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Molecular Basis of Cancer Pain Management: An Updated Review.

ABSTRACT: Pain can have a significantly negative impact on the quality of life of patients. Therefore, patients may resort to analgesics to relieve the pain. The struggle to manage pain in cancer patients effectively and safely has long been an issue in medicine. Analgesics are the mainstay treatment for pain management as they act through various methods on the peripheral and central pain pathways. However, the variability in the patient genotypes may influence a drug response and adverse drug effects that follow through. This review summarizes the observed effects of analgesics on UDP-glucuronosyl (UGT) 2B7 isoenzyme, cytochrome P450 (CYP) 2D6, ?-opioid receptor ? 1 (OPRM1), efflux transporter P-glycoprotein (P-gp) and ATP-binding cassette B1 ABCB1/multiple drug resistance 1 (MDR1) polymorphisms on the mechanism of action of these drugs in managing pain in cancer. Furthermore, this review article also discusses the responses and adverse effects caused by analgesic drugs in cancer pain management, due to the inter-individual variability in their genomes.

SUBMITTER: V Subramaniam A

PROVIDER: S-EPMC6780247 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Molecular Basis of Cancer Pain Management: An Updated Review.

V Subramaniam Ayappa A Salem Yehya Ashwaq Hamid AH Oon Chern Ein CE

Medicina (Kaunas, Lithuania) 20190912 9

Pain can have a significantly negative impact on the quality of life of patients. Therefore, patients may resort to analgesics to relieve the pain. The struggle to manage pain in cancer patients effectively and safely has long been an issue in medicine. Analgesics are the mainstay treatment for pain management as they act through various methods on the peripheral and central pain pathways. However, the variability in the patient genotypes may influence a drug response and adverse drug effects th ...[more]

PMID: 31547335

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Project description:Caesarean section is associated with moderate-to-severe postoperative pain, which can influence postoperative recovery and patient satisfaction as well as breastfeeding success and mother-child bonding. The aim of this systematic review was to update the available literature and develop recommendations for optimal pain management after elective caesarean section under neuraxial anaesthesia. A systematic review utilising procedure-specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials published in the English language between 1 May 2014 and 22 October 2020 evaluating the effects of analgesic, anaesthetic and surgical interventions were retrieved from MEDLINE, Embase and Cochrane databases. Studies evaluating pain management for emergency or unplanned operative deliveries or caesarean section performed under general anaesthesia were excluded. A total of 145 studies met the inclusion criteria. For patients undergoing elective caesarean section performed under neuraxial anaesthesia, recommendations include intrathecal morphine 50-100 µg or diamorphine 300 µg administered pre-operatively; paracetamol; non-steroidal anti-inflammatory drugs; and intravenous dexamethasone administered after delivery. If intrathecal opioid was not administered, single-injection local anaesthetic wound infiltration; continuous wound local anaesthetic infusion; and/or fascial plane blocks such as transversus abdominis plane or quadratus lumborum blocks are recommended. The postoperative regimen should include regular paracetamol and non-steroidal anti-inflammatory drugs with opioids used for rescue. The surgical technique should include a Joel-Cohen incision; non-closure of the peritoneum; and abdominal binders. Transcutaneous electrical nerve stimulation could be used as analgesic adjunct. Some of the interventions, although effective, carry risks, and consequentially were omitted from the recommendations. Some interventions were not recommended due to insufficient, inconsistent or lack of evidence. Of note, these recommendations may not be applicable to unplanned deliveries or caesarean section performed under general anaesthesia.

Project description:BackgroundPain ratings reported by patients with cancer continue to increase, and numerous computer and phone apps for managing cancer-related pain have been developed recently; however, whether these apps effectively alleviate patients' pain remains unknown.ObjectiveThis study aimed to comprehensively evaluate the role of mobile apps in the management of cancer pain.MethodsLiterature on the use of apps for cancer pain management and interventions, published before August 2019, was retrieved from the following databases: MEDLINE, Embase, Cochrane, CINAHL, Scopus, and PsycINFO. The effects of apps on cancer pain were evaluated using RevMan5.3 software, and the rates of adverse drug reactions were analyzed using the R Statistical Software Package 3.5.3.ResultsA total of 13 studies were selected for the analysis: 5 randomized controlled trials (RCTs), 4 before-after studies, 2 single-arm trials, 1 prospective cohort study, and 1 prospective descriptive study. The 5 RCTs reported data for 487 patients (240 patients in the intervention group and 247 patients in the control group), and the remaining studies reported data for 428 patients. We conducted a meta-analysis of the RCTs. According to the meta-analysis, apps can significantly reduce pain scores (mean difference [MD]=-0.50, 95% CI -0.94 to -0.07, I2=62%, P=.02). We then used apps that have an instant messaging module for subgroup analysis; these apps significantly reduced patients' pain scores (MD=-0.67, 95% CI -1.06 to -0.28, I2=57%, P<.01). Patients using apps without an instant messaging module did not see a reduction in the pain score (MD=0.30, 95% CI -1.31 to 1.92, I2=70%, P=.71). Overall, patients were highly satisfied with using apps. Other outcomes, such as pain catastrophizing or quality of life, demonstrated greater improvement in patients using apps with instant messaging modules compared with patients not using an app.ConclusionsThe use of apps with instant messaging modules is associated with reduced pain scores in patients with cancer-related pain, and patient acceptance of these apps is high. Apps without instant messaging modules are associated with relatively higher pain scores. The presence of an instant messaging module may be a key factor affecting the effect of an app on cancer pain.

Project description:Recurrent, metastatic disease represents the most frequent cause of death for patients with thyroid cancer, and radioactive iodine (RAI) remains a mainstay of therapy for these patients. Unfortunately, many thyroid cancer patients have tumors that no longer trap iodine, and hence are refractory to RAI, heralding a poor prognosis. RAI-refractory (RAI-R) cancer cells result from the loss of thyroid differentiation features, such as iodide uptake and organification. This loss of differentiation features correlates with the degree of mitogen-activated protein kinase (MAPK) activation, which is higher in tumors with BRAF (B-Raf proto-oncogene) mutations than in those with RTK (receptor tyrosine kinase) or RAS (rat sarcoma) mutations. Hence, inhibition of the mitogen-activated protein kinase kinase-1 and -2 (MEK-1 and -2) downstream of RAF (rapidly accelerated fibrosarcoma) could sensitize RAI refractivity in thyroid cancer. However, a significant hurdle is the development of secondary tumor resistance (escape mechanisms) to these drugs through upregulation of tyrosine kinase receptors or another alternative signaling pathway. The sodium iodide symporter (NIS) is a plasma membrane glycoprotein, a member of solute carrier family 5A (SLC5A5), located on the basolateral surfaces of the thyroid follicular epithelial cells, which mediates active iodide transport into thyroid follicular cells. The mechanisms responsible for NIS loss of function in RAI-R thyroid cancer remains unclear. In a study of patients with recurrent thyroid cancer, expression levels of specific ribosomal machinery-namely PIGU (phosphatidylinositol glycan anchor biosynthesis class U), a subunit of the GPI (glycosylphosphatidylinositol transamidase complex-correlated with RAI avidity in radioiodine scanning, NIS levels, and biochemical response to RAI treatment. Here, we review the proposed mechanisms for RAI refractivity and the management of RAI-refractive metastatic, recurrent thyroid cancer. We also describe novel targeted systemic agents that are in use or under investigation for RAI-refractory disease, their mechanisms of action, and their adverse events.

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Molecular Basis of Cancer Pain Management: An Updated Review.

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Molecular Basis of Cancer Pain Management: An Updated Review.

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