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Decrease of olfactory function in Parkinson's disease (PD) is a well-investigated fact. Studies indicate that pharmacological treatment of PD fails to restore olfactory function in PD patients. The aim of this investigation was whether patients with PD would benefit from \"training\" with odors in terms of an improvement of their general olfactory function. It has been hypothesized that olfactory training should produce both an improved sensitivity towards the odors used in the training process and an overall increase of olfactory function. We recruited 70 subjects with PD and olfactory loss into this single-center, prospective, controlled non-blinded study. Thirty-five patients were assigned to the olfactory training group and 35 subjects to the control group (no training). Olfactory training was performed over a period of 12 weeks while patients exposed themselves twice daily to four odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and eugenol: cloves). Olfactory testing was performed before and after training using the \"Sniffin' Sticks\" (thresholds for phenyl ethyl alcohol, tests for odor discrimination, and odor identification) in addition to threshold tests for the odors used in the training process. Compared to baseline, trained PD patients experienced a significant increase in their olfactory function, which was observed for the Sniffin' Sticks test score and for thresholds for the odors used in the training process. Olfactory function was unchanged in PD patients who did not perform olfactory training. The present results indicate that olfactory training may increase olfactory sensitivity in PD patients.

A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. Sixty-four patients with painful chronic pancreatitis received pregabalin (150-300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy. The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9-1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5-2.0)) (P = 0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P = 0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy. The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient's individual sensory profile and thus comprises a significant step towards personalized pain medicine.

The use of quantitative sensory testing (QST) has become more widespread, with increasing focus on describing somatosensory profiles and pain mechanisms. However, the reliability of thermal QST has yet to be established. We systematically searched the literature using key medical databases. Independent reviewers evaluated reliability data using the Quality Appraisal for Reliability Studies checklist. Of the 21 studies we included in this review, we deemed 5 to have high methodological quality. Narrative analysis revealed that estimates of reliability varied considerably, but overall, the reliability of cold and warm detection thresholds ranged from poor to excellent, while heat and cold pain thresholds ranged from fair to excellent. The methodological quality of research investigating the reliability of thermal QST warrants improvement, particularly in terms of appropriate blinding. The results from this review showed considerable variability in the reliability of each thermal QST parameter.

Declines in sensory functioning with aging are evident for many of the senses. In the present study, thresholds were determined for somatosensory (warming and cooling temperature, pain, touch, and two-point discrimination) and taste stimuli in 178 healthy individuals aged 20-89 yrs. Somatosensory stimuli were applied to the upper lip (glabrous skin) and the chin (hairy skin). The sample was divided into two groups, based on a bimodal split “< 45 yrs” and “≥ 65 yrs”. In all instances, there were elevations in thresholds for the older individuals. Further, males were less sensitive than females for cool at the chin site, for touch, and for sour taste. We conclude that there are elevations in sensory thresholds with age for multimodal somatosensory and gustatory senses.

BackgroundMast cell activation is thought to be involved in visceral hypersensitivity, one of the main characteristics of the irritable bowel syndrome (IBS). A study was therefore undertaken to investigate the effect of the mast cell stabiliser ketotifen on rectal sensitivity and symptoms in patients with IBS.Methods60 patients with IBS underwent a barostat study to assess rectal sensitivity before and after 8 weeks of treatment. After the initial barostat, patients were randomised to receive ketotifen or placebo. IBS symptoms and health-related quality of life were scored. In addition, mast cells were quantified and spontaneous release of tryptase and histamine was determined in rectal biopsies and compared with biopsies from 22 age- and gender-matched healthy volunteers.ResultsKetotifen but not placebo increased the threshold for discomfort in patients with IBS with visceral hypersensitivity. This effect was not observed in normosensitive patients with IBS. Ketotifen significantly decreased abdominal pain and other IBS symptoms and improved quality of life. The number of mast cells in rectal biopsies and spontaneous release of tryptase were lower in patients with IBS than in healthy volunteers. Spontaneous release of histamine was mostly undetectable but was slightly increased in patients with IBS compared with healthy volunteers. Histamine and tryptase release were not altered by ketotifen.ConclusionsThis study shows that ketotifen increases the threshold for discomfort in patients with IBS with visceral hypersensitivity, reduces IBS symptoms and improves health-related quality of life. Whether this effect is secondary to the mast cell stabilising properties of ketotifen or H1 receptor antagonism remains to be further investigated.Trial Registration NumberNTR39, ISRCTN22504486.

RationaleMinocycline, a tetracycline antibiotic, inhibits activation of microglia. In preclinical studies, minocycline prevented development of opioid tolerance and opioid-induced hyperalgesia (OIH). The goal of this study was to determine if minocycline changes pain threshold and tolerance in individuals with opioid use disorder who are maintained on agonist treatment.MethodsIn this double-blind, randomized human laboratory study, 20 participants were randomized to either minocycline (200 mg/day) or placebo treatment for 15 days. The study had three test sessions (days 1, 8, and 15 of treatment) and one follow-up visit 1 week after the end of treatment. In each test session, participants were assessed on several subjective and cognitive measures, followed by assessment of pain sensitivity using the Cold Pressor Test (CPT). Daily surveys and cognitive measures using Ecological Momentary Assessment (EMA) were also collected four times a day on days 8 through 14 of treatment, and proinflammatory serum cytokines were assessed before and on the last day of treatment.ResultsMinocycline treatment did not change pain threshold or tolerance on the CPT. Similarly, minocycline did not change severity of pain, opioid craving, withdrawal, or serum cytokines. Minocycline treatment increased accuracy on a Go/No-Go task.ConclusionsWhile these findings do not support minocycline’s effects on OIH, minocycline may have a potential use as a cognitive enhancer for individuals with opioid use disorder, a finding that warrants further systematic studies.

Mangrove forests are highly productive tidal saline wetland ecosystems found along sheltered tropical and subtropical coasts. Ecologists have long assumed that climatic drivers (i.e., temperature and rainfall regimes) govern the global distribution, structure, and function of mangrove forests. However, data constraints have hindered the quantification of direct climate—mangrove linkages in many parts of the world. Recently, the quality and availability of global-scale climate and mangrove data have been improving. Here, we used these data to better understand the influence of air temperature and rainfall regimes upon the distribution, abundance, and species richness of mangrove forests. Although our analyses identify global-scale relationships and thresholds, we show that the influence of climatic drivers is best characterized via regional range-limit-specific analyses. We quantified climatic controls across targeted gradients in temperature and/or rainfall within 14 mangrove distributional range limits. Climatic thresholds for mangrove presence, abundance, and species richness differed among the 14 studied range limits. We identified minimum temperature-based thresholds for range limits in eastern North America, eastern Australia, New Zealand, eastern Asia, eastern South America, and southeast Africa. We identified rainfall-based thresholds for range limits in western North America, western Gulf of Mexico, western South America, western Australia, Middle East, northwest Africa, east central Africa, and west-central Africa. Our results show that in certain range limits (e.g., eastern North America, western Gulf of Mexico, eastern Asia), winter air temperature extremes play an especially important role. We conclude that rainfall and temperature regimes are both important in western North America, western Gulf of Mexico, and western Australia. With climate change, alterations in temperature and rainfall regimes will affect the global distribution, abundance, and diversity of mangrove forests. In general, warmer winter temperatures are expected to allow mangroves to expand poleward at the expense of salt marshes. However, dispersal and habitat availability constraints may hinder expansion near certain range limits. Along arid and semiarid coasts, decreases or increases in rainfall are expected to lead to mangrove contraction or expansion, respectively. Collectively, our analyses quantify climate–mangrove linkages and improve our understanding of the expected global- and regional-scale effects of climate change upon mangrove forests.

The presence of two spectrally different kinds of rod photoreceptors in amphibians has been hypothesized to enable purely rod-based colour vision at very low light levels. The hypothesis has never been properly tested, so we performed three behavioural experiments at different light intensities with toads (Bufo) and frogs (Rana) to determine the thresholds for colour discrimination. The thresholds of toads were different in mate choice and prey-catching tasks, suggesting that the differential sensitivities of different spectral cone types as well as task-specific factors set limits for the use of colour in these behavioural contexts. In neither task was there any indication of rod-based colour discrimination. By contrast, frogs performing phototactic jumping were able to distinguish blue from green light down to the absolute visual threshold, where vision relies only on rod signals. The remarkable sensitivity of this mechanism comparing signals from the two spectrally different rod types approaches theoretical limits set by photon fluctuations and intrinsic noise. Together, the results indicate that different pathways are involved in processing colour cues depending on the ecological relevance of this information for each task. This article is part of the themed issue ‘Vision in dim light’.

Regional empirical-statistical thresholds indicating the precipitation conditions initiating landslides are of crucial importance for landslide early warning system development. The objectives of this research were to use landslide and precipitation data in an empirical-statistical approach to (1) identify precipitation-related variables with the highest explanatory power for landslide occurrence and (2) define both trigger and trigger-cause based thresholds for landslides in Rwanda, Central-East Africa. Receiver operating characteristics (ROC) and area under the curve (AUC) metrics were used to test the suitability of a suite of precipitation-related explanatory variables. A Bayesian probabilistic approach, maximum true skill statistics and the minimum radial distance were used to determine the most informative threshold levels above which landslide are high likely to occur. The results indicated that the event precipitation volumes E, cumulative 1-day rainfall (RD1) that coincide with the day of landslide occurrence and 10-day antecedent precipitation are variables with the highest discriminatory power to distinguish landslide from no landslide conditions. The highest landslide prediction capability in terms of true positive alarms was obtained from single rainfall variables based on trigger-based thresholds. However, that predictive capability was constrained by the high rate of false positive alarms and thus the elevated probability to neglect the contribution of additional causal factors that lead to the occurrence of landslides and which can partly be accounted for by the antecedent precipitation indices. Further combination of different variables into trigger-cause pairs and the use of suitable thresholds in bilinear format improved the prediction capacity of the real trigger-based thresholds.