Clinical efficacy of EUS-guided celiac plexus neurolysis versus EUS-guided celiac ganglion irradiation with iodine-125 seeds for pain relief in advanced pancreatic cancer: A long-term retrospective study.

Background and Objective: To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (125I) seeds with absolute ethanol for relieving pain in patients with advanced pancreatic cancer. Methods: We retrospectively analyzed data of 81 patients with advanced pancreatic cancer who underwent EUS-CPN or EUS-125I implantation between January 2017 and December 2020. Postoperative pain was assessed using visual analog scale (VAS) scores; self-assessments of quality of life and the median survival time were compared between the 2 groups. Results: EUS-CPN and 125I implantation were performed in 43 and 38 patients, respectively. Postoperative VAS scores were significantly lower than the preoperative levels in both groups. One week after the operation, 26 patients (60.5%) in the EUS-CPN group achieved partial pain relief, whereas no patients in the EUS-125I seed group experienced pain relief. However, after 4 weeks postoperatively, VAS scores had decreased, and the rate of partial pain relief was higher for EUS-125I seeds than for EUS-CPN. Self-assessments of quality of life were similar in both groups during the first 1 month after the procedure. Conclusions: Both EUS-CPN and EUS-125I seeds can safely and effectively relieve pain in patients with advanced pancreatic cancer. Although EUS-125I seeds take additional time to show effects, the extent and duration of pain relief are better compared with CPN, and interestingly, the median survival time was different.

Scope of services provided to childhood cancer patients by the Brazilian Pediatric Palliative Care Network.

Introduction: Brazil is a developing and an Upper Middle Income, categorized by the World Bank. Therefore, it is a country that needs a special vision for children with oncological diseases who require Pediatric Palliative Care. This study aimed to understand the specificities of services that provide oncology services in comparison to those that do not provide oncological care. Methods: This is a descriptive, cross-sectional, and online survey study. A questionnaire was created by a multidisciplinary group of leaders from the Brazilian Pediatric Palliative Care Network and then the survey was distributed using a snowball strategy. Results: Of the 90 services that answered the questionnaire, 40 (44.4%) attended oncologic patients. The Southeast represented most of the services (57.57%), followed by the Northeast, with 18.89% (17 services), the South with 12.22% (11 services), and the Center West with 8.89% (8 services). No differences were observed in access to opioid prescriptions between the services. It was observed that those services that attended oncologic patients had a tendency to dedicate more time to Pediatric Palliative Care. Discussion: The distribution of services that cover oncology and those that do not, are similar in the different regions of Brazil. In Brazil, there are difficulties in accessing opioids in pediatrics: access to opioid prescriptions without differences revealed that even pediatric oncologists might have difficulty with this prescription, and this should improve. It is concluded that education in Pediatric Palliative Care is the key to improvements in the area.

Use of CYP2D6 substrates and inhibitors during pain management with analgesic opioids: Drug-drug interactions that lead to lack of analgesic effectiveness.

BACKGROUND: Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive pain management. We hypothesized that CYP2D6 phenotypes and concomitant use of CYP2D6 substrates or inhibitors would correlate with opioid analgesic outcomes. MATERIALS AND METHODS: An observational cross-sectional study was conducted with 263 adult chronic non cancer pain (CNCP) patients from a real-world pain unit under long-term CYP2D6-related opioid treatment (tramadol, hydromorphone, tapentadol or oxycodone). Metabolizer phenotype (ultrarapid [UM], normal [NM], intermediate [IM] or poor [PM]) was determined by the CYP2D6 genotype. The socio-demographic (sex, age, employment status), clinical (pain intensity and relief, neuropathic component, quality of life, disability, anxiety and depression), pharmacological (opioid doses and concomitant pharmacotherapy) and safety (adverse events) variables were recorded. RESULTS: The whole population (66 % female, 65 (14) years old, 70 % retired and 63 % attended for low back pain) were classified as PM (5 %), IM (32 %), NM (56 %) and UM (6 %). Multiple linear and logistic regressions showed higher pain intensity and neuropathic component at younger ages when using any CYP2D6 substrate (p = 0.022) or inhibitor (p = 0.030) drug, respectively, with poorer pain relief when CYP2D6 inhibitors (p=0.030) were present. CONCLUSION: The concomitant use of CYP2D6 substrates or inhibitors during opioid therapy for CNCP may result in lack of analgesic effectiveness. This aspect could be relevant for pharmacological decision making during CNCP management.

Pain in people seeking and receiving opioid agonist treatment: A systematic review and meta-analysis of prevalence and correlates.

BACKGROUND AND AIMS: People with opioid use disorder (OUD) commonly experience pain including chronic pain. Despite the high prevalence, few studies have systematically examined the prevalence and correlates of pain among people seeking or receiving opioid agonist treatment (OAT) for OUD. This review aimed to determine the prevalence of pain in this population globally, and estimate the association between chronic pain and other demographic and clinical characteristics. METHODS: Electronic searches were conducted in three databases (Medline, Embase and PsycINFO) from the inception until October 2022. Eligible studies reported prevalence rates of current and/or chronic pain. Meta-analyses examining the main prevalence estimates were conducted by Stata SE 18.0, and comorbid clinical conditions were analysed by Review Manager 5.4. RESULTS: Fifty-six studies (n participants = 35 267) from sixty-seven publications were included. Prevalence estimates of current and chronic pain were reported in 27 (48.2%) and 40 studies (71.4%), respectively. Most studies were conducted in North America (71.4%, n = 40) and used cross-sectional designs (64.3%, n = 36). Meta-analyses revealed a pooled prevalence of 60.0% (95% confidence interval [CI]: 52.0-68.0) for current pain and 44.0% [95% CI: 40.0-49.0] for chronic pain. Chronic pain was positively associated with older age (mean deviation of mean age: 2.39 years, 95% CI: 1.40-3.37; I2 = 43%), unemployment (odds ratio [OR] = 0.57, 95% CI: 0.42-0.76; I2 = 78%), more severe mental health symptoms (e.g. more severe depression (standardised mean difference [SMD] of mean scores: 0.45, 95% CI: 0.20-0.70; I2 = 48%) and anxiety symptoms (SMD: 0.52, 95% CI: 0.17-0.88; I2 = 67%), and hepatitis C (OR = 1.41, 95% CI: 1.03-1.94; I2 = 0%). No association was observed between chronic pain and the onset and type of OAT, geographic location, study design, survey year, participant age or use of specific pain assessment tools. CONCLUSIONS: There appears to be a high prevalence of pain among people seeking or receiving opioid agonist treatment for opioid use disorder compared with the general population, with positive associations for older age, unemployment, hepatitis C and the severity of some mental health symptoms.

Effectiveness of fentanyl buccal soluble film in cancer patients with inadequate breakthrough pain control.

BACKGROUND: Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. METHODS: The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. RESULTS: A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. CONCLUSION: FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. TRIAL REGISTRATION: This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

The Impact of Pain on Mobility in Patients with Cancer.

OBJECTIVES: Provide an overview of how pain impacts mobility in patients with cancer. METHODS: A literature search was conducted in PubMed and on Google Scholar using search terms, cancer pain with mobility, acute and chronic pain syndromes, enhanced recovery after surgery, nursing care, and rehabilitation. Peer-reviewed research studies, review articles, and pain guidelines and position papers were reviewed to provide an overview on cancer pain, its impact on mobility, and the nurse's role in managing pain and optimizing mobility and functional outcomes. RESULTS: Firty-two references were included in this overview. This body of literature is replete with studies on the management of pain; however, the tie between pain and mobility has not been well described aside from the breakthrough pain literature. This manuscript weaves these two important concepts together to better inform nurses and other clinicians regarding the importance of managing pain to even begin mobilizing patients, especially following surgery and for other painful conditions. CONCLUSIONS: Oncology nurses play an integral role in assessing and managing cancer pain. It is important for nurses to recognize how their pain management interventions lead to improved mobility and functioning in patients with cancer. IMPLICATIONS FOR NURSING PRACTICE: Nurses comprise the largest workforce around the globe and are well-equipped to assess and manage cancer pain in all cancer care settings. As leaders within the healthcare team, making recommendations to better control pain and communicating with other team members regarding the pain plan is essential in improving mobility in patients with cancer.

Medical marijuana in the treatment of cancer-associated symptoms.

OBJECTIVE: Previous cancer studies have indicated that medical marijuana addresses a significant unmet need, namely chronic pain treatment and conferring oncology supportive care. However, the clinical research evaluating medical marijuana is preliminary and requires further consideration. DATA SOURCES: We conducted a PubMed search primarily comprising retrospective and prospective studies, systematic reviews, and randomized clinical trials (RCTs) from approximately 2020-2023. The search included specific terms that incorporated medical marijuana, cancer treatment, cancer-related symptoms, pain management, and side effects. DATA SUMMARY: A total of 40 studies were included in the review, many of which were either of acceptable or good quality. Select investigations indicated that medical marijuana was associated with decreased overall pain levels and improvements in nausea and vomiting. Alternatively, the results from RCTs have found that the benefits from a placebo were equivalent to medical marijuana in both the treatment of cancer-related pain and providing an opioid-sparing effect. CONCLUSIONS: Despite the potential cancer-related benefits derived from medical marijuana, the study design and results for many of the investigations on which the evidence is based, were neither uniform nor conducted via RCTs; hence, the efficacy and appropriateness of medical marijuana in treating cancer-related conditions remain indeterminate.

A Novel Approach in Treating Phantom Limb Pain Using Erector Spinae Plane Block.

Phantom limb pain (PLP) is difficult to control, and patients frequently exhibit inadequate relief from medications or encounter unbearable side effects. We present here a novel application of erector spinae plane (ESP) block to manage PLP. Our patient is a 23-year-old, college student, diagnosed with high-grade osteosarcoma of the right humerus who underwent a right shoulder disarticulation. He reported PLP despite multimodal analgesia postoperatively. An ESP block using a high-frequency linear probe ultrasound was performed. A G23 spinal needle was advanced in-plane toward the right T3 transverse process. After negative aspiration, 20 mL of therapeutic solution containing bupivacaine 0.25%, lidocaine 1%, epinephrine 5 mcg/ml, and 40 mg methylprednisolone was injected. After the procedure, the patient reported that his PLP went down to NRS 1/10. He consistently reported to have an NRS score of 0-1/10 on succeeding consultations despite discontinuation of opioid and pregabalin. In literature, ESP block has been used as a regional technique for shoulder disarticulation surgery and other neuropathic pain conditions, but no account has shown its use for PLP treatment. The procedure was successfully done to alleviate the upper extremity phantom limb pain, significantly reduce analgesic requirements, and improve tolerance of physical therapy and overall quality of life.

Oxymatrine and Gut Microbiota Modulation: A Potential Therapeutic Strategy for Bone Cancer Pain Management.

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.

Impact of opioid analgesics on survival in cancer patients receiving immune checkpoint inhibitors.

PURPOSE: This study aimed to assess the effects of concurrent opioid analgesic (OA) use with immune checkpoint inhibitors (ICIs) on progression-free survival (PFS) and overall survival (OS). METHODS: In this observational retrospective study, we included advanced cancer patients who received ICIs at Hacettepe University Hospital's Department of Medical Oncology between June 2018 and January 2023. RESULTS: Our study included 375 recurrent or metastatic cancer patients treated with ICIs in the first, second line, or beyond. There were no significant differences between the OA-treated and OA-untreated groups regarding median age, age group, gender, primary tumor location, ICI type, or the presence of baseline liver and lung metastases. However, the OA-treated group exhibited a significantly higher proportion of patients who had received three or more prior treatments before initiating ICIs (p = 0.015). OA-Untreatment was significantly correlated with prolonged mPFS (6.83 vs. 4.30 months, HR 0.59, 95% CI 0.44-0.79, p < 0.001) and mOS (17.05 vs. 7.68 months, HR 0.60, 95% CI 0.45-0.80, p < 0.001). CONCLUSIONS: Our study demonstrates an association between the concurrent use of OAs and reduced OS and PFS in patients treated with ICIs. While OA treatment serves as a surrogate marker for higher disease burden, it may also suggest a potential biological relationship between opioids and immunotherapy efficacy.

Spinal cord stimulation attenuates paclitaxel-induced gait impairment and mechanical hypersensitivity via peripheral neuroprotective mechanisms in tumor-bearing rats.

BACKGROUND: Taxanes such as paclitaxel (PTX) induce dose-dependent chemotherapy-induced peripheral neuropathy (CIPN), which is associated with debilitating chronic pain and gait impairment. Increased macrophage-related proinflammatory activities have been reported to mediate the development and maintenance of neuropathic pain. While spinal cord stimulation (SCS) has been used for a number of pain conditions, the mechanisms supporting its use for CIPN remain to be elucidated. Thus, we aimed to examine whether SCS can attenuate Schwann cell-mediated and macrophage-mediated neuroinflammation in the sciatic nerve of Rowlette Nude (RNU) rats with PTX-induced gait impairment and mechanical hypersensitivity. METHODS: Adult male tumor-bearing RNU rats were used for this study examining PTX treatment and SCS. Gait and mechanical hypersensitivity were assessed weekly. Cytokines, gene expression, macrophage infiltration and polarization, nerve morphology and Schwann cells were examined in sciatic nerves using multiplex immunoassay, bulk RNA sequencing, histochemistry and immunohistochemistry techniques. RESULTS: SCS (50 Hz, 0.2 milliseconds, 80% motor threshold) attenuated the development of mechanical hypersensitivity (20.93±0.80 vs 12.23±2.71 grams, p<0.0096) and temporal gait impairment [swing (90.41±7.03 vs 117.27±9.71%, p<0.0076), and single stance times (94.92±3.62 vs 112.75±7.27%, p<0.0245)] induced by PTX (SCS+PTX+Tumor vs Sham SCS+PTX+Tumor). SCS also attenuated the reduction in Schwann cells, myelin thickness and increased the concentration of anti-inflammatory cytokine interleukin (IL)-10. Bulk RNA sequencing revealed differential gene expression after SCS, with 607 (59.2%) genes upregulated while 418 (40.8%) genes were downregulated. Notably, genes related to anti-inflammatory cytokines and neuronal growth were upregulated, while genes related to proinflammatory-promoting genes, increased M2γ polarization and decreased macrophage infiltration and Schwann cell loss were downregulated. CONCLUSION: SCS may attenuate PTX-induced pain and temporal gait impairment, which may be partly attributed to decreases in Schwann cell loss and macrophage-mediated neuroinflammation in sciatic nerves.

Knowledge and practical skills for cancer pain management among nurses on remote islands in Japan and related factors nationwide.

OBJECTIVE: To clarify the knowledge and practical skills needed for cancer pain management among nurses on remote islands in Japan and related factors nationwide. SETTING: Due to geographical factors, nurses working on remote islands in Japan have few opportunities to attend training programs, which makes it difficult to acquire the knowledge and practical skills needed to provide pain management for patients with cancer. METHODS: We conducted a self-administered questionnaire survey regarding knowledge and practical skills in pain management for patients with cancer. DESIGN: Cross-sectional study. PARTICIPANTS: Nurses working in cancer pain care in medical facilities and home care on remote islands throughout Japan. RESULTS: We analysed 128 responses. Regarding knowledge, the average accuracy level was 49.1%. Items with a low accuracy rate included selecting medicine according to the type of pain and the patient's condition. Regarding practice, the items with low scores included analgesics appropriate for the type of pain and relating physical pain to mental, social and spiritual aspects. The most common significant factor in both knowledge and practice was related to postgraduate training. CONCLUSIONS: These findings suggest that to improve the knowledge and practical skills for cancer pain management among nurses on remote islands in Japan, it is necessary to incorporate clinical reasoning into basic education and establish remote education systems and consultation systems with other facilities.

Validity of central pain processing biomarkers for predicting the occurrence of oncological chronic pain: a study protocol.

BACKGROUND: Despite recent improvements in cancer detection and survival rates, managing cancer-related pain remains a significant challenge. Compared to neuropathic and inflammatory pain conditions, cancer pain mechanisms are poorly understood, despite pain being one of the most feared symptoms by cancer patients and significantly impairing their quality of life, daily activities, and social interactions. The objective of this work was to select a panel of biomarkers of central pain processing and modulation and assess their ability to predict chronic pain in patients with cancer using predictive artificial intelligence (AI) algorithms. METHODS: We will perform a prospective longitudinal cohort, multicentric study involving 450 patients with a recent cancer diagnosis. These patients will undergo an in-person assessment at three different time points: pretreatment, 6 months, and 12 months after the first visit. All patients will be assessed through demographic and clinical questionnaires and self-report measures, quantitative sensory testing (QST), and electroencephalography (EEG) evaluations. We will select the variables that best predict the future occurrence of pain using a comprehensive approach that includes clinical, psychosocial, and neurophysiological variables. DISCUSSION: This study aimed to provide evidence regarding the links between poor pain modulation mechanisms at precancer treatment in patients who will later develop chronic pain and to clarify the role of treatment modality (modulated by age, sex and type of cancer) on pain. As a final output, we expect to develop a predictive tool based on AI that can contribute to the anticipation of the future occurrence of pain and help in therapeutic decision making.

Cervical Epidural Anesthesia in the Management of a Patient With Breast Cancer With Cardiac Dysfunction: A Case Report.

As one of the most common cancers in the world, breast cancer management is fraught with difficulties. Modified radical mastectomy (MRM) is one of the surgical procedures that is essential to the treatment of breast cancer. Cardiovascular issues, especially a reduced ejection fraction (EF), make these procedures more complex. Due to their increased vulnerability to adverse cardiac events during surgery, it is imperative to preserve hemodynamic stability and reduce physiological stress responses in these patients. A promising option in this changing field of anesthetic techniques is cervical epidural anesthesia (CEA). It effectively reduces hemodynamic fluctuations frequently linked to general anesthesia while providing analgesia. We report the case of an elderly patient with decreased EF and breast cancer scheduled for an MRM. To ensure the best possible outcomes in complex cases, the case report covers preoperative assessment, anesthesia technique, intraoperative management, and postoperative outcomes. This highlights the critical significance of customizing anesthesia and surgical procedures, informed consent, and meticulous postoperative pain management, and ultimately advocates for the broader implementation of CEA in such settings.

Discovery of a CCR2-targeting pepducin therapy for chronic pain.

Targeting the CCL2/CCR2 chemokine axis has been shown to be effective at relieving pain in rodent models of inflammatory and neuropathic pain, therefore representing a promising avenue for the development of non-opioid analgesics. However, clinical trials targeting this receptor for inflammatory conditions and painful neuropathies have failed to meet expectations and have all been discontinued due to lack of efficacy. To overcome the poor selectivity of CCR2 chemokine receptor antagonists, we generated and characterized the function of intracellular cell-penetrating allosteric modulators targeting CCR2, namely pepducins. In vivo, chronic intrathecal administration of the CCR2-selective pepducin PP101 was effective in alleviating neuropathic and bone cancer pain. In the setting of bone metastases, we found that T cells infiltrate dorsal root ganglia (DRG) and induce long-lasting pain hypersensitivity. By acting on CCR2-expressing DRG neurons, PP101 attenuated the altered phenotype of sensory neurons as well as the neuroinflammatory milieu of DRGs, and reduced bone cancer pain by blocking CD4+ and CD8+ T cell infiltration. Notably, PP101 demonstrated its efficacy in targeting the neuropathic component of bone cancer pain, as evidenced by its anti-nociceptive effects in a model of chronic constriction injury of the sciatic nerve. Importantly, PP101-induced reduction of CCR2 signaling in DRGs did not result in deleterious tumor progression or adverse behavioral effects. Thus, targeting neuroimmune crosstalk through allosteric inhibition of CCR2 could represent an effective and safe avenue for the management of chronic pain.

Dangerous Variation or Patient-Centered Care? Palliative Care and Pain Providers' Comfort, Experiences, and Approaches when Treating Cancer Pain With Coexisting Aberrant Behaviors.

BACKGROUND: Patients with cancer-related pain are at high risk for aberrant drug use behaviors (ADB), including self-escalation, diversion and concurrent illicit substance or opioid misuse; however, limited evidence is available to guide opioid prescribing for patients with life-limiting illness and concurrent or suspected ADB. We sought to characterize how specialists evaluate for and manage these high-risk behaviors in patients with cancer-related pain. METHODS: We conducted telephonic semi-structured interviews with palliative care and pain medicine providers. Participants discussed their own comfort and experience level with identifying and managing ADB in patients with life-limiting illness. They were subsequently presented with a series of standardized scenarios and asked to describe their concerns and management strategies. RESULTS: 95 interdisciplinary pain and palliative care specialists were contacted; 37 agreed to participate (38.9%). Analysis of interview contents revealed several central themes: (1) widespread discomfort and anxiety regarding safe and compassionate opioid prescribing for high-risk patients, (2) belief that widely used risk-mitigation tools such as opioid contracts and urine drug screens provided inadequate support for decision-making, and (3) lack of institutional and organizational support and guidance for safe prescribing strategies. Most clinicians reported self-education regarding addiction and alternative prescribing/pain management strategies. Providers varied widely in their willingness to discontinue opioid prescribing in a patient with aberrant behavior and pain associated with life-limiting illness. CONCLUSION: Providers caring for patients demonstrating ADB and cancer-related pain struggle to balance safe prescribing with symptom management. Increased guidance is needed regarding opioid prescribing, monitoring, and discontinuation in high-risk patients.

ABCB1 genetic polymorphisms affect opioid requirement by altering function of the intestinal P-glycoprotein.

The association between polymorphisms of the human ATP binding cassette subfamily B member 1 (ABCB1) gene and opioid response has attracted intense attention recently. As the ABCB1 gene encodes for the transporter P-glycoprotein in the brain and intestine involved in the pharmacokinetics of opioids, we investigated the effects of ABCB1 genetic polymorphisms on doses of opioids for pain relief and determined which pharmacokinetic process was affected in cancer pain patients. Sixty-eight cancer pain patients admitted for intrathecal therapy (ITT) were included. The association between ABCB1 genetic polymorphisms (C3435T, C1236T, G2677T/A and A61G) and systemic doses of opioids before ITT were investigated. Concentrations of oxycodone in plasma and cerebrospinal fluid (CSF) were determined by HPLC-MS/MS in 17 patients treated with oral oxycodone before ITT, and the influences of ABCB1 genetic polymorphisms on plasma-concentration to oral-dose ratios and CSF-concentration to plasma-concentration ratios of oral oxycodone were further analyzed. ABCB1 C3435T and G2677T/A polymorphisms were significantly associated with systemic doses of opioids before ITT, which coincided with the influences of ABCB1 C3435T and G2677T/A polymorphisms on the ratios of plasma-concentration to oral-dose. However, no significant difference was found in ratios of CSF-concentration to plasma-concentration among ABCB1 SNP genotypes. The present study provided the first evidence that ABCB1 C3435T and G2677T/A polymorphisms affect opioid requirement in cancer pain patients via altering transportation function of P-glycoprotein in the intestine, which will further expand our knowledge about pharmacokinetics of opioids and could contribute to the individualization of opioids use.

The TREK-1 potassium channel is involved in both the analgesic and anti-proliferative effects of riluzole in bone cancer pain.

BACKGROUND: The metastasis of tumors into bone tissue typically leads to intractable pain that is both very disabling and particularly difficult to manage. We investigated here whether riluzole could have beneficial effects for the treatment of prostate cancer-induced bone pain and how it could influence the development of bone metastasis. METHODS: We used a bone pain model induced by intratibial injection of human PC3 prostate cancer cells into male SCID mice treated or not with riluzole administered in drinking water. We also used riluzole in vitro to assess its possible effect on PC3 cell viability and functionality, using patch-clamp. RESULTS: Riluzole had a significant preventive effect on both evoked and spontaneous pain involving the TREK-1 potassium channel. Riluzole did not interfere with PC3-induced bone loss or bone remodeling in vivo. It also significantly decreased PC3 cell viability in vitro. The antiproliferative effect of riluzole is correlated with a TREK-1-dependent membrane hyperpolarization in these cells. CONCLUSION: The present data suggest that riluzole could be very useful to manage evoked and spontaneous hypersensitivity in cancer-induced bone pain and has no significant adverse effect on cancer progression.

PaiNEd app. Assessing central sensitization in survivors of breast cancer: A reliability study.

Introduction: Pain is a common adverse event in survivors of breast cancer (sBCs). As there is no gold standard to assess pain experience predominantly related to central sensitization (CS) symptoms, we designed the PaiNEd app, which includes an algorithm to report whether patients are under predominant CS pain mechanisms. Objective: We aimed to assess the reliability of the PaiNEd app to estimate whether sBC pain experience is predominantly related to CS symptoms. Methods: An observational, descriptive reliability design was employed to assess the inter- and intrarater reliability of the PaiNEd app. This app includes an algorithm that considers the number of painful body parts and some questionnaires related to pain, such as the Numeric Pain-Rating Scale, the Brief Pain Inventory, the Tampa Scale for Kinesiophobia, the Pain Catastrophizing Scale, and the Central Sensitization Inventory (CSI). Results: A total of 21 sBCs with persistent pain were recruited. We observe a general trend of close agreement between the paper-based and app-based formats (ICCs ranged between 0.802 and 0.972; Cronbach's alpha ranged between 0.797 and 0.971). Test-retest reliabilities were moderate to excellent (ICCs ranged between 0.510 and 0.941; Cronbach's alpha ranged between 0.499 and 0.938). The agreement between the categorization of the CS algorithm and the CSI (cut-off point ≥ 40 for CS symptoms) was 95.24%. Conclusion: The PaiNEd app emerges as a robust tool for evaluating pain experience predominantly related to CS and pain-related symptoms in sBCs. Its demonstrated reliability not only bolsters its utility but also signifies its potential as a valuable asset for healthcare professionals engaged in pain education programs.