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While ketamine's analgesia has mostly been attributed to antagonism of N-methyl-D-aspartate receptors, evidence suggests multiple other pathways are involved in its antidepressant and possibly analgesic activity. These mechanisms and ketamine's role in the nociplastic pain paradigm are discussed. Animal studies demonstrating ketamine's neurotoxicity have unclear human translatability and findings from key rodent and human studies are presented.
Learn More >Chronic constriction injury (CCI) of the sciatic nerve was used to establish neuropathic pain (NP) models in rats. CCI rats were then treated with propofol and their paw withdrawal mechanical threshold (PWMT) and paw withdraw thermal latency (PWTL) were measured. In addition, the expression patterns of TNF-α, IL-1β and IL-10 were detected. CCI rats treated with propofol were further injected with antagomiR-140-3p to verify the role of miR-140-3p in propofol's analgesic actions. In addition to confirming the relationship between miR-140-3p and JAG1, the expression patterns of JAG1 itself were detected. Propofol-treated CCI rats were also injected with Ad-JAG1 to test the role of JAG1 in propofol's analgesic mechanism of action. Finally, the levels of JAG1 and Notch pathway-related proteins were detected.Results: Propofol was found to alleviate NP, including thermal hyperalgesia and mechanical pain threshold. Propofol could also ameliorate neuroinflammation by up-regulating the expression of IL-10 and inhibiting the release of TNF-α and IL-1β. Mechanically, propofol enhanced the amount of miR-140-3p in CCI rats via regulation of JAG1. Down-regulation of miR-140-3p, or up-regulation of JAG1, could reduce the protective effect of propofol against NP. Propofol inhibited the activation of Notch signaling via miR-140-3p/JAG1 to realize its analgesic effect. Conclusion: Our findings indicated that propofol inhibits inflammatory responses and the Notch signaling pathway via miR-140-3p/JAG1 to alleviate NP. These data provide evidence to support a potential clinical therapy for NP. This article is protected by copyright. All rights reserved.
Learn More >Little is known about the factors that influence providers' perceptions of patient risk for aberrant opioid use. Patient gender may interact with prior opioid misuse to influence these perceptions. We asked 131 physicians to view videos and vignettes for 8 virtual patients with chronic pain. Gender (male/female) and previous prescription opioid misuse (present/absent) varied across patients; the vignettes were otherwise balanced on demographic and clinical characteristics. For each patient, providers assessed four risk domains: opioid-related adverse events, opioid misuse/abuse, opioid addiction, and opioid diversion. Results indicated a significant gender-by-misuse interaction for risk of opioid misuse/abuse. When previous misuse behaviors were absent, providers rated men at higher risk; there was no gender difference when previous misuse behaviors were present. A significant gender-by-misuse interaction was found for risk of opioid-related adverse events. Providers perceived men to be higher risk when previous misuse behaviors were absent; there was no gender difference when previous misuse behaviors were present. A significant gender-by-misuse interaction was found for risk of opioid addiction. Providers rated women at higher risk when previous misuse behaviors were present, and men at higher risk when previous misuse behaviors were absent. There were significant main effects of gender and misuse for risk of opioid diversion. Providers rated men and those with previous misuse behaviors at higher risk. These results demonstrate that patient gender and previous opioid misuse have unique and interactive effects on provider perceptions of prescription opioid-related risks. Studies are needed to identify the mechanisms underlying these effects, such as gender-based stereotypes about risk-taking and drug abuse.
Learn More >Chronic pain represents one of the most serious worldwide medical problems, in terms of both social and economic costs, often causing severe and intractable physical and psychological suffering. The lack of biological markers for pain, which could assist in forming clearer diagnoses and prognoses, makes chronic pain therapy particularly arduous and sometimes harmful. Opioids are used worldwide to treat chronic pain conditions, but there is still an ambiguous and inadequate understanding about their therapeutic use, mostly because of their dual effect in acutely reducing pain and inducing, at the same time, tolerance, dependence, and a risk for opioid use disorder. In addition, clinical studies suggest that opioid treatment can be associated with a high risk of immune suppression and the development of inflammatory events, worsening the chronic pain status itself. While opioid peptides and receptors are expressed in both central and peripheral nervous cells, immune cells, and tissues, the role of opioids and their receptors, when and why they are activated endogenously and what their exact role is in chronic pain pathways is still poorly understood. Thus, in this review we aim to highlight the interplay between pain and immune system, focusing on opioids and their receptors.
Learn More >High-frequency rTMS over the dorsolateral prefrontal cortex (DLPFC) has demonstrated mixed effects on chronic and provoked pain.
Learn More >Erenumab is a monoclonal antibody acting against calcitonin gene-related peptide receptor and approved for the preventive treatment of chronic migraine. The aim of the present study is to identify clinical predictors of good response in patients with chronic migraine and medication overuse-headache.
Learn More >Reliable, clinic-friendly screening for Chronic postsurgical pain (CPSP) risk is unavailable. Within a prospective, observational study, we evaluated Pediatric Pain Screening Tool (PPST), a concise 9-item questionnaire, as a preoperative screening tool to identify those at higher risk for CPSP (NRS>3/10 beyond three months post-surgery) and poor function (disability/FDI/quality of life/PedsQL)) after spine fusion and Nuss procedures. Incidence of CPSP was 34.86% (38/109). We confirmed PPST scale stability, test re-test reliability (ICC=0.68;p<0.001); PPST measures were positively correlated with known CPSP risk factors (p<0.001) (preoperative pain (SCC:0.672), CASI (SCC:0.357), PROMIS pain interference (SCC:0.569), PROMIS depression (SCC:0.501), PedsQL (SCC:-0.460) and insomnia severity index (SCC0.567). Preoperative PPST and PPST physical sub-scores (median(IQR) were higher in CPSP (2(0.5,4), 1(0,2)) compared to non-CPSP ((1(0,3), 0(0,1.5)) groups (p=0.026, p=0.029) respectively. PPST scores/sub-scores positively correlated with higher FDI at 6 months but only PPST total and PPST psychosocial subscore correlated with higher FDI at 12 months. Based on ROC, optimal PPST cutoff for CPSP was 2 (63.9% sensitivity, 64.7% specificity). CPSP risk was high (48.94% risk) if PPST ≥ 2 (n=47) and medium (22.81%) if PPST<2 (n=57) after spine/pectus surgery. General and risk-strata specific, targeted psychosocial non-pharmacological interventions, need to be studied. Findings need validation in diverse, larger cohorts. CLINICALTRIALS.GOV IDENTIFIER: NCT02998138 PERSPECTIVE: The article supports Pediatric Pain Screening Tool, a simple 9-item questionnaire, as a preoperative screening tool for chronic post-surgical pain (CPSP) and function 6-12 months after spine/pectus surgeries. PPST measures correlate with known risk factors for CPSP. Risk stratification and targeted preventive interventions in high-risk subjects are proposed.
Learn More >Chronic pain and depression are highly comorbid and difficult-to-treat disorders. We previously showed this comorbidity is associated with higher depression severity, lower antidepressant treatment effectiveness and poorer prognosis in the Australian Genetics of Depression Study.
Learn More >The aim of the present study was to investigate the role of cognitive processing biases in Type 2 diabetes (T2D) and chronic pain, two conditions that are highly co-morbid. The final sample comprised 333 individuals (86 with T2D and chronic pain, 65 with chronic pain, 76 with T2D, 106 without any form of diabetes or pain). Participants completed questionnaires assessing pain and diabetes-related outcomes, as well as measures of interpretation bias, attentional bias, and attentional bias variability. In a 2 (pain status) x 2 (T2D status) x 3 (bias valence) ANOVA design, interpretation biases were found to be stronger in individuals with chronic pain than individuals without pain, although there were no differences according to T2D status. No group differences in attentional biases were found. Among individuals with T2D, greater interpretation bias was associated with better blood glucose control, but also greater fear of hypoglycaemia. For individuals with chronic pain, greater interpretation bias and attentional bias variability was associated with worse pain outcomes.. Whilst interpretation bias may be present in chronic pain, it also appears to indicate better glycaemic control in individuals with T2D. These findings suggest a more dynamic approach to understanding cognitive bias is needed, to consider when these biases are more or less adaptive, so that they can be better harnessed to improve outcomes for individuals with T2D who experience chronic pain. Perspective: These findings suggest that cognitive biases can be associated with psychopathology in chronic pain and in T2D, but can also potentially be adaptive in those with T2D. Diabetes management interventions may require a careful balance between promoting sufficient concern to motivate engagement in adaptive diabetes self-management, whilst also minimising fear of hypoglycaemia.
Learn More >Calcitonin gene-related peptide plasma levels have frequently been determined as a biomarker for primary headaches. However, published data is often inconsistent resulting from different methods that are not precisely described in most studies.
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