Treatment Of Pain In People Research Articles

Impact of Vaso-Occlusive Crises on the Transcriptomes of Patients with Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is an inherited, multisystem blood disorder that affects millions of people worldwide and is particularly common among those of African descent. Vaso-occlusive crises (VOCs) or acute pain events involving complex interactions among sickled erythrocytes, endothelial cells, leukocytes, and activated platelets are hallmark symptoms of SCD. Over time, episodic bouts of acute VOC may develop into chronic pain, defined as pain most days for 6 months. At present, there are no biomarkers that distinguish between acute and chronic pain. Here, we explore differences in gene expression during VOC events in a cohort of pediatric patients with SCD. The objective of this study was to examine transcriptome alterations in CD45+ cells of individuals with SCD during a VOC event compared with steady state (SS) in patients with or without chronic pain. Methods: Patients were aged <21 years, with HbSS or HbSβ 0 genotypes. Informed consent was obtained for all patients. CD45+ cell (lymphohematopoietic lineage) samples were collected from 158 patients with SCD under SS conditions (at the maximum tolerated dose of hydroxyurea; some patients were also on metformin) during a VOC event, and at a follow-up visit after a VOC. RNA sequencing (RNA-Seq) was performed using a 101-base pair, paired-end protocol run on the NovaSeq 6000 system. We applied supervised normalization of microarrays to adjust the normalized gene expression values for the effect of multiple covariates. ToppGene Suite was used for over-representation analysis (ORA; Chen et al. Nucleic Acid Res 2009). Analysis of differentially expressed genes was performed using limma software and gene set enrichment analysis using the Molecular Signature Database. Results: A summary of the study cohort is presented (Table). Most patients (98.7%) were on hydroxyurea. We collected RNA-Seq data from unpaired and paired samples at SS and during a VOC. After adjusting for age, sex, chronic pain status, and metformin status, analyses of RNA-Seq data showed upregulated genes linked to TNFα signaling via NFΚB, IL-6/JAK/STAT3 signaling, complement activation, and coagulation were enriched in CD45+ cells during VOCs compared with SS (Figure). Differentially expressed genes were also compared with whole blood transcriptome samples collected at baseline and during a VOC event as reported by Creary et al (Sci Rep 2020). Approximately 290 upregulated and 33 downregulated genes were shared in both studies. ORA analysis of the shared genes revealed upregulation of pathways such as neutrophil degranulation and complement activation during a VOC event. Analysis of samples from patients without chronic pain at SS indicated similar immune-related pathways, such as complement activation and interferon α response, were upregulated during a VOC event. In contrast, analysis of samples from patients reporting chronic pain revealed no significant differences in gene expression between a VOC event and SS. Conclusions: Samples collected during a VOC event showed significant changes in the transcriptome of CD45+ cells compared with SS in pediatric patients who had the most severe disease, or sickle cell anemia characterized by HbSS and HBSβ 0/+ genotypes, without a diagnosis of chronic pain, with multiple pathways altered by VOC. However, when VOC transcriptomes in patients with chronic pain were compared with SS, these pathways were not significantly altered. Our pediatric patient population had low rates of chronic pain; therefore, our sample size was limited. Additional analyses of SS and VOC transcriptomes, particularly in patients with chronic pain, will expand our understanding of the impact of VOC events on transcriptomes in individuals with and without chronic pain. This may lead to identification of quantitative biomarkers for a VOC, facilitating testing of new therapies for the treatment of pain in people with SCD.

Efficacy of Fluoxetine, Riluzole and Amiloride in treating neuropathic pain associated with secondary progressive multiple sclerosis. Pre-specified analysis of the MS-SMART double-blind randomised placebo-controlled trial

BackgroundEvidence-based treatment of pain in people with MS presents a major unmet need. ObjectiveWe aimed to establish if use of Fluoxetine, Riluzole or Amiloride improved neuropathic pain outcomes in comparison to placebo, in adults with secondary progressive MS participating in a trial of these putative neuroprotectants. MethodsIn pre-specified secondary analyses of the MS SMART phase-2b double-blind randomised controlled trial (NCT01910259), we analyzed reports of neuropathic pain, overall pain, and pain interference. Multivariate analyses included adjustment for baseline pain severity. Additionally, we explored associations of pain severity with clinical and MRI brain imaging variables. Results445 Participants were recruited from 13 UK neuroscience centres. We found no statistically significant benefit of active intervention on any rating of neuropathic pain, or pain overall. Compared to placebo, adjusted mean difference in pain intensity was 0.38 (positive values favouring placebo, 95%CI -0.30 to 1.07, p = 0.27) for Amiloride; 0.52 (-0.17 to 1.22, p = 0.14) for Fluoxetine; and 0.40 (-0.30 to 1.10, p = 0.26) for Riluzole. Pain severity was positively correlated with depressive symptoms (Spearman correlation 0.19, 95%CI 0.10–0.28) and fatigue (Rho 0.30, 95%CI 0.20–0.39). ConclusionUse of Fluoxetine, Riluzole or Amiloride was not associated with improvement in neuropathic pain symptoms, in comparison to placebo.

The Role of Nurses' Uncertainty in Decision-Making Process of Pain Management in People with Dementia.

Pain in people with dementia (PWD) is underassessed and undertreated. Treatment of pain in people with dementia goes awry because of poor assessment, poor treatment, and factors related to nursing decision-making skills. Several theoretical models addressed the role of nurses' critical thinking and decision-making skills in pain treatment, like the cognitive continuum theory (CCT) and the adaptive pain management (APT). Only the Response to Certainty of Pain (RCP) model was the first model to posit relationships between nurses' uncertainty, pain assessment, and patient outcomes. Gilmore-Bykovskyi and Bowers developed the RCP, which incorporates the concept of uncertainty and how it relates to the problem of unrelieved pain in PWD. The RCP model has the potential to provide good understanding of the problem of unrelieved pain in people with dementia. It also could help to develop a research study that brings comfort to an often neglected and vulnerable population.

Celostni pristop k ugotavljanju in obravnavi bolečine pri obolelih za demenco: na dokazih podprta priporočila za dobro prakso

Uvod: Neustrezna obravnava bolečine pri obolelih za demenco je neposredno povezana s slabšim kognitivnim funkcioniranjem, izgubo komunikacijskih sposobnosti ter omejitvami pri izražanju bolečine. Namen prispevka je predstavitev znanstvenih dokazov s področja ocene bolečine pri obolelih za demenco.
 Metode: Uporabljen je sistematični pregled znanstvene in strokovne literature, omejene na objave v angleščini, nemščini in slovenščini ter izdajo v časovnem obdobju 2007-2013. Izbor člankov je bil določen glede na naslednje kriterije: dostopnost, znanstvenost, vsebinska ustreznost in aktualnost. Podatki so bili po izboru obdelani s kvalitativno vsebinsko analizo.
 Rezultati: Z vsebinsko analizo 16 znanstvenih besedil so podana temeljna izhodišča za oceno in obravnavo bolečine pri obolelih za demenco. Tako je bilo identificiranih pet vsebinskih kategorij: razlogi za bolečino, spremljajoči znaki, instrumenti za ugotavljanje bolečine, zdravstvena obravnava in vloga medicinske sestre.
 Diskusija in zaključek: Priporoča se, da se ocena bolečine pri obolelih za demenco obravnava celostno v kontekstu vedenjskih motenj, funkcioniranja in življenjskih pogojev. Na podlagi izsledkov bi bilo potrebno za obolele za demenco uporabiti primeren instrumentarij, ki bo del standarda kakovostne obravnave, saj obstajajo omejitve v zvezi s preverjanjem v klinični praksi.

Correction: Assessment and treatment of pain in people with dementia

Nat. Rev. Neurol. 8, 264–274 (2012); doi:10.1038/nrneurol.2012.53 In the version of this article initially published, information was omitted from the acknowledgement section. The error has been corrected in the HTML and PDF versions of the article.

Discomfort in dementia: identifying and managing pain

Discomfort in dementia: identifying and managing pain

Assessment and treatment of pain in people with dementia

Many elderly people experience pain and regularly take analgesic medication. Pain is also frequent in people with dementia, particularly those with severe disease. As no robust clinical guidelines are available for the treatment of pain in the context of dementia, the risk of inadequate treatment in individuals with this condition is high. Furthermore, our understanding of the aetiology of pain and the potential role of dementia-associated neuropathology in pain is limited. These issues are important in the clinical management of individuals with dementia, as untreated pain is a major contributor to reduced quality of life and disability, and can lead to increased behavioural and psychological symptoms. Assessment scales to identify pain in people with dementia have been highlighted in recent studies, but there is little evidence for consistency between these tools. Numerous studies have evaluated various approaches for the treatment of pain, including stepped-care protocols and/or administration of paracetamol and opioid medications. In this Review, we summarize the best-available evidence regarding the aetiology, assessment and treatment of pain in people with dementia. Further validation of assessment tools and large-scale trials of treatment approaches in people with dementia are needed to improve clinical guidance for the treatment of pain in these individuals.

Hydrotherapy for the Treatment of Pain in People with Multiple Sclerosis: A Randomized Controlled Trial

Background. Multiple sclerosis (MS) is a chronic demyelinating neurological disease. Several studies have reported that complementary and alternative therapies can have positive effects against pain in these patients. Objective. The objective was to investigate the effectiveness of an Ai-Chi aquatic exercise program against pain and other symptoms in MS patients. Methods. In this randomized controlled trial, 73 MS patients were randomly assigned to an experimental or control group for a 20-week treatment program. The experimental group underwent 40 sessions of Ai-Chi exercise in swimming pool and the control group 40 sessions of abdominal breathing and contraction-relaxation exercises in therapy room. Outcome variables were pain, disability, spasm, depression, fatigue, and autonomy, which were assessed before the intervention and immediately and at 4 and 10 weeks after the last treatment session. Results. The experimental group showed a significant (P < 0.028) and clinically relevant decrease in pain intensity versus baseline, with an immediate posttreatment reduction in median visual analogue scale scores of 50% that was maintained for up to 10 weeks. Significant improvements were also observed in spasm, fatigue, disability, and autonomy. Conclusion. According to these findings, an Ai-Chi aquatic exercise program improves pain, spasms, disability, fatigue, depression, and autonomy in MS patients.