Unlike acute pain that warns us of injury or disease, chronic or persistent pain serves no adaptive purpose. Though there is no agreed on definition of chronic pain, it is commonly referred to as pain that is without biological value, lasting longer than the typical healing time, not responsive to treatments based on specific remedies, and of a duration greater than 6 months. Chronic pain that is severe and intractable has detrimental consequences, including psychological distress, job loss, social isolation, and, not surprisingly, it is highly comorbid with depression and anxiety. Historically, pain without an apparent anatomical or neurophysiological origin was labelled as psychopathological. This approach is damaging to the patient and provider alike. It pollutes the therapeutic relationship by introducing an element of mutual distrust as well as implicit, if not explicit, blame. It is demoralizing to the patient who feels at fault, disbelieved, and alone. Moreover, many medically unexplained pains are now understood to involve an interplay between peripheral and central neurophysiological mechanisms that have gone awry. The new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, somatic symptom disorder overpsychologizes people with chronic pain; it has low sensitivity and specificity, and it contributes to misdiagnosis, as well as unnecessary stigma. Adjustment disorder remains the most appropriate, accurate, and acceptable diagnosis for people who are overly concerned about their pain. 相似文献
To assess the public’s propensity for allergic contact dermatitis (ACD), many alternatives to in vivo chemical screening have been developed which generally incorporate a small panel of cell surface and secreted dendritic cell biomarkers. However, given the underlying complexity of ACD, one cell type and limited cellular metrics may be insufficient to predict contact sensitizers accurately. To identify a molecular signature that can further characterize sensitization, we developed a novel system using RealSkin, a full thickness skin equivalent, in co-culture with MUTZ-3 derived Langerhan’s cells. This system was used to distinguish a model moderate pro-hapten isoeugenol (IE) and a model strong pre-hapten p-phenylenediamine (PPD) from irritant, salicylic acid (SA). Commonly evaluated metrics such as CD86, CD54, and IL-8 secretion were assessed, in concert with a 27-cytokine multi-plex screen and a functional chemotaxis assay. Data were analyzed with feature selection methods using ANOVA, hierarchical cluster analysis, and a support vector machine to identify the best molecular signature for sensitization. A panel consisting of IL-12, IL-9, VEGF, and IFN-γ predicted sensitization with over 90% accuracy using this co-culture system analysis. Thus, a multi-metric approach that has the potential to identify a molecular signature may be more predictive of contact sensitization. 相似文献
Introduction: Effective antitussives available to control cough are limited. Consolidation among different afferent branches of the vagus nerve is needed to bring about cough. A general, widely accepted view is that the chronic increase in the sensitivity of the cough reflex is associated with inflammatory hypersensitivity such as from gastro-esophageal reflux disease. There is increasing evidence that an important mechanism is a sensory disorder of the laryngeal branches of the vagus nerve. Neuromodulating drugs are effectively used in the treatment of chronic pain and neuropathic disorders and may have a role in the treatment of refractory chronic cough (CC).Areas covered: Current evidence on the efficacy and safety of gabapentin in the treatment of CC is reviewed. Relevant randomized controlled trials, case reports and reviews were identified through a PubMed search of English-language literature referring to cough, sensory neuropathy and gabapentin over the last 10 years.Expert opinion: Gabapentin appears to be effective and well tolerated in the treatment of CC and in other sensory neuropathic disorders. Relevant clinical trials investigating its efficacy and safety profile in the treatment of cough are limited and further studies are needed. Gabapentin has been shown to cause minimal to no toxicity in overdose. 相似文献
Background: Hexyl cinnamal (HCA) is a widely used fragrance chemical, the low skin-sensitizing potency of which has made it a common choice for the use as a positive control for predictive toxicology assays. However, HCA is commonly negative in current candidate in vitro alternatives test methods.
Objective: To review the evidence that HCA is a classifiable skin sensitizer against the standards set by the Globally Harmonized Scheme (GHS), and determine whether it represents an appropriate choice for a positive control substance for predictive testing.
Methods: Using the GHS criteria, mechanistic data, and in vitro, in vivo and human evidence relating to HCA and skin sensitization have been reviewed.
Results: The chemistry of HCA is consistent with potential for skin sensitization and predictive in vivo test data support this conclusion. However, the human data are relatively sparse, consistent with HCA possessing a low capacity to induce skin sensitization under conditions of consumer exposures.
Conclusions: Using GHS criteria (and applying a precautionary approach) HCA would classify as a weaker skin sensitizer than predicted by the local lymph node assay (LLNA). However, given the human experience, it is necessary to consider whether HCA is the most appropriate choice for use as a positive regulatory control. 相似文献
Objective: To evaluate the effectiveness and safety of AHP with or without CT for people with COPD at stable stage.
Methods: We searched randomized controlled trials comparing AHP (with or without CT) with no intervention, placebo, or CT from six
databases. Two authors selected studies, extracted data and evaluated risk of bias of included trials. RevMan 5.2 software was used to
analysis data.
Results: Twenty one RCTs (2327 participants) were included. AHP of non-sanfu applied on no fixed dates with CT significantly decreased
the mean frequency of acute exacerbation of COPD (times per year) (MD: ?1.24; 95% CI: ?2.02 to ?0.46; 2 trials), and improved the lung
function parameters and quality of life. The AHP with CT showed no better effect in 6-minute walking distance (6MWD) and hospitalization.
In addition, AHP applied at sanfu (specific dates based on lunar calendar) with CT had significant effect for 6MWD. One trial reported skin
irritation and found no significant difference between two groups. Another trial reported two patients had eyes discomfort, which was inferred
as the adverse effects of seretide.
Conclusion: AHP used as adjunct to CT, appears to be effective than CT alone in patients with stable COPD. However, further large,
rigorously designed trials are warranted to confirm these potential effects. 相似文献