanced the capsaicin-induced increase in superficial blood perfusion immediately after the 3-hour capsaicin application (P< .01). Regardless of pretreatment, capsaicin induced heat hyperalgesia immediately after the application (P< .001). Twenty-four hours post application, heat pain sensitivity was normalized. However, WDT increased significantly (P< .001). Capsaicin tended to reduce the itch intensity and significantly reduced the neurogenic flare (P< .05) induced by histamine compared with EMLA alone. The findings suggest that pretreatment with topical analgesic cream reduces application site pain without interfering with the 8% topical capsaicin-induced desensitization. PERSPECTIVE: Pretreatment with local anesthetic EMLA cream might be considered a good therapeutic option to reduce the pain associated with 8% capsaicin application currently used for treatment of neuropathic pain syndromes. This study also suggests the existence of a synergistic effect of capsaicin and EMLA on the process of neurogenic inflammation.

Functional seed traits and germination patterns predict species coexistence in Northeast Mediterranean foredune communities.

BACKGROUND AND AIMS: The structure of plant communities, which is based on species abundance ratios, is closely linked to ecosystem functionality. Seed germination niche plays a major role in shaping plant communities, although it has often been neglected when explaining species coexistence. The aim of this work is to link the seed germination niche to community ecology, investigating how functional seed traits contribute to species coexistence. METHODS: Species selection was based on a database of 504 vegetation surveys from the Veneto coast (Italy). Through cluster analysis we identified the foredune community and selected all of its 19 plant species. By using the 'Phi coefficient' and frequency values, species were pooled in different categories (foundation species, accidental species of the semi-fixed dune and aliens), then the 19 species were grouped according to their germination responses to temperature and photoperiod through cluster analyses. For each germination cluster, we investigated germination trends against temperature and photoperiod by using generalized linear mixed models. KEY RESULTS: We identified four germination strategies: (1) high germination under all tested conditions ('high-germinating'); (2) high germination at warm temperatures in the dark ('dark warm-cued'); (3) high germination at warm temperatures in the light ('light warm-cued'); and (4) low germination, regardless of conditions ('low-germinating'). Foredune foundation species showed a narrow germination niche, being 'low-germinating' or 'dark warm-cued'. Annual species of semi-fixed dunes were 'high-germinating', while alien species were the only members of the 'light warm-cued' cluster. CONCLUSIONS: Our research suggests that different categories of species have dissimilar seed germination niches, which contributes to explaining their coexistence. Climatic events, such as rising temperature, could alter germination patterns, favouring seed regeneration of certain categories (i.e. alien and semi-fixed dune species) at the expense of others (i.e. foundation species, pivotal to ecosystem functioning), and hence potentially altering the plant community structure.

The time course of brief and prolonged topical 8% capsaicin-induced desensitization in healthy volunteers evaluated by quantitative sensory testing and vasomotor imaging.

Topically applied high-concentration capsaicin induces reversible dermo-epidermal denervation and depletion of capsaicin-sensitive nociceptors. This causes desensitization of distinct sensory modalities and is used to treat peripheral neuropathic pain and itch. For high-concentration capsaicin, the selectivity of loss of function and functional recovery rates of various afferent fibers subpopulations are unknown. This study used comprehensive quantitative sensory testing and vasomotor imaging to assess effectiveness, duration and sensory selectivity of high-concentration 8% capsaicin-ablation. Skin areas in 14 healthy volunteers were randomized to treatment with 8% capsaicin/vehicle patches for 1 and 24 h and underwent comprehensive sensory and vasomotor testing at 1, 7 and 21 days postpatch removal. Tests consisted of thermal detection and pain thresholds, tactile and vibration detection thresholds, mechanical pain threshold and mechanical pain sensitivity as well as micro-vascular and itch reactivity to histamine provocations. The 24 h capsaicin drastically inhibited warmth detection (P < 0.001), heat pain (P < 0.001) as well as histamine-induced itch (P < 0.05) and neurogenic flare (P < 0.001), but had no impact on tactile sensitivity, cold detection and cold pain. A marginal decrease in mechanical pain sensitivity was observed (P < 0.05). Capsaicin for 1 h had limited and transient sensory effects only affecting warmth and heat sensations. Time-dependent functional recovery was almost complete 21 days after the 24 h capsaicin exposure, while recovery of neurogenic inflammatory responsiveness remained partial. The psychophysically assessed sensory deficiencies induced by the used 8% capsaicin-ablation correspond well with a predominant effect on TRPV1+-cutaneous fibers. The method is easy to apply, well tolerated, and utilizable for studies on, e.g., interactions between skin barrier, inflammation and capsaicin-sensitive afferents.

UVB- and NGF-induced cutaneous sensitization in humans selectively augments cowhage- and histamine-induced pain and evokes mechanical hyperknesis.

Exaggerated itch responses to pruritic chemical provocations and mechanical stimuli are evident in patients with chronic itch, for example, in atopic dermatitis. Currently used human models of itch do not account for such itch sensitization features, and the mechanisms underlying clinical itch sensitization are unknown. This study utilized two established human models of cutaneous nociceptive sensitization to explore how pre-established inflammatory hyperalgesia (ultraviolet-B-irradiation; "UVB") and non-inflammatory neurotrophic pain sensitization (nerve growth factor; "NGF") alter sensitivity to chemical and mechanically evoked itch. Twenty healthy volunteers participated in the UVB experiment. Six volar forearm areas (2 cm diameter) were UVB irradiated with ≤2 × minimal erythemal dose, and two non-irradiated areas were used as controls. Sixteen healthy volunteers participated in the NGF experiment and had 2 µg intradermally injected (4 × 50 µL in 2 cm diameter areas) into both volar forearms. Isotonic saline was applied as control. Pain sensitivity measurements (mechanical and heat pain thresholds) were conducted to validate the models. Subsequently, itch was evoked using histamine and cowhage spicules in the sensitized skin areas, and itch/pain was rated using visual analogue scales. Mechanical hyperknesis (increased itch to punctuate stimuli) was probed with von Frey filaments before/after each itch provocation. Both UVB- and NGF models induced robust primary mechanical hyperalgesia (P < .01) and hyperknesis (P < .05). Neither of the models augmented itch in response to chemical itch provocations but significant increases specifically for pain ratings were observed for both histamine and cowhage (P < .05). This suggests that these models are of limited value as proxies for itch sensitization to pruritogens observed, e.g., in inflammatory dermatoses.

Dose-response study of topical allyl isothiocyanate (mustard oil) as a human surrogate model of pain, hyperalgesia, and neurogenic inflammation.

Despite being a ubiquitous animal pain model, the natural TRPA1-agonist allyl isothiocyanate (AITC, also known as "mustard oil") has only been sparsely investigated as a potential human surrogate model of pain, sensitization, and neurogenic inflammation. Its dose-response as an algogenic, sensitizing irritant remains to be elucidated in human skin. Three concentrations of AITC (10%, 50%, and 90%) and vehicle (paraffin) were applied for 5 minutes to 3 × 3 cm areas on the volar forearms in 14 healthy volunteers, and evoked pain intensity (visual analog scale 0-100 mm) and pain quality were assessed. In addition, a comprehensive battery of quantitative sensory tests was conducted, including assessment of mechanical and thermal sensitivity. Neurogenic inflammation was quantified using full-field laser perfusion imaging. Erythema and hyperpigmentation were assessed before, immediately after, and ≈64 hours after AITC exposure. AITC induced significant dose-dependent, moderate-to-severe spontaneous burning pain, mechanical and heat hyperalgesia, and dynamic mechanical allodynia (P < 0.05). No significant differences in induced pain hypersensitivity were observed between the 50% and 90% AITC concentrations. Acute and prolonged inflammation was evoked by all concentrations, and assessments by full-field laser perfusion imaging demonstrated a significant dose-dependent increase with a ceiling effect from 50% to 90%. Topical AITC application produces pain and somatosensory sensitization in a dose-dependent manner with optimal concentrations recommended to be >10% and ≤50%. The model is translatable to humans and could be useful in pharmacological proof-of-concept studies of TRPA1-antagonists, analgesics, and anti-inflammatory compounds or for exploratory clinical purposes, eg, loss- or gain-of-function in peripheral neuropathies.

Topography of itch: evidence of distinct coding for pruriception in the trigeminal nerve.

INTRODUCTION: Little is known about the topographical distribution of pruriception (in particular for nonhistaminergic itch), although conditions with chronic itch frequently occur in distinct anatomic and often bilateral patterns. This study aimed to investigate regional differences in the sensitivity to itch stimuli by assessing the intensity of itch, pain, and cutaneous neurogenic flare evoked by histamine and cowhage in different anatomic regions in 20 healthy volunteers. METHODS: Itch was induced by 1% histamine applied with a prick lancet or by insertion of 25±5 cowhage spicules in 4 regions: volar/dorsal forearm, lower back, and chin. The duration and intensity of itch and pain following each pruritic stimulus were measured by a continuous visual analogue scale (VAS0-100). Sensitivity to touch-evoked itch was assessed by von Frey filaments and cutaneous flare was quantified by full-field laser perfusion imaging. RESULTS: Peak itch intensity was lower at the chin (19.4±3.6) compared with other areas (mean of 3 locations; 41.3±4.4), independently of whether histamine or cowhage was applied (P<0.01). Baseline sensitivity to touch-evoked itch was higher on the chin (P<0.01), but here hyperknesis did not develop in contrast to other areas (P<0.05). Cutaneous flare was more intense but had a smaller dispersion at the chin, compared with other areas (P<0.01). DISCUSSION: In conclusion, sensitivity to histaminergic and non-histaminergic itch diverges considerably between body regions. Lower density of pruriceptive CMH and CMI-neurons or distinct neuronal substrates for itch in the mandibular part of the trigeminal area may explain the observed reduced itch and vasomotor responses.

The use of plant community attributes to detect habitat quality in coastal environments.

The monitoring of biodiversity has mainly focused on the species level. However, researchers and land managers are making increasing use of complementary assessment tools that address higher levels of biological organization, i.e. communities, habitats and ecosystems. Recently, a variety of frameworks have been proposed for assessing the conservation status of communities or ecosystems. Among the various criteria proposed, all the protocols suggest considering (i) spatial aspects (range and area), and (ii) qualitative aspects of specific structures and functions. However, changes to ecological function are difficult to quantify and many protocols end up by using qualitative criteria. The aim of this work was to test the efficacy of some plant community attributes for the detection of vegetation quality in sand dune plant communities. We chose plant community attributes that either help to distinguish a habitat from others (diagnostic components) or play a significant role in habitat function and persistence over time. We used a diachronic approach by contrasting up-to-date vegetation data with data from previous studies carried out within the same areas. Changes in species composition were detected through detrended correspondence analyses (detrended correspondence analyses), Multi-Response Permutation Procedures and Indicator Species Analysis, while structural changes were analyzed by comparing species richness, total species cover, ecological groups of species and growth forms through null models. Ecological groups such as native focal species and aliens, and growth forms proved their efficacy in discriminating between habitat types and in describing their changes over time. The approach used in this study may provide an instrument for the assessment of plant community quality that can be applied to other coastal ecosystems.

The Effect of Combined Skin and Deep Tissue Inflammatory Pain Models.

OBJECTIVE: Cutaneous hyperalgesia is prominent in the ultraviolet-B (UVB) model of inflammatory pain. This study investigated possible interactions between cutaneous and deep tissues hyperalgesia. METHODS: A total of 16 healthy volunteers participated in the study. Skin inflammation was induced unilaterally by UVB irradiation (three times of the individual minimal erythema dose) in square-shaped areas on the upper-trapezius and lower-back. Moderate delayed onset muscle soreness (DOMS) was induced bilaterally in the low-back by eccentric exercise. Cutaneous blood flow, mechanical thresholds, pressure pain thresholds (PPTs), temporal summation to repetitive pressure stimulation, and stimulus-response functions (SR curve) relating graded pressure stimulations and pain intensity were measured within and outside the irradiated areas, before and 24 hours after irradiation and eccentric muscle exercise. RESULTS: Compared with baseline (P < 0.05): the assessments 24 hours after irradiation demonstrated: 1) increased superficial blood flow inside and outside the irradiated areas and in the DOMS site; 2) reduced mechanical thresholds within the irradiated areas; 3) left-shifted SR curve function within and outside the irradiated areas; and 4) facilitated temporal summation of pain inside the irradiated areas and in the DOMS site. There was no significant influence of muscle hyperalgesia on skin measures in normal or UVB-inflamed skin. CONCLUSIONS: Moderate degrees of muscle sensitization could not facilitate UVB-induced cutaneous mechanical sensitivity, whereas UVB-induced neurogenic inflammation is enhanced when the DOMS is present.