Multisensory interaction: different pain perception through smell and taste

Pain is a fundamental perception for our survival, acting as an alarm sys-tem. Nevertheless, patients may complain about the presence of pain even without actual physical harm. When neuropathic pain becomes chronic, those patients’ quality of life decreases dramatically, and more or less severe conse-quences on several life aspects become evident. Nowadays, alternative pain-relief therapies are increasingly necessary in order to avoid drugs shortcom-ings, as well as to reduce the costs for healthcare systems. Pain can be influenced by many factors, and the combined use of other senses in a multisensory interaction represents one of the most effective strategies to alter its perception. Smell and taste are strongly linked to emo-tion and cognition, and they might be useful in pain modulation, providing al-ternative approaches for pain treatment and management. Here, we provide evidence of the useful tools that smell and taste could represent when interacting with pain. Firstly, we report the results of a litera-ture review on adults stating the effects of olfactory and gustatory substances on both experimental and clinical pain. Smell of different types influences pain unpleasantness and intensity (the so-called qualitative measures of pain), while taste has an effect on pain threshold and tolerance (the quantitative measures) with more contradictory results. Scarce literature is reported in clinical pain and with the use of neuroimaging measures. Secondly, we performed an experimental study on healthy adults (n = 60) where we induced pain with capsaicin cream applied on the back of their hand. Such methodology has been chosen to resemble a sort of tonic neuro-pathic pain. We found evidence that pain unpleasantness is reduced after the administration of the pleasant smell condition. No effect was found on pain intensity, nor with other substances. Thirdly, we performed a very similar experimental design on a clinical population that suffers from chronic oral burning pain (n = 22), revealing that pain unpleasantness was increased by the unpleasant smell and taste sub-stances. With reference to the smell substances, such effect was related to the subjective perceived pleasantness of the patients. Moreover, a stronger effect was found in patients with longer disease duration. No effect was found on pain intensity, nor with other substances. Several clinical and psychological variables were also collected. To sum up, smell and taste could temporarily alter pain unpleasantness perception in tonic pain, both experimentally induced and in a clinical condi-tion. Future experiments that select custom-designed substances for each pa-tient could reveal a stronger effect in chronic pain populations and explore long-term efficacy. Within this frame, it is important not to forget the key role that attention and emotions play in the relation between pain and chemical senses, when exploring the effectiveness of those alternative options. The three works here described have been published in international peer reviewed journals

The impact of recurrent Covid-19 waves on patients with Functional Movement Disorders: A follow-up study

Background: Functional Movement Disorders (FMDs) might exacerbate in stressful conditions. As the global health emergency due to Covid-19 rise and multiple waves hit the Italian population, the recurrent severe restrictions' periods imposed could represent important triggers and worsen the symptoms of FMDs. Through a follow-up study, we compare results on Motor Symptoms (MS), Non-Motor Symptoms (NMS), and Global Health Status (GHS) of two surveys, one referred to the first Covid-19 wave and the other to the third Covid-19 wave. Methods: 60 FMDs patients responded to an online survey after the first and the third Covid-19 waves in Italy. Questions regarding sociodemographic, clinical and Covid-19 information, MS, NMS, and GHS were collected to assess severity of symptoms and changes in comparison to a period with less severe social restrictions. Results: Patients showed minimal to mild motor symptoms' severity, and substantial stability through time in all collected measures, both for severity and changes of MS, NMS, and GHS in comparison at two time points (p > 0.050). The worsening of pain resulted as predictor factor for the worsening of Motor Symptoms (p = 0.042). Conclusions: Patients did not show a vulnerability due to the recurrent restrictions' periods: MS, NMS and GHS did not vary in comparison to the first wave, confirming the previous results and highlighting the role of the social context in those disorders. Further investigations are required to better disentangle the relationship between stressful events, motor symptoms, and pain

Genomic characterization of Achromobacter species isolates from chronic and occasional lung infection in cystic fibrosis patients

Achromobacter species are increasingly being detected in cystic fibrosis (CF) patients, where they can establish chronic infections by adapting to the lower airway environment. To better understand the mechanisms contributing to a successful colonization by Achromobacter species, we sequenced the whole genome of 54 isolates from 26 patients with occasional and early/late chronic lung infection. We performed a phylogenetic analysis and compared virulence and resistance genes, genetic variants and mutations, and hypermutability mechanisms between chronic and occasional isolates. We identified five Achromobacter species as well as two non-affiliated genogroups (NGs). Among them were the frequently isolated Achromobacter xylosoxidans and four other species whose clinical importance is not yet clear: Achromobacter insuavis, Achromobacter dolens, Achromobacter insolitus and Achromobacter aegrifaciens. While A. insuavis and A. dolens were isolated only from chronically infected patients and A. aegrifaciens only from occasionally infected patients, the other species were found in both groups. Most of the occasional isolates lacked functional genes involved in invasiveness, chemotaxis, type 3 secretion system and anaerobic growth, whereas the great majority (>60%) of chronic isolates had these genomic features. Interestingly, almost all (n=22/23) late chronic isolates lacked functional genes involved in lipopolysaccharide production. Regarding antibiotic resistance, we observed a species-specific distribution of blaOXA genes, confirming what has been reported in the literature and additionally identifying blaOXA-2 in some A. insolitus isolates and observing no blaOXA genes in A. aegrifaciens or NGs. No significant difference in resistance genes was found between chronic and occasional isolates. The results of the mutator genes analysis showed that no occasional isolate had hypermutator characteristics, while 60% of early chronic (<1 year from first colonization) and 78% of late chronic (>1 year from first colonization) isolates were classified as hypermutators. Although all A. dolens, A. insuavis and NG isolates presented two different mutS genes, these seem to have a complementary rather than compensatory function. In conclusion, our results show that Achromobacter species can exhibit different adaptive mechanisms and some of these mechanisms might be more useful than others in establishing a chronic infection in CF patients, highlighting their importance for the clinical setting and the need for further studies on the less clinically characterized Achromobacter species

Hypermutation as an Evolutionary Mechanism for Achromobacter xylosoxidans in Cystic Fibrosis Lung Infection

Achromobacter xylosoxidans can cause chronic infections in the lungs of patients with cystic fibrosis (CF) by adapting to the specific environment. The study of longitudinal isolates allows to investigate its within\u2010host evolution to unravel the adaptive mechanisms contributing to successful colonization. In this study, four clinical isolates longitudinally collected from two chronically infected patients underwent whole genome sequencing, de novo assembly and sequence analysis. Phenotypic assays were also performed. The isolates coming from one of the patients (patient A) presented a greater number of genetic variants, diverse integrative and conjugative elements, and different protease secretion. In the first of these isolates (strain A1), we also found a large deletion in the mutS gene, involved in DNA mismatch repair (MMR). In contrast, isolates from patient B showed a lower number of variants, only one integrative and mobilizable element, no phenotypic changes, and no mutations in the MMR system. These results suggest that in the two patients the establishment of a chronic infection was mediated by different adaptive mechanisms. While the strains isolated from patient B showed a longitudinal microevolution, strain A1 can be clearly classified as a hypermutator, confirming the occurrence and importance of this adaptive mechanism in A. xylosoxidans infection

Mobilome analysis of Achromobacter spp. isolates from chronic and occasional lung infection in cystic fibrosis patients

Achromobacter spp. is an opportunistic pathogen that can cause lung infections in patients with cystic fibrosis (CF). Although a variety of mobile genetic elements (MGEs) carrying antimicrobial resistance genes have been identified in clinical isolates, little is known about the contribution of Achromobacter spp. mobilome to its pathogenicity. To provide new insights, we performed bioinformatic analyses of 54 whole genome sequences and investigated the presence of phages, insertion sequences (ISs), and integrative and conjugative elements (ICEs). Most of the detected phages were previously described in other pathogens and carried type II toxin-antitoxin systems as well as other pathogenic genes. Interestingly, the partial sequence of phage Bcep176 was found in all the analyzed Achromobacter xylosoxidans genome sequences, suggesting the integration of this phage in an ancestor strain. A wide variety of IS was also identified either inside of or in proximity to pathogenicity islands. Finally, ICEs carrying pathogenic genes were found to be widespread among our isolates and seemed to be involved in transfer events within the CF lung. These results highlight the contribution of MGEs to the pathogenicity of Achromobacter species, their potential to become antimicrobial targets, and the need for further studies to better elucidate their clinical impact

Pain, smell, and taste in adults: a narrative review of multisensory perception and interaction

Every day our sensory systems perceive and integrate a variety of stimuli containing information vital for our survival. Pain acts as a protective warning system, eliciting a response to remove harmful stimuli; it may also be a symptom of an illness or present as a disease itself. There is a growing need for additional pain-relieving therapies involving the multisensory integration of smell and taste in pain modulation, an approach that may provide new strategies for the treatment and management of pain. While pain, smell, and taste share common features and are strongly linked to emotion and cognition, their interaction has been poorly explored. In this review, we provide an overview of the literature on pain modulation by olfactory and gustatory substances. It includes adult human studies investigating measures of pain threshold, tolerance, intensity, and/or unpleasantness. Due to the limited number of studies currently available, we have structured this review as a narrative in which we comment on experimentally induced and clinical pain separately on pain-smell and pain-taste interaction. Inconsistent study findings notwithstanding, pain, smell, and taste seem to interact at both the behavioral and the neural levels. Pain intensity and unpleasantness seem to be affected more by olfactory substances, whereas pain threshold and tolerance are influenced by gustatory substances. Few pilot studies to date have investigated these effects in clinical populations. While the current results are promising for the future, more evidence is needed to elucidate the link between the chemical senses and pain. Doing so has the potential to improve and develop novel options for pain treatment

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

Cystic fibrosis (CF) lung infection is a complex condition where opportunistic pathogens and defective immune system cooperate in developing a constant cycle of infection and inflammation. The major pathogen, Pseudomonas aeruginosa, secretes a multitude of virulence factors involved in host immune response and lung tissue damage. In this study, we examined the possible anti-inflammatory effects of molecules inhibiting P. aeruginosa virulence factors

Unpleasant olfactory and gustatory stimuli increase pain unpleasantness in patients with chronic oral burning pain: an exploratory study

Background: Despite mounting evidence for the powerful influence of smell and taste substances in experimental pain, our knowledge of their effects in the clinical context is scarce, especially for patients with chronic oral burning pain. To fill this gap, we investigated the effect of olfactory and gustatory stimuli on pain perception in patients with chronic oral burning pain, a disabling condition that is difficult to manage and treat. Methods: Twenty-two patients with chronic oral burning pain underwent testing with a variety of olfactory and gustatory substances (pleasant, neutral, unpleasant) in multisensory interaction. The order of testing was randomized. Perception of pain intensity and unpleasantness was evaluated on a numerical rating scale at baseline and immediately after each test trial. Results: Pain unpleasantness but not pain intensity was found to be modulated by chemosensory stimuli. Unpleasant olfactory and gustatory stimuli increased the perception of pain unpleasantness compared to pleasant and neutral stimuli. Pain unpleasantness after unpleasant olfactory and gustatory stimuli correlated with psychological questionnaire subscale scores for distress (CORE-OM) and emotional awareness (TAS-20). Conclusions: Our findings suggest a role of unpleasant chemosensory stimuli in increasing the perception of pain unpleasantness in patients with chronic oral burning. The lack of an effect on pain intensity indicates a dissociation between sensory and affective pain components. Future research is needed to further study the association between chemosensory stimuli and emotional and subjective aspects in modulating chronic oral burning pain

DIAGNÓSTICO E PROPOSTA DE ADEQUAÇÕES ESTRATÉGICAS DE UMA FLORICULTURA DO OESTE PARANAENSE

Os levantamentos realizados por Drucker (1977) definem o planejamento estratégico como um processo contínuo, sistemático e organizado, capaz de prever o futuro, a fim de minimizar riscos. Dessa maneira, o presente relato-técnico científico objetivou desenvolver a implementação de melhorias e os usos de ferramentas gerenciais de planejamento estratégico procurando atender as necessidades formais e documentais do planejamento estratégico na empresa situada na cidade de Cascavel, Paraná. Pesquisa realizada pelo método de estudo de caso, sendo caráter qualitativo e de natureza descritiva-explicativa. Concluiu-se que a floricultura em estudo atende as solicitações evidenciadas para a elaboração do modelo de planejamento estratégico proposto por Porter (1996), e por meio de diagnóstico, por mais que a empresa não apresente em sua cultura a formalização do estudo proposto, de maneira informal há visão por parte dos gestores sobre a importância da ferramenta. Levando em consideração o levantamento da concorrência e a preocupação de elevar o nível de gestão da empresa considerando as estratégias corporativas frente aos demais players é possível observar que a empresa se encontra a frente do nicho de atuação. O estudo mostrou-se relevante, por auxiliar o empresário e gestores da empresa em diversas decisões da empresa