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Current Oncology (Toronto, Ont.) Jul 2023Pain is frequently reported during cancer disease, and it still remains poorly controlled in 40% of patients. Recent developments in oncology have helped to better... (Review)
Review
Pain is frequently reported during cancer disease, and it still remains poorly controlled in 40% of patients. Recent developments in oncology have helped to better control pain. Targeted treatments may cure cancer disease and significantly increase survival. Therefore, a novel population of patients (cancer survivors) has emerged, also enduring chronic pain (27.6% moderate to severe pain). The present review discusses the different options currently available to manage pain in (former) cancer patients in light of progress made in the last decade. Major progress in the field includes the recent development of a chronic cancer pain taxonomy now included in the International Classification of Diseases (ICD-11) and the update of the WHO analgesic ladder. Until recently, cancer pain management has mostly relied on pharmacotherapy, with opioids being considered as the mainstay. The opioids crisis has prompted the reassessment of opioids use in cancer patients and survivors. This review focuses on the current utilization of opioids, the neuropathic pain component often neglected, and the techniques and non-pharmacological strategies available which help to personalize patient treatment. Cancer pain management is now closer to the management of chronic non-cancer pain, i.e., "an integrative and supportive pain care" aiming to improve patient's quality of life.
Topics: Humans; Analgesics, Opioid; Chronic Pain; Quality of Life; Cancer Pain; Pain Management; Neoplasms
PubMed: 37504360
DOI: 10.3390/curroncol30070500 -
Nature Communications Jun 2023Voltage-gated sodium (Na) channels are targeted by a number of widely used and investigational drugs for the treatment of epilepsy, arrhythmia, pain, and other...
Voltage-gated sodium (Na) channels are targeted by a number of widely used and investigational drugs for the treatment of epilepsy, arrhythmia, pain, and other disorders. Despite recent advances in structural elucidation of Na channels, the binding mode of most Na-targeting drugs remains unknown. Here we report high-resolution cryo-EM structures of human Na1.7 treated with drugs and lead compounds with representative chemical backbones at resolutions of 2.6-3.2 Å. A binding site beneath the intracellular gate (site BIG) accommodates carbamazepine, bupivacaine, and lacosamide. Unexpectedly, a second molecule of lacosamide plugs into the selectivity filter from the central cavity. Fenestrations are popular sites for various state-dependent drugs. We show that vinpocetine, a synthetic derivative of a vinca alkaloid, and hardwickiic acid, a natural product with antinociceptive effect, bind to the III-IV fenestration, while vixotrigine, an analgesic candidate, penetrates the IV-I fenestration of the pore domain. Our results permit building a 3D structural map for known drug-binding sites on Na channels summarized from the present and previous structures.
Topics: Humans; Analgesics; Carbamazepine; Lacosamide; Pain; Protein Domains; Voltage-Gated Sodium Channels; Voltage-Gated Sodium Channel Blockers
PubMed: 37270609
DOI: 10.1038/s41467-023-38942-3 -
Brain : a Journal of Neurology Sep 2023Chronic pain affects millions of people worldwide and new treatments are needed urgently. One way to identify novel analgesic strategies is to understand the biological...
Chronic pain affects millions of people worldwide and new treatments are needed urgently. One way to identify novel analgesic strategies is to understand the biological dysfunctions that lead to human inherited pain insensitivity disorders. Here we report how the recently discovered brain and dorsal root ganglia-expressed FAAH-OUT long non-coding RNA (lncRNA) gene, which was found from studying a pain-insensitive patient with reduced anxiety and fast wound healing, regulates the adjacent key endocannabinoid system gene FAAH, which encodes the anandamide-degrading fatty acid amide hydrolase enzyme. We demonstrate that the disruption in FAAH-OUT lncRNA transcription leads to DNMT1-dependent DNA methylation within the FAAH promoter. In addition, FAAH-OUT contains a conserved regulatory element, FAAH-AMP, that acts as an enhancer for FAAH expression. Furthermore, using transcriptomic analyses in patient-derived cells we have uncovered a network of genes that are dysregulated from disruption of the FAAH-FAAH-OUT axis, thus providing a coherent mechanistic basis to understand the human phenotype observed. Given that FAAH is a potential target for the treatment of pain, anxiety, depression and other neurological disorders, this new understanding of the regulatory role of the FAAH-OUT gene provides a platform for the development of future gene and small molecule therapies.
Topics: Humans; RNA, Long Noncoding; Pain; Analgesics; Ganglia, Spinal
PubMed: 37222214
DOI: 10.1093/brain/awad098 -
British Journal of Sports Medicine Aug 2023Clinical guidelines recommend exercise as a core treatment for knee or hip osteoarthritis (OA). However, how its analgesic effect compares to analgesics, for example,... (Meta-Analysis)
Meta-Analysis
Comparative efficacy of exercise therapy and oral non-steroidal anti-inflammatory drugs and paracetamol for knee or hip osteoarthritis: a network meta-analysis of randomised controlled trials.
OBJECTIVE
Clinical guidelines recommend exercise as a core treatment for knee or hip osteoarthritis (OA). However, how its analgesic effect compares to analgesics, for example, oral non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol-the most commonly used analgesics for OA, remains unknown.
DESIGN
Network meta-analysis.
DATA SOURCES
PubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA.
RESULTS
A total of n=152 RCTs (17 431 participants) were included. For pain relief, there was no difference between exercise and oral NSAIDs and paracetamol at or nearest to 4 (standardised mean difference (SMD)=-0.12, 95% credibility interval (CrI) -1.74 to 1.50; n=47 RCTs), 8 (SMD=0.22, 95% CrI -0.05 to 0.49; n=2 RCTs) and 24 weeks (SMD=0.17, 95% CrI -0.77 to 1.12; n=9 RCTs). Similarly, there was no difference between exercise and oral NSAIDs and paracetamol in functional improvement at or nearest to 4 (SMD=0.09, 95% CrI -1.69 to 1.85; n=40 RCTs), 8 (SMD=0.06, 95% CrI -0.20 to 0.33; n=2 RCTs) and 24 weeks (SMD=0.05, 95% CrI -1.15 to 1.24; n=9 RCTs).
CONCLUSIONS
Exercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol.CRD42019135166.
Topics: Aged; Humans; Acetaminophen; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Exercise Therapy; Network Meta-Analysis; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain; Randomized Controlled Trials as Topic
PubMed: 36593092
DOI: 10.1136/bjsports-2022-105898 -
Frontiers in Immunology 2023Clinical observations have found that prolonged use of analgesics increases the incidence of infection. However, the direct causal relationship between prescription...
INTRODUCTION
Clinical observations have found that prolonged use of analgesics increases the incidence of infection. However, the direct causal relationship between prescription analgesic use (PAU) and risk of infection (ROI) remains unclear.
METHODS
This study used Mendelian randomization (MR) design to estimate the causal effect of PAU on ROI, as well as their mediating factors. Genetic data on prescription analgesics use and immune cells were obtained from published GWAS. Additionally, data on ROI were extracted from the FinnGen database. Two-sample MR analysis and multivariate MR (MVMR) analysis were performed using inverse variance weighting (IVW) to ascertain the causal association between PAU and ROI. Finally, 731 immune cell phenotypes were analyzed for their mediating role between analgesics and infection.
RESULTS
Using two-sample MR, IVW modeling showed that genetically predicted opioid use was associated with increased risk of pulmonary infection (PI) (OR = 1.13, 95% CI: 1.05-1.21, 0.001) and upper respiratory infection (URI) (OR = 1.18, 95% CI: 1.08-1.30, 0.001); non-steroidal anti-inflammatory drugs (NSAIDs) were related to increased risk of skin and subcutaneous tissue infection (OR = 1.21, 95% CI: 1.05-1.39, = 0.007), and antimigraine preparations were linked to a reduced risk of virus hepatitis (OR = 0.79, 95% CI: 0.69-0.91, 0.001). In MVMR, the association of opioids with URI and PI remained after accounting for cancer conditions. Even with a stricter threshold ( 0.05/30), we found a significant causal association between opioids and respiratory infections (URI/PI). Finally, mediation analyses found that analgesics influence the ROI through different phenotypes of immune cells as mediators.
CONCLUSION
This MR study provides new genetic evidence for the causal relationship between PAU and ROI, and the mediating role of immune cells was demonstrated.
Topics: Humans; Mendelian Randomization Analysis; Analgesics; Analgesics, Opioid; Immunologic Factors; Prescriptions; Respiratory Tract Infections; Communicable Diseases
PubMed: 38193081
DOI: 10.3389/fimmu.2023.1319127 -
Swiss Dental Journal Sep 2023
Topics: Humans; Analgesics, Opioid; Dental Care
PubMed: 37641473
DOI: No ID Found -
Acta Bio-medica : Atenei Parmensis Aug 2023Differently from the adult patients, in paediatric age it is more difficult to assess and treat efficaciously the pain and often this symptom is undertreated or not... (Review)
Review
Differently from the adult patients, in paediatric age it is more difficult to assess and treat efficaciously the pain and often this symptom is undertreated or not treated. In children, a selection of appropriate pain assessment tools should consider the age, the cognitive level, the presence of eventual disability, the type of pain and the situation in which it is occurring. Improved understanding of developmental neurobiology and paediatric analgesic drug pharmacokinetics should facilitate a better management of childhood pain. The objective of this update is to discuss the current practice and the recent advances in pediatric pain management. Using PubMed and the Cochrane Library we conducted an extensive literature analysis on pediatric pain assessment and commonly used analgesic agents in this kind of patients. According to our results, a multimodal analgesic regimen provides a better pain control and a functional outcome in children. Cooperation and communication among the anaesthesiologist, the surgeon and the paediatrician remains essential for successful anaesthesia and pain management in childhood.
Topics: Adult; Child; Humans; Analgesics; Communication; Pain; Pain Management; Pain Measurement
PubMed: 37539605
DOI: 10.23750/abm.v94i4.14289 -
CMAJ : Canadian Medical Association... Mar 2024
Topics: Humans; Analgesics, Opioid; Narcotics; Substance Withdrawal Syndrome
PubMed: 38527744
DOI: 10.1503/cmaj.230968-f -
Ugeskrift For Laeger Jan 2024Chronic malignant pain is a common and feared condition. Especially, since many patients do not achieve proper pain relief from conventional peroral medication regimes... (Review)
Review
Chronic malignant pain is a common and feared condition. Especially, since many patients do not achieve proper pain relief from conventional peroral medication regimes and possible unacceptable side effects of high dosing. As argued in this review, in these patients, continuous intrathecal infusion of pain medicine by a programmable subcutaneously placed pump enables good pain relief, less systemic side effects, and better life quality. Intrathecal pain treatment should therefore be considered in patients with a proper performance score and suitable estimated life expectancy.
Topics: Humans; Morphine; Analgesics; Palliative Care; Pain Management; Pain; Chronic Pain
PubMed: 38305326
DOI: 10.61409/V08230541 -
Ugeskrift For Laeger Apr 2024In the last decade, patients with chronic pain have expressed increasing interest in cannabis-derived products for adjuvant therapy when treatment is deemed refractory... (Review)
Review
In the last decade, patients with chronic pain have expressed increasing interest in cannabis-derived products for adjuvant therapy when treatment is deemed refractory to conventional analgesics. At present, clinical evidence to support this treatment approach appears to be sparse. Not because clinical studies as such are lacking, but rather as a result of methodological bias in relation to study design, patient populations, and treatment protocols. In this review, research in cannabis medicine for relief of chronic pain is reviewed, mainly with reference to published meta-analytic studies.
Topics: Humans; Chronic Pain; Medical Marijuana; Dronabinol; Analgesics
PubMed: 38708699
DOI: 10.61409/V08230546