Cancer pain: Journals & articles

Abstract
The aim of this qualitative study was to characterize opioid stigma in cancer remission using the Opioid Stigma Framework as a grounding theoretical framework. We conducted in-depth qualitative interviews with cancer survivors in remission who are currently or were previously prescribed opioids for moderate-to-severe pain related to their cancer diagnosis (n=17) and clinicians who routinely treat chronic cancer-related pain (n=20). Interviews occurred at a single institution from 05/2021-12/2021. The primary focus of this analysis was to describe perceived stigma from a patient perspective, as relayed by either survivors or treating clinicians. Survivors and clinicians perceived externalized stigma in a variety of healthcare settings, sometimes influenced by survivors' sociodemographic characteristics (e.g., race). Survivors and clinicians also reported stigmatizing behaviors from a variety of personal relationships, including family and community members, which then impacted decisions around prescription opioid use. Finally, survivors and clinicians described a pervasive sense of internalized stigma related to prescription opioid use in survivorship, including shame, embarrassment, and fear of addiction. Survivors and clinicians also reflected on known disparities in pain management, which in turn may have influenced experiences with opioid stigma. This research extends the Opioid Stigma Framework's concepts - previously described in patients with active cancer - to opioid stigma in cancer survivors. Given the frequency of opioid prescribing across the cancer continuum, it is crucial to develop targeted and tailored interventions to de-stigmatize clinical care and improve safe, effective chronic cancer pain management. PERSPECTIVE: Cancer survivors endorsed experiences with opioid stigma, including stigmatizing experiences with healthcare systems and personal relationships alongside negative internalized attitudes. Since opioid prescribing is common across the cancer continuum and into survivorship, it is necessary to develop tailored interventions to provide safe, effective, and de-stigmatized care to patients.

Abstract
Background: Opioids in step III of the WHO analgesic ladder are the standard of care for treating cancer pain. However, a significant minority of patients do not benefit from therapy. Genetics might play a role in predisposing patients to a good or poor response to opioids. Here, we investigated this issue by conducting a genome-wide association study (GWAS).

Methods: We genotyped 2057 European advanced cancer patients treated with morphine, buprenorphine, fentanyl and oxycodone. We carried out a whole-genome regression model (using REGENIE software) between genotypes and the opioid response phenotype, defined as a numerical score measuring patient pain intensity.

Results: The GWAS identified five non-coding variants on chromosome 20 with a p-value <5.0 × 10-8. For all of them, the minor allele was associated with lower pain intensity. These variants were intronic to the PCMTD2 gene and were 200 kbp downstream of OPRL1, the opioid related nociceptin receptor 1. Notably according to the eQTLGen database, these variants act as expression quantitative trait loci, modulating the expression mainly of PCMTD2 but also of OPRL1. Variants in the same chromosomal region were recently reported to be significantly associated with pain intensity in a GWAS conducted in subjects with different chronic pain conditions.

Conclusions: Our results support the role of genetics in the opioid response in advanced cancer patients. Further functional analyses are needed to understand the biological mechanism underlying the observed association and lead to the development of individualized pain treatment plans, ultimately improving the quality of life for cancer patients.

Significance statement: This genome-wide association study on European advanced cancer patients treated with opioids identifies novel regulatory variants on chromosome 20 (near PCMTD2 and OPRL1 genes) associated with pain intensity. These findings enhance our understanding of the genetic basis of opioid response, suggesting new potential markers for opioid efficacy. The study is a significant advancement in pharmacogenomics, providing a robust dataset and new insights into the genetic factors influencing pain intensity, which could lead to personalized cancer pain management.

Abstract
In September 2023, the Japanese Society for Palliative Medicine (JSPM) issued this consensus statement on chronic pain treatment in cancer survivors. With recent advances in the early diagnosis and treatment of cancer, its prognosis has improved, so prolonged pain in cancer survivors is considered to represent chronic pain and should be addressed. In this statement, we emphasize that not all cancer survivor pain is cancer pain. Pain that is not cancer pain should be managed with analgesics other than opioids and nerve blocks, and pain that persists despite this approach should be treated as non-cancer chronic pain so as to prevent opioid overuse. In addition, cancer survivors at any stage of disease have a potentially life-threatening condition and constantly carry the fear of cancer recurrence. Therefore, even non-cancer pain should not be treated in the same way as general chronic pain, but should be managed with consideration of emotional distress. In the future, we plan to create educational tools for healthcare professionals and to conduct online seminars, both with the goal of providing cancer survivors with appropriate assessment and treatment of chronic pain.

Abstract
Objectives: Cancer pain is among the most prevalent and challenging symptoms in cancer care, with up to 95% of patients with late-stage cancer experiencing moderate-to-severe pain. Conventional pharmacologic treatments, including opioids, carry risks, and patients' conditions may be refractory to medical management or have contraindications. Neurostimulation techniques, such as spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRGS), and peripheral nerve stimulation (PNS), have shown promise in treating treatment-induced cancer pain. However, a comprehensive review focusing on these techniques for cancer-induced pain alone is necessary.

Materials and methods: A comprehensive literature review was conducted using Medline, Embase, and Cochrane Library data bases, focusing on studies from 2000 onward. Inclusion criteria included interventional and observational studies reporting on SCS, DRGS, and PNS in cancer-induced pain. Studies addressing treatment-induced pain, systematic reviews, meta-analyses, and non-English studies were excluded. Data were extracted and evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation system.

Results: The search yielded 831 references, with 24 studies meeting the inclusion criteria. Sixteen studies focused on SCS, seven on PNS, and two cases on DRGS. SCS showed significant pain reduction, with an average decrease in numeric rating scale (NRS) scores from 8.0 to 2.2 over an average 8.4-month follow-up period. PNS also indicated substantial pain relief, with NRS scores decreasing from 8.29 to 3.04 over an average 5.2-month follow-up period. DRGS, although less studied, showed a reduction in NRS scores from 6.0 to 1.0 over an average 6.0-month follow-up period. SCS was associated with a significant reduction in opioid use, with average reported morphine equivalent daily dose (MEDD) change from 1152.2 mg to 739.7 mg over an average 5.0-month period, whereas PNS and DRGS had limited impact on opioid consumption, with no reported MEDD change.

Conclusions: Our scoping review synthesizes evidence on neurostimulation interventions for treating cancer-induced pain. Current evidence suggests that interventions such as SCS, DRGS, and PNS may provide clinically meaningful pain relief in patients with cancer-induced pain. Several studies also reported improvements in functionality and quality of life. However, the level of evidence is limited owing to the lack of prospective comparative studies, clinical and methodologic heterogeneity, and small sample sizes.

Abstract
Background: Effective management of cancer pain critically depends on timely medication administration and adherence to precise medication guidelines. In the context of limited time and a busy healthcare environment, tailoring the optimal medication schedule for each patient with cancer pain presents a significant challenge for physicians and clinical pharmacists.

Methods: To address this challenge, we conducted a comprehensive analysis of healthcare professionals' needs in guiding cancer pain medication. By developing core features based on key user needs and continuously updating them, we have created the Universal Medication Schedule System (UMSS). We invited 20 physicians and pharmacists specializing in oncology or cancer pain to trial the system and assessed UMSS usage through distributed questionnaires.

Results: We identified five key needs of healthcare professionals in cancer pain medication guidance. Based on these needs, we (1) constructed a comprehensive drug information database, including basic information for 1135 drugs, 130,590 drug interaction data entries, and 1409 individual medication timing constraints, and (2) developed a web-based system that provides essential reference information such as drug interactions and dietary restrictions. It can create medication schedules and provide medication education tailored to the patient's daily routine. Participating evaluators unanimously agreed (100%) that the system aids in accurately assessing the risks of polypharmacy and quickly scheduling medication regimens.

Conclusion: UMSS, by offering personalized medication schedule support, assists healthcare professionals in better managing patients' medication treatment plans. However, further improvements are needed in the automation of database updates and maintenance, as well as in integrating it with electronic health records.

Abstract
Background: Tailoring effective strategies for cancer pain management requires a careful analysis of multiple factors that influence pain phenomena and, ultimately, guide the therapy. While there is a wealth of research on automatic pain assessment (APA), its integration with clinical data remains inadequately explored. This study aimed to address the potential correlations between subjective and APA-derived objectives variables in a cohort of cancer patients.

Methods: A multidimensional statistical approach was employed. Demographic, clinical, and pain-related variables were examined. Objective measures included electrodermal activity (EDA) and electrocardiogram (ECG) signals. Sensitivity analysis, multiple factorial analysis (MFA), hierarchical clustering on principal components (HCPC), and multivariable regression were used for data analysis.

Results: The study analyzed data from 64 cancer patients. MFA revealed correlations between pain intensity, type, Eastern Cooperative Oncology Group Performance status (ECOG), opioids, and metastases. Clustering identified three distinct patient groups based on pain characteristics, treatments, and ECOG. Multivariable regression analysis showed associations between pain intensity, ECOG, type of breakthrough cancer pain, and opioid dosages. The analyses failed to find a correlation between subjective and objective pain variables.

Conclusions: The reported pain perception is unrelated to the objective variables of APA. An in-depth investigation of APA is required to understand the variables to be studied, the operational modalities, and above all, strategies for appropriate integration with data obtained from self-reporting.

Trial registration: This study is registered with ClinicalTrials.gov, number (NCT04726228), registered 27 January 2021, https://classic.

Clinicaltrials: gov/ct2/show/NCT04726228?term=nct04726228&draw=2&rank=1.

Abstract
Neuropathic cancer pain is experienced by 30-40% of patients with cancer. It significantly reduces quality of life and overall wellbeing for patients living with and beyond cancer. The underlying mechanisms of neuropathic pain in patients with cancer are complex and involve direct tumour involvement, nerve compression or infiltration, chemotherapy and/or radiotherapy-induced nerve damage, or post-surgical complications. It is crucial for healthcare professionals to assess and manage neuropathic cancer pain effectively. There is increasing recognition that standardisation of neuropathic pain assessment leads to tailored management and improved patient outcomes. Pain management strategies, including medication, interventional analgesia, physical and complementary therapy, can help alleviate neuropathic pain and improve the patient's comfort and quality of life.

Abstract
Background: The Stop Cancer PAIN Trial was a phase III pragmatic stepped wedge cluster randomised controlled trial which compared effectiveness of screening and guidelines with or without implementation strategies for improving pain in adults with cancer attending six Australian outpatient comprehensive cancer centres (n = 688). A system for pain screening was introduced before observation of a 'control' phase. Implementation strategies introduced in the 'intervention' phase included: (1) audit of adherence to guideline recommendations, with feedback to clinical teams; (2) health professional education via an email-administered 'spaced education' module; and (3) a patient education booklet and self-management resource. Selection of strategies was informed by the Capability, Opportunity and Motivation Behaviour (COM-B) Model (Michie et al., 2011) and evidence for each strategy's stand-alone effectiveness. A consultant physician at each centre supported the intervention as a 'clinical champion'. However, fidelity to the intervention was limited, and the Trial did not demonstrate effectiveness. This paper reports a sub-study of the Trial which aimed to identify factors inhibiting or enabling fidelity to inform future guideline implementation initiatives.

Methods: The qualitative sub-study enabled in-depth exploration of factors from the perspectives of personnel at each centre. Clinical champions, clinicians and clinic receptionists were invited to participate in semi-structured interviews. Analysis used a framework method and a largely deductive approach based on the COM-B Model.

Results: Twenty-four people participated, including 15 physicians, 8 nurses and 1 clinic receptionist. Coding against the COM-B Model identified 'capability' to be the most influential component, with 'opportunity' and 'motivation' playing largely subsidiary roles. Findings suggest that fidelity could have been improved by: considering the readiness for change of each clinical setting; better articulating the intervention's value proposition; defining clinician roles and responsibilities, addressing perceptions that pain care falls beyond oncology clinicians' scopes of practice; integrating the intervention within existing systems and processes; promoting patient-clinician partnerships; investing in clinical champions among senior nursing and junior medical personnel, supported by medical leaders; and planning for slow incremental change rather than rapid uptake.

Conclusions: Future guideline implementation interventions may require a 'meta-implementation' approach based on complex systems theory to successfully integrate multiple strategies.

Abstract
Background: Breast cancer is the most frequent type of cancer and the second leading cause of cancer-related mortality in women. Mastectomies remain a key component of the treatment of non-metastatic breast cancer, and strategies to treat acute postoperative pain, a complication affecting nearly all patients undergoing surgery, continues to be an important clinical challenge. This study aimed to determine the impact of intraoperative methadone administration compared to conventional short-acting opioids on pain-related perioperative outcomes in women undergoing a mastectomy.

Methods: This single-center retrospective study included adult women undergoing total mastectomy. The primary outcome of this study was postoperative pain intensity on day 1 after surgery. Secondary outcomes included perioperative opioid consumption, perioperative non-opioid analgesics use, duration of surgery and anesthesia, time to extubation, pain intensity in the postanesthesia care unit (PACU), anti-emetic use in PACU, and length of stay in hospital. We used the propensity score-based nearest matching with a 1:3 ratio to balance the patient baseline characteristics.

Results: 133 patients received methadone, and 2192 patients were treated with short-acting opioids. The analysis demonstrated that methadone was associated with significantly lower intraoperative and postoperative opioid consumption as measured by oral morphine equivalents and lower average pain intensity scores in the postanesthesia care unit. Moreover, methadone was also shown to reduce the use of non-opioid analgesia during surgery.

Conclusion: Our study suggests that the unique pharmacological properties of methadone, including a short onset of action when given intravenously, long-acting pharmacokinetics, and multimodal effects, are associated with better acute pain management after a total mastectomy.

Abstract
Purpose: Cancer patients often experience pain, which can greatly reduce their quality of life. It affects their emotions, cognitive function, and daily interactions. Healthcare providers need to understand the obstacles to pain management to create helpful programs for patients and families. This study focuses on Iranian nurses' views on pain management barriers in cancer patients.

Methods: The study utilized a qualitative content analysis method with a purposive sampling approach, involving 27 nurses. Participants were selected to ensure a wide range of perspectives and experiences by considering factors such as gender, age, work experience, education levels, and positions until data saturation was achieved. Inclusion criteria specified a minimum of six months of oncology ward experience and a bachelor's degree or higher in nursing. Nurses with less than six months of oncology experience or lacking a nursing degree were excluded. Data collection was conducted through semi-structured interviews and analyzed using Lundman and Granheim's qualitative content analysis method.

Results: One main theme, four main categories, and nine subcategories in the study reflected the nurses' experiences and viewpoints about barriers to pain management. These categories included the marginalization of complementary medicine, medical malpractice, inadequate organizational infrastructure, and personal barriers.

Conclusion: The study demonstrated that the barriers to pain management in cancer patients were complex. To improve patients' comfort and quality of life, it is important to identify and address issues from different angles. It is crucial to train patients and healthcare providers in pain management and to address weaknesses in the healthcare system.

Abstract
The management and treatment of bone cancer pain (BCP) remain significant clinical challenges, imposing substantial economic burdens on patients and society. Extensive research has demonstrated that BCP induces changes in the gene expression of peripheral sensory nerves and neurons, which play crucial roles in the onset and maintenance of BCP. However, our understanding of the epigenetic mechanisms of BCP underlying the transcriptional regulation of pro-nociceptive (such as inflammatory factors and the transient receptor potential family) and anti-nociceptive (such as potassium channels and opioid receptors) genes remains limited. This article reviews the epigenetic regulatory mechanisms in BCP, analyzing the roles of histone modifications, DNA methylation, and noncoding RNAs (ncRNAs) in the expression of pro-nociceptive and anti-nociceptive genes. Finally, we provide a comprehensive view of the functional mechanisms of epigenetic regulation in BCP and explore the potential of these epigenetic molecules as therapeutic targets for BCP.

Abstract
Background: Chemotherapy-induced peripheral neuropathy (CIPN) following oral or intravenous chemotherapy often results in neuropathic pain, accompanied by symptoms such tingling, burning and hypersensitivity to stimuli, with a notable decline in quality of life (QoL). Effective therapies for CIPN are lacking, with a high demand for analgesics to address this issue. The QUCIP study aimed to assess the effectiveness of high concentration (179 mg) capsaicin patch (HCCP) in alleviating neuropathic pain and associated symptoms in breast cancer patients with confirmed CIPN.

Methods: QUCIP is a prospective, multi-center observational study spanning 36 weeks with up to three HCCP treatments. Initial treatment (visit V0) was followed by two telephone contacts (T1, T2) and subsequent face-to-face visits every 12 weeks or upon retreatment (visits V1-V3). 73 female patients with painful CIPN post neoadjuvant/adjuvant breast cancer therapy were enrolled. Primary endpoint was the reduction of neuropathic pain symptom score (painDETECT®). Secondary endpoints included improvements in CIPN-specific QoL (QLQ-CIPN20), reductions in pain intensity (numeric pain rating scale, NPRS), and achievement of ≥ 30% and ≥ 50% pain reduction.

Results: Median age was 61 years, with 52.0% of patients experiencing peripheral neuropathic pain for > 1 year (> 2 years: 34.2%). The painDETECT® score significantly decreased from baseline (19.71 ± 4.69) to 15.80 ± 6.20 after initial treatment (p < 0.0001) and continued to decrease at follow-up visits. The NPRS indicated significant pain intensity reduction at each time point, particularly pronounced in patients receiving three HCCP treatments. Clinically significant pain relief of ≥ 30% increased from 25.0% at week 4 (T2) to 36.2%, 43.5%, and 40.0% at weeks 12 (V1), 24 (V2), and 36 (V3), respectively. The percentage of patients achieving pain relief of ≥ 50% increased from 14.7% at T2 to 15.5%, 21.7% and 32.5% at V1, V2 and V3, respectively. Patients further reported a significant improvement in their CIPN-related QoL throughout the study. Adverse drug reactions (ADRs) mainly included application site reactions.

Conclusion: In this study, HCCP shows benefit in managing CIPN in real-world settings. The data demonstrate a sustained and progressive reduction in neuropathic pain and symptomatology, confirming the clinical benefit of repeated treatment observed in former clinical trials. HCCP treatment has also the potential to significantly improve the QoL associated with CIPN. The safety profile of HCCP was confirmed, supporting its use in clinical practice.

Abstract
People with a substance use disorder (SUD) have shortened lifespans due to complications from their substance use and challenges engaging with traditional health care settings and institutions. This impact on life expectancy is especially prominent in patients with co-occurring SUDs and cancer, and often has a much worse prognosis from the cancer than a similar patient without a SUD. Palliative care teams are experts in serious illness communication and symptom management and have become increasingly embedded in the routine care of patients with cancer. We argue that the skill set of palliative care teams is uniquely suited for addressing the needs of this oft marginalized group. We provide a comprehensive review of tools for addressing these needs, including medications that can both treat pain and opioid use disorder (OUD), and highlight psychosocial approaches to treating patients with OUD and cancer in a way that is respectful and effective. Using a trauma informed framework, we focus on the application of harm reduction principles from addiction medicine and the principles of clear communication, accompaniment, and emotional presence from palliative care to maximize support. We also focus on ways to reduce stigma in the delivery of care, by providing language that reduces barriers and increases patient engagement. Finally, we describe a clinic embedded within our institution's cancer center which aims to serve patients with cancer and SUDs, built on the framework of harm reduction, accompaniment and trauma informed care (TIC). Overall, we aim to provide context for addressing the common challenges that arise with patients with cancer and OUD, including the direct impact of psychosocial stress on substance use and cancer treatment, delays in disease directed treatment that can potentially impact further treatment options and outcomes, challenging pain management due to greater opioid debt, and potential loss of primary coping mechanism through substance use in the face of potential terminal diagnosis.

Abstract
Background: Cancer pain remains highly prevalent and persistent throughout survivorship, and it is crucial to investigate the potential of leveraging the advanced features of mobile health (mHealth) apps to empower individuals to self-manage their pain.

Objective: This review aims to comprehensively understand the acceptability, users' experiences, and effectiveness of mHealth apps in supporting cancer pain self-management.

Methods: We conducted an integrative review following Souza and Whittemore and Knafl's 6 review processes. Literature was searched in PubMed, Scopus, CINAHL Plus with Full Text, PsycINFO, and Embase, from 2013 to 2023. Keywords including "cancer patients," "pain," "self-management," "mHealth applications," and relevant synonyms were used in the search. The Johns Hopkins research evidence appraisal tool was used to evaluate the quality of eligible studies. A narrative synthesis was conducted to analyze the extracted data.

Results: A total of 20 studies were included, with the overall quality rated as high (n=15) to good (n=5). Using mHealth apps to monitor and manage pain was acceptable for most patients with cancer. The internal consistency of the mHealth in measuring pain was 0.96. The reported daily assessment or engagement rate ranged from 61.9% to 76.8%. All mHealth apps were designed for multimodal interventions. Participants generally had positive experiences using pain apps, rating them as enjoyable and user-friendly. In addition, 6 studies reported significant improvements in health outcomes, including enhancement in pain remission (severity and intensity), medication adherence, and a reduced frequency of breakthrough pain. The most frequently highlighted roles of mHealth apps included pain monitoring, tracking, reminders, education facilitation, and support coordination.

Conclusions: mHealth apps are effective and acceptable in supporting pain self-management. They offer a promising multi-model approach for patients to monitor, track, and manage their pain. These findings provide evidence-based insights for leveraging mHealth apps to support cancer pain self-management. More high-quality studies are needed to examine the effectiveness of digital technology-based interventions for cancer pain self-management and to identify the facilitators and barriers to their implementation in real-world practice.

Abstract
Opioid therapy is the mainstay for managing pain in pediatric oncology. This narrative review describes the current literature regarding opioids for pediatric cancer pain. The review explores the multifaceted landscape of opioid utilization in this population, including the role of opioids in certain clinical circumstances, modalities of opioid delivery, unique opioids, outpatient and at-home pain management strategies, and other key concepts such as breakthrough pain. This review highlights the importance of individualized dosing and multimodal approaches to enhance efficacy and minimize adverse effects. Drawing from a wide range of evidence, this review offers insights to optimize pediatric oncology pain management.

Abstract
The epidemiology and prognosis of radiation-induced chronic pain, especially chronic neuropathic pain (CNP), are the understudied domain among head and neck cancer (HNC) survivors after radiotherapy (RT). This study aimed to estimate the prevalence of such chronic pain, and explore their correlations with mental health, sleep disorders, cognitive function, and quality of life (QOL) within these patients. This research encompassed HNC survivors post-RT. The determination of radiation-induced chronic pain and CNP adhered to the guidelines outlined by the International Association for the Study of Pain (IASP). Multivariable regression analyses were employed to explore the relationship between pain and anxiety, depression, sleep disturbances, cognitive function, and QOL. A total of 1071 HNC survivors post-RT were included in this study. The prevalence of radiation-induced chronic pain was 67.1%, and the prevalence of RT-associated CNP was 38.3%,. Compared with those reporting no pain, patients with radiation-induced chronic pain had a significantly increased risk of anxiety, depression and sleep disorders (all p < 0.001). And there was a significantly negative association between chronic pain and QOL across physiological (p < 0.001), psychological (p < 0.001), social relationships (p = 0.001) and environmental (p = 0.009) domains. Compared with non-CNP, patients with RT-related CNP had a higher risk of anxiety (p= 0.027) and sleep disorders (p= 0.013). The significantly negative associations were found between CNP and the physiological (p = 0.001), psychological (p = 0.012) and social score (p = 0.035) in WHOQOL-BREF. This study underscores the substantial prevalence of chronic pain, particularly CNP, and their potential impact on the mental health, sleep, and QOL among HNC survivors post-RT. PERSPECTIVE: This study highlights the high prevalence of radiation-induced chronic pain and CNP, and their potential impacts on anxiety, depression, sleep and QOL among the HNC survivors. Clinically, these findings have important implications for improving the care and outcomes of HNC survivors.

Abstract
Chronic pain often coincides with changes in gut microbiota composition. Yet, the role of gut microbiota in bone cancer pain(BCP) is still not fully understood. This study investigated the role of gut microbiota in BCP and the effect of oxymatrine(OMT) on gut microbiota in BCP. A BCP mice model was developed to assess gut microbiota composition, serum and brain tissue butyric acid levels, and blood-brain barrier(BBB) permeability. Microbiota transplantation was used to restore gut microbiota, and the effect of Clostridium butyricum (C. butyricum) or sodium butyrate(NaB) supplementation on pain-related behaviors and BBB integrity was evaluated. The potential benefits of OMT on gut microbiota composition, PPARγ/COX-2 signaling, BBB integrity, and pain-related behaviors were also explored. BCP significantly altered gut microbiota composition and reduced serum and brain tissue butyric acid levels. Additionally, BBB permeability increased considerably in the BCP group compared to sham and control mice. Microbiota transplantation, as well as C. butyricum or NaB supplementation, ameliorated pain-related behaviors and BBB integrity; the supplementation of C. butyricum or NaB boosted brain tight junction protein expression, potentially through modulating PPARγ/COX-2 signaling. OMT influenced gut microbiota composition and regulated PPARγ/COX-2 signaling in the BCP model, improving pain-related behaviors and BBB integrity. BCP affects gut microbiota composition and butyric acid levels. Modulating gut microbiota and butyric acid levels through transplantation or supplementation may alleviate BCP. OMT shows potential as a treatment by altering gut microbiota composition and regulating PPARγ/COX-2 signaling. These findings provide new insights into BCP pathophysiology and possible treatments. PERSPECTIVE: This study explores the impact of gut microbiota on bone cancer pain (BCP). Microbiota transplantation alleviates BCP and enhances BBB integrity. Also, Clostridium butyricum or sodium butyrate improves BBB via PPARγ/COX-2. Oxymatrine (OMT), a BCP treatment, modifies microbiota by regulating PPARγ/COX-2, in turn improving pain and BBB integrity. These findings suggest a therapeutic approach, emphasizing clinical relevance in targeting gut microbiota and restoring butyric acid levels.

Abstract
Background: The present study sought to determine the prevalence of chronic non-cancer pain (CNCP) among older adult inpatients with polypharmacy. It also aimed to analyse prescription patterns and assess the therapy adequacy and patient complexity for those with and without CNCP.

Methods: This 4-year longitudinal study examined data from an exhaustive acute care hospital register on home-dwelling older adult patients (≥65) with polypharmacy. Commonly known combinations of potentially inappropriate medications were used to estimate therapy adequacy. Patient complexity was evaluated by comparing number of comorbidities and investigating physical and cognitive deficits.

Results: We determined a prevalence of CNCP of 9.7% among all older adult inpatients with polypharmacy, rising to 11.3% for those aged ≥85. Overall, CNCP patients were prescribed more drugs and had more comorbidities and physical and cognitive deficits than patients without CNCP. Older adult patients with CNCP received more analgesics, greater quantities of opioids, paracetamol and co-analgesics and elevated opioid dosages. Older adult patients with CNCP aged ≥85 received fewer analgesics, opioids, non-steroidal anti-inflammatory drugs and co-analgesics but more paracetamol. Older adult patients with CNCP were prescribed more potentially inappropriate medications involving opioids. In particular, 24.5% received an opioid and a hypnotic (benzodiazepine or Z-drug), and 8.6% received an opioid and a gabapentinoid.

Conclusion: Observed differences in medication use between older adult inpatients with or without CNCP may be relevant for clinical practice. Potentially inadequate co-prescribing (such as hypnotics and opioids) affects a higher proportion of patients with CNCP and may have serious unintended consequences.

Significance statement: This study describes differences in prescription patterns between people with and without chronic non-cancer pain in a large dataset of 20,422 discharges. The differences found may be relevant to clinical practice. In particular, high co-prescribing of opioids and hypnotics may have serious unintended consequences. Greater physical and cognitive deficits may indicate greater patient complexity, and appropriate interventions need to be developed to improve the management of this vulnerable patient group.

Abstract
This study examined the effects of intrathecal analgesia (ITA) using an extracorporeal pump with a subcutaneous port system in cancer patients with bone metastasis. Among the patients who died of cancer with bone metastasis at the palliative care unit of our institution, 11 who received ITA were selected. Changes in pain, opioid doses, the palliative prognostic index (PPI), and Eastern Cooperative Oncology Group Performance Scale after ITA were assessed. Pain, opioid doses, and PPI decreased after ITA (P = 0.002, 0.002, and 0.017). ITA for cancer patients with increased PPI due to refractory cancer bone pain decreased pain, opioid doses, and PPI.(100 words).

Abstract
Background: Persistent postsurgical pain (PPSP) after lung cancer surgery is common and current definitions are based on evaluations at a single time point after surgery. Pain intensity and symptoms may however fluctuate and change over time, and be impacted by multiple and shifting factors. Studies of postoperative recovery patterns and transition from acute to chronic pain are needed for further investigation of preventive measures and treatments to modify unfavourable recovery paths.

Methods: In this explorative study, 85 patients undergoing surgery due to either presumptive or confirmed lung cancer reported pain intensities bi-monthly for 12 months. Pain trajectories during recovery were investigated, using group-based trajectory modelling. Associations with possible risk factors for PPSP, including clinical variables and anxiety and depression score (HADS), were also explored.

Results: A trajectory model containing three 12-month pain recovery groups was computed. One group without PPSP fully recovered (50%) within two to three months. Another group with mild-intensity PPSP followed a protracted recovery trajectory (37%), while incomplete recovery was observed in the last group (13%). Acute postoperative pain and younger age were associated with a less favourable recovery trajectory. More neuropathic pain symptoms were observed in patients with incomplete recovery.

Conclusions: Three clinically relevant recovery trajectories were identified, based on comprehensive pain tracking. Higher acute postoperative pain intensity was associated with an unfavourable pain recovery trajectory.

Significance statement: Understanding the transition from acute to chronic postoperative pain and identifying preoperative risk factors is essential for the development of targeted treatments and the implementation of preventive measures. This study (1) identified distinct recovery trajectories based on frequent pain assessment follow-ups for 12 months after surgery and (2) evaluated risk factors for unfavourable postoperative pain recovery paths. Findings suggest that early higher postoperative pain intensity is associated with an unfavourable long-term recovery path.

Abstract
Neuropathic cancer pain (NCP) is prevalent affecting up to 58% of those with persistent pain following cancer treatment. Neuropathic pain can develop from malignancy, after neural tissue insult during surgery and/or exposure to radiation or neurotoxic agents used as part of cancer treatment regimens. Pain following cancer treatment is commonly under-treated and one barrier identified is poor recognition of pain and inadequate assessment. Recognition of the presence of NCP is important to inform pain management, which is challenging to treat and warrants the use of specific treatments to target neuropathic mechanisms. In this review, approaches for screening and classifying NCP are described. These include screening questionnaires and the application of the updated neuropathic pain grading system in a cancer context. The evidence from neuropathic pain related assessments in cancer populations is provided and highlighted under different neuropathic pain grades. Recommendations for assessment in practice are provided.

Abstract
Background/objective Pain is a challenging multifaceted symptom reported by most cancer patients, resulting in a substantial burden on both patients and healthcare systems. This systematic review aims to explore applications of artificial intelligence/machine learning (AI/ML) in predicting pain-related outcomes and supporting decision-making processes in pain management in cancer.

Methods A comprehensive search of Ovid MEDLINE, EMBASE and Web of Science databases was conducted using terms including “Cancer”, “Pain”, “Pain Management”, “Analgesics”, “Opioids”, “Artificial Intelligence”, “Machine Learning”, “Deep Learning”, and “Neural Networks” published up to September 7, 2023. The screening process was performed using the Covidence screening tool. Only original studies conducted in human cohorts were included. AI/ML models, their validation and performance and adherence to TRIPOD guidelines were summarized from the final included studies.

Results This systematic review included 44 studies from 2006-2023. Most studies were prospective and uni-institutional. There was an increase in the trend of AI/ML studies in cancer pain in the last 4 years. Nineteen studies used AI/ML for classifying cancer patients’ pain development after cancer therapy, with median AUC 0.80 (range 0.76-0.94). Eighteen studies focused on cancer pain research with median AUC 0.86 (range 0.50-0.99), and 7 focused on applying AI/ML for cancer pain management decisions with median AUC 0.71 (range 0.47-0.89). Multiple ML models were investigated with. median AUC across all models in all studies (0.77). Random forest models demonstrated the highest performance (median AUC 0.81), lasso models had the highest median sensitivity (1), while Support Vector Machine had the highest median specificity (0.74). Overall adherence of included studies to TRIPOD guidelines was 70.7%. Lack of external validation (14%) and clinical application (23%) of most included studies was detected. Reporting of model calibration was also missing in the majority of studies (5%).

Conclusion Implementation of various novel AI/ML tools promises significant advances in the classification, risk stratification, and management decisions for cancer pain. These advanced tools will integrate big health-related data for personalized pain management in cancer patients. Further research focusing on model calibration and rigorous external clinical validation in real healthcare settings is imperative for ensuring its practical and reliable application in clinical practice.

Abstract
Background: Opioid dose titration is a fundamental process of opioid therapy in cancer pain.

Aims: To assess data opioid dose titration.

Methods: The principal opioid dose titration methods, outcomes, and modalities of administration regarding the different opioid preparations were examined in different clinical contexts.

Results: Most studies suggested that opioid-naive patients should be started at doses of 15-30 mg/day of oral morphine equivalents. Opioid-tolerant patients may receive low or higher doses of oral morphine equivalents, depending on the level of opioid tolerance. Generally, dose increments of 30%-50% seem to be indicated to start dose titration. Some patients with severe excruciating cancer pain may present as an emergency requiring a rapid application of powerful analgesic strategies. The intravenous use of opioids may circumvent this problem providing a faster pain relief, due to the large availability and rapid achievement of effective plasma concentrations.

Discussion: Opioid dose titration is a delicate passage in patients with cancer pain. This approach may be different according to different clinical conditions. Opioid dose titration requires expertise to optimize cancer pain management while minimizing the development of adverse effects.

Conclusion: While most approaches are meaningful and partially supported by existing literature, more studies are necessary to establish advantages and disadvantages in different clinical conditions. Optimization of opioid dose titration is of paramount importance.

Significance: This review provides the most recent insights on the different modalities of opioid dose titration in cancer pain management.

Abstract
Background: Pain is a common side effect of cancer or cancer treatment that negatively impacts biopsychosocial wellbeing and quality of life. Exercise is a potential intervention to manage pain that is safe and has multiple benefits. The objective was to determine the role of exercise in cancer pain management.

Methods: We completed a systematic review and meta-analysis of exercise interventions in adults with any type or stage of cancer by searching Ovid MEDLINE®, Embase, APA PsycInfo, the Cochrane Central Register of Controlled Trials, CINAHL, and SPORTDiscus. We included experimental and quasi-experimental designs where pain was measured as an outcome. Data synthesis included narrative and tabular summary. A meta-analysis was performed on studies powered to detect the effect of exercise on pain. Study quality was evaluated using the Cochrane risk of bias tool and certainty of evidence was evaluated using the GRADE tool.

Results: Seventy-six studies were included. Studies were predominantly conducted in breast cancer and exercise usually included a combination of aerobic and strength training. Ten studies were included in the meta-analysis demonstrating a significant effect for exercise in decreasing pain (estimated average standard mean difference (SMD) was g = - 0.73 (95% CI: - 1.16 to - 0.30)); however, the overall effect prediction interval was large. Overall risk of bias for most studies was rated as some concerns and the grading of evidence certainty was low.

Conclusion: There are limitations in the evidence for exercise to manage cancer-related pain. Further research is needed to understand the role of exercise in a multimodal pain management strategy.

Abstract
Purpose of review: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and often painful condition that occurs after administration of chemotherapeutic agents. The primary objective of this systematic review was to appraise the literature on conservative, pharmacological, and interventional treatment options for CIPN pain.

Recent findings: There is level I evidence supporting modest to moderate improvement in CIPN pain from duloxetine treatment, as well as short-term modest improvement from physical therapy and acupuncture. Although opioid and cannabis administration may provide short-term modest improvement, administration is commonly limited by side effects. Generally, most studies reported no clinical benefit from yoga, topical neuropathic agents, gabapentinoids, and tricyclic antidepressants. Evidence is currently equivocal for scrambler therapy and transcutaneous electrical nerve stimulation. Finally, evidence on neuromodulation options is limited to mostly case reports/series and one observational study highlighting moderate improvement with auricular nerve stimulation. This systematic review provides an overview of conservative, pharmacologic, and interventional treatment modalities for CIPN pain. Furthermore, it provides a level of evidence and degree of recommendation based on the United States Preventive Services Task Force (USPSTF) criteria for each specific treatment modality.

Abstract
The management of pain for patients with cancer and cancer survivors is a critical clinical task that involves a multitude of ethical issues at almost every phase of the cancer experience. This review is divided into three sections: In the first, we address rights and duties in the relief of pain from the perspective of patients, clinicians, health care institutions and organizations, and public policy. This section includes a detailed description of issues and duties in relation to opioid misuse and addiction. In the second section, we discuss the ethical consideration of therapeutic planning. The final section addresses ethical considerations in the management of pain at the end of life including a detailed discussion regarding ethical issues relating to the use of palliative sedation as a clinical intervention of last resort.

Abstract
Purpose: The present investigation explores multi-agent systems, their function in cancer pain management, and how they might enhance patient care. Since cancer is a complex disease, technology can help doctors and patients coordinate care and communicate effectively. Even when a patient has a dedicated team, treatment may be fragmented. Multi-agent systems (MAS) are one component of technology that is making progress for cancer patients. Wireless sensory networks (WSN) and body area sensory networks (BASN) are examples of MAS.

Recent findings: Technology is advancing the care of patients, not only in everyday clinical practice, but also in creating accessible communication between patients and provider. Many hospitals have utilized electronic medical records (EHR), but recent advancements allowed the pre-existing infrastructure to network with personal devices creating a more congruent form of communications. Better communication can better organize pain management, leading to better clinical outcomes for patients, integrating body sensors, such as smart watch, or using self-reporting apps. Certain software applications are also used to help providers in early detections of some cancers, having accurate results. The integration of technology in the field of cancer management helps create an organized structure for cancer patients trying to understand/manage their complex diagnosis. The systems for the various healthcare entities can receive and access frequently updated information that can better provide better coverage of the patient's pain and still be within the legalities as it pertains to opioid medications. The systems include the EHR communicating with the information provided by the patient's cellular devices and then communicating with the healthcare team to determine the next step in management. This all happens automatically with much physical input from the patient decreasing the amount of effort from the patient and hopefully decreasing the number of patients' loss to follow-up.

Abstract
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.

Abstract
Introduction: Pain is one of the most persistent symptoms after cancer treatment. The central nervous system can erroneously stay in its alarm phase, altering the pain experience of patients who have cancer. Pain neuroscience education (PNE) with multimodal approaches may benefit these patients.

Objective: This protocol aims to determine the effectiveness of a PNE tool on pain, physical function and quality of life, as a supplement to a multimodal rehabilitation (MR) program in patients who had breast cancer (BC).

Methods: An 8-week double-blinded randomized controlled trial will be conducted, including 72 participants who had BC and who have persistent pain, randomized into three groups: PNE program + MR program, traditional biomedical information + MR program and control group. The PNE program will include educational content that participants will learn through a mobile app and the MR program will include a concurrent exercise program and manual therapy. The primary outcome will be the perceived pain assessed using the Visual Analogue Scale and secondary outcomes are others related to pain, physical function and quality of life. All outcomes will be evaluated at baseline, at the end of the intervention and 6 months after the end of intervention.

Discussion: The proposed study may help BC patients with persistent pain improve their pain experience, quality of life and provide for more adaptive pain-coping strategies. This protocol could propose an action guide to implement different integral approaches for the treatment of sequelae. This treatment option could be offered to this patient profile and it could be easily implemented in the healthcare systems due to its low costs.

Cancer Treatment and Research Communications is an international peer-reviewed publication dedicated to providing comprehensive basic, translational, and clinical oncology research. The journal is devoted to articles on detection, diagnosis, prevention, policy, and treatment of cancer and provides a global forum for the nurturing and development of future generations of oncology scientists.

A multi-disciplinary, international journal that aims to be a global forum on all aspects of pain research and pain management. The journal publishes clinical and basic science research papers relevant to all aspects of pain and its management.

The Journal of Opioid Management deals with all aspects of opioids. From basic science, pre-clinical, clinical, abuse, compliance and addiction medicine, the journal provides and unbiased forum for researchers and clinicians to explore and manage the complexities of opioid prescription.

This journal provides a forum for the publication of the latest clinical research and best practices related to the relief of illness burden among patients afflicted with serious or life-threatening illness.

Nature Cancer aims to provide a unique forum through which the cancer community will learn about the latest, most significant cancer-related advances across the life, physical, applied and social sciences. Areas of interest include fundamental, preclinical research that furthers our understanding of the mechanisms underlying tumour initiation, propagation and progression; work aiming to translate this knowledge to the clinic by focusing on new approaches for the development and delivery of diagnostic and therapeutic modalities; clinical studies informing cancer diagnosis, treatment and prevention; and new ways of understanding the global societal impact of cancer.

Nature Reviews Cancer aims to be the premier source of reviews and commentaries for the scientific communities we serve. We strive to publish articles that are authoritative, accessible and enhanced with clearly understandable figures, tables and other display items. We want to provide an unparalleled service to authors, referees and readers, and we work hard to maximize the usefulness and impact of each article. The journal publishes Research Highlights, Comments, Reviews and Perspectives relevant to cancer researchers, with our broad scope ensuring that the articles we publish reach the widest possible audience.

npj Breast Cancer publishes original research articles, reviews, brief communications, matters arising, meeting reports and hypothesis generating observations which could be unexplained or preliminary findings from experiments, novel ideas, or the framing of new questions that need to be solved. Featured topics of the journal include imaging, immunotherapy, molecular classification of disease, mechanism-based therapies largely targeting signal transduction pathways, carcinogenesis including hereditary susceptibility and molecular epidemiology, survivorship issues including long-term toxicities of treatment and secondary neoplasm occurrence, the biophysics of cancer, mechanisms of metastasis and their perturbation, and studies of the tumor microenvironment.

Pain Practice, the official journal of the World Institute of Pain, publishes international multidisciplinary articles on pain and analgesia that provide its readership with up-to-date research, evaluation methods, and techniques for pain management.

Pain Research and Management is a peer-reviewed, open access journal which publishes original research articles and review articles involving laboratory, including neuroimaging and neurophysiology, and clinical findings in the field of pain research. The journal also looks into the prevention, treatment and management of pain. The journal aims to increase the current knowledge about the pain mechanisms and encouraging the development of effective and safety treatments for pain.

The Scandinavian Journal of Pain (SJPAIN) publishes internationally relevant articles on all aspects of pain. The journal is the official quarterly publication of the Scandinavian Association for the Study of Pain and serves as a forum for original research on the nature of pain, pain mechanisms, and pain management.

Supportive Care in Cancer provides the most recent scientific and social information on all aspects of supportive care in cancer patients. The journal primarily covers medical, technical and surgical topics concerning supportive therapy and care which may supplement or substitute basic cancer treatment at all stages of the disease. Nursing, rehabilitative, psychosocial and spiritual issues of support are also covered.

Therapeutic Advances in Medical Oncology (TAM) is a peer-reviewed open access journal which focuses on pioneering efforts and innovative studies in the medical treatment of cancer. The journal is a member of the Committee on Publication Ethics (COPE).

Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed.

https://pubmed.ncbi.nlm.nih.gov/32007241/#:~:text=Free%20PMC%20article-,Abstract,address%20specific%20perioperative%20considerations%20for%20patients%20treated%20with%20immune%20checkpoint%20inhibitors.,-Keywords%3A%20adverse

Abstract
Introduction: Tumors invading the chest wall and pleura are often incurable, and treatment is targeted toward palliation of symptoms and control of pain. When patients develop tolerance or side effects to systemic opioid therapy, interventional techniques can better optimize a patient's pain. We performed a retrospective review of 146 patients from April 2004 to January 2014 who underwent diagnostic and therapeutic procedures for pain relief. Using four patients as a paradigm for neurolytic approaches to pain relief, we present a therapeutic algorithm for treating patients with intractable thoracic chest wall pain in the oncologic population.

Material and methods: For each patient, we describe the use of intercostal/paravertebral nerve blocks and neurolysis, pulsed radiofrequency ablation (PRFA) of the thoracic nerve roots, or intrathecal pump placement to successfully treat the patient's chest wall pain. Analysis of 146 patient charts is also performed to assess effectiveness of therapy.

Results: Seventy-nine percent of patients undergoing an intercostal nerve diagnostic blockade (with local anesthetic and steroid) stated that they had improved pain relief with 22% having prolonged pain relief (average of 21.5 days). Only 32% of successful diagnostic blockade patients elected to proceed to neurolysis, with a 62% success rate. Seven patients elected to proceed to intrathecal drug delivery.

Discussion: Intercostal nerve diagnostic blockade with local anesthetic and steroid may lead to prolonged pain relief in this population. Furthermore, depending on tumor location, we have developed a paradigm for the treatment of thoracic chest wall pain in the oncologic population.

Abstract
Introduction: Tumors invading the sacrum and/or ilium often represent incurable metastatic disease, and treatment is targeted toward palliation of symptoms and control of pain. As systemic opioid therapy is frequently inadequate and limited by side effects, a variety of interventional techniques are available to better optimize analgesia. Using six patients as a paradigm for interventional approaches to pain relief, we present a therapeutic algorithm for treating sacroiliac tumor-related pain in the oncologic population.

Methods: We describe the use of ultrasound-guided proximal sacroiliac joint corticosteroid injection, sacroiliac lateral branch radiofrequency ablation, percutaneous sacroplasty, and implantable neuraxial drug delivery devices to treat malignant sacroiliac pain in six patients. Pre- and postprocedure numerical rating scale (NRS) pain scores, duration of pain relief, and postprocedure pain medication requirements were studied for each patient.

Results: Each patient had marked improvement in their pain based on an average postprocedure NRS difference of six points. The average duration of pain relief was eight months. In all cases, opioid requirements decreased after the intervention.

Discussion: Depending on tumor location, burden of disease, and patient preference, patients suffering from metastatic disease to the sacrum may find benefit from use of ultrasound-guided proximal sacroiliac joint corticosteroid injection, sacroiliac lateral branch radiofrequency ablation, percutaneous sacroplasty, dorsal column stimulator leads, and/or implantable neuraxial drug delivery devices. We provide a paradigm for treatment in this patient population.