The Effects of WeChat-Based Teach-Back Health Education on Patients With Advanced Cancer Pain.

BACKGROUND: Providing effective health education is essential for patients with cancer-related pain. One solution is leveraging instant messaging tools for teach-back health education. OBJECTIVES: This study investigated the effects of WeChat-based teach-back health education on patients with advanced cancer who underwent patient-controlled intrathecal analgesia implantation and used hydromorphone. METHODS: This retrospective study evaluated 150 hospitalized patients with advanced cancer pain. Patients were classified into a conventional health education group (N = 50) and a teach-back group (N = 100) based on whether they received WeChat-based teach-back health education. Pain was rated using a numeric rating scale, and sleep quality was measured using the Pittsburgh Sleep Quality Index at one, two, and three months postdischarge. FINDINGS: Patients who received remote teach-back health education better managed their pain. Data also demonstrated improvements in patients' sleep quality and caregiver satisfaction, and reductions in the occurrence of adverse reactions.

Pharmacokinetic and neuroimmune pharmacogenetic impacts on slow-release morphine cancer pain control and adverse effects.

The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide concentration-response relationships in 506 cancer patients receiving controlled-release oral morphine. Morphine-3-glucuronide concentrations (standardised to 11 h post-dose) were higher in patients without pain control (median (interquartile range) 1.2 (0.7-2.3) versus 1.0 (0.5-1.9) µM, P = 0.006), whereas morphine concentrations were higher in patients with cognitive dysfunction (40 (20-81) versus 29 (14-60) nM, P = 0.02). TLR2 rs3804100 variant carriers had reduced odds (adjusted odds ratio (95% confidence interval) 0.42 (0.22-0.82), P = 0.01) of opioid adverse events. IL2 rs2069762 G/G (0.20 (0.06-0.52)), BDNF rs6265 A/A (0.15 (0.02-0.63)) and IL6R rs8192284 carrier (0.55 (0.34-0.90)) genotypes had decreased, and IL6 rs10499563 C/C increased (3.3 (1.2-9.3)), odds of sickness response (P ≤ 0.02). The study has limitations in heterogeneity in doses, sampling times and diagnoses but still suggests that pharmacokinetics and immune genetics co-contribute to morphine pain control and adverse effects in cancer patients.

Opioid Therapy for Cancer Pain in Vietnam: Knowledge, Attitudes, and Perceived Barriers Among Health Care Professionals, Policymakers, and Regulators.

PURPOSE: We aimed to assess knowledge, attitudes, and perceived barriers among health care professionals (HCPs), policymakers, and regulators in Vietnam related to opioid therapy for cancer pain. METHODS: We conducted a cross-sectional study in Vietnam from June to August 2022. Participants completed a questionnaire on their demographic characteristics, knowledge and attitudes toward opioid therapy, and barriers to accessing opioids for cancer pain. RESULTS: Two hundred seven HCPs and 15 policymakers/regulators completed the questionnaire. Poor knowledge about opioids in cancer pain was found in 63.3% of HCPs and 80.0% of policymakers/regulators. Poor knowledge was associated with a lack of training in cancer pain management or palliative care (PC; prevalence ratio [PR], 1.14 [95% CI, 1.04 to 1.24]). Negative attitudes toward opioid therapy in cancer pain were held by 64.7% of HCPs and 80.0% of policymakers/regulators. Negative attitudes were associated with the unavailability of oral morphine in the workplace (PR, 1.10 [95% CI, 1.01 to 1.20]). The most common major barriers reported were the absence of national policy on pain management and PC (34.7%), inadequate training in opioid use for cancer pain (33.8%), lockdown of health facilities during the COVID-19 pandemic (32.4%), limited opioid availability in local health facilities (32.4%), and excessively restrictive regulation of opioid dispensing in pharmacies (32.4%). CONCLUSION: This study found a knowledge deficit and negative attitudes toward opioid therapy for cancer pain among HCPs and policymakers/regulators. Improving education and training in opioid therapy is essential. Recognizing major barriers can guide strategies to enhance safe opioid accessibility for cancer pain management in Vietnam.

Cinobufotalin Capsule Combined with Zoledronic Acid in the Treatment of Pain Symptoms and Clinical Efficacy in Prostate Cancer Patients with Bone Metastases: A Retrospective Study.

OBJECTIVE: To retrospectively analyse the effects of cinobufotalin capsule combined with zoledronic acid on pain symptoms and clinical efficacy of prostate cancer patients with bone metastases. METHODS: Patients with prostate cancer with bone metastasis admitted to our hospital from January 2021 to December 2022 were selected as study subjects. They were divided into the control group (treated with zoledronic acid) and the combined group (cinobufotalin capsules were added on the control group basis) according to different recorded treatment methods. The efficacies of the two groups after matching, lumbar L1-4 bone mineral density (BMD), serum calcium, serum phosphorus, visual analogue scale (VAS) score and Karnofsky performance status (KPS) score before and after treatment were compared, and adverse reactions were statistically analysed. RESULTS: A total of 102 patients were included in the study, encompassing 52 patients in the combined group and 50 patients in the control group. After 1:1 preference score matching, 64 patients were included in the two groups. No significant difference in baseline data was found between the two groups (p > 0.05). The total effective rate of the combination group was higher than that of the control group (p < 0.05). No significant differences in L1-4 bone mineral density, serum calcium and phosphorus, VAS score and KPS score were observed between the two groups prior to treatment (p > 0.05). After treatment, the L1-4 bone mineral density (BMD) and KPS score of the combined group decreased to less than those of the control group, the VAS score was lower than that of the control group, and the serum calcium and phosphorus level increased but less than that of the control group (p < 0.05). No significant difference in adverse reactions was found between the two groups (p > 0.05). CONCLUSIONS: Cinobufotalin capsule combined with zoledronic acid had ideal efficacy in the treatment of prostate cancer in patients with bone metastasis. This approach could improve their bone density and quality of life, improve their calcium and phosphorus metabolism, reduce their pain symptoms and provide increased safety. It may have an important guiding role in formulating future clinical treatment plans for patients with prostate cancer and bone metastasis.

Patients' satisfaction with cancer pain treatment at adult oncologic centers in Northern Ethiopia; a multi-center cross-sectional study.

BACKGROUND: Patient satisfaction is an important indicator of the quality of healthcare. Pain is one of the most common symptoms among cancer patients that needs optimal treatment; rather, it compromises the quality of life of patients. OBJECTIVE: To assess the levels and associated factors of satisfaction with cancer pain treatment among adult patients at cancer centers found in Northern Ethiopia in 2023. METHODS: After obtaining ethical approval, a multi-center cross-sectional study was conducted at four cancer care centers in northern Ethiopia. The data were collected using an interviewer-administered structured questionnaire that included the Lubeck Medication Satisfaction Questionnaire (LMSQ). The severity of pain was assessed by a numerical rating scale from 0 to 10 with a pain score of 0 = no pain, 1-3 = mild pain, 4-6 = moderate pain, and 7-10 = severe pain Binary logistic regression analysis was employed, and the strength of association was described in an adjusted odds ratio with a 95% confidence interval. RESULT: A total of 397 cancer patients participated in this study, with a response rate of 98.3%. We found that 70.3% of patients were satisfied with their cancer pain treatment. Being married (AOR = 5.6, CI = 2.6-12, P < 0.001) and being single (never married) (AOR = 3.5, CI = 1.3-9.7, P = 0.017) as compared to divorced, receiving adequate pain management (AOR = 2.4, CI = 1.1-5.3, P = 0.03) as compared to those who didn't receive it, and having lower pain severity (AOR = 2.6, CI = 1.5-4.8, P < 0.001) as compared to those who had higher level of pain severity were found to be associated with satisfaction with cancer pain treatment. CONCLUSION: The majority of cancer patients were satisfied with cancer pain treatment. Being married, being single (never married), lower pain severity, and receiving adequate pain management were found to be associated with satisfaction with cancer pain treatment. It would be better to enhance the use of multimodal analgesia in combination with strong opioids to ensure adequate pain management and lower pain severity scores.

Effects of opioid drugs on immune function in cancer patients.

Opioid receptor agonists are often used when cancer patients undergo surgery or analgesic treatment. As analgesics in clinical care, opioids can provide intraoperative or to chronic cancer pain relief. Immune function plays an important role in anti-cancer therapy, with cellular immunity, comprised principally of T-lymphocytes and natural killer cells, representing the primary anti-cancer immune response. However, it remains unclear whether immune function is further affected with the use of opioids in already immunocompromised cancer patients. This article provides a review of the effects of commonly used clinical opioids, including morphine, oxycodone, fentanyl and tramadol, on immune function in cancer patients. It provides a summary of current evidence regarding the immunomodulatory effects of opioids in the cancer setting and mechanisms underlying these interactions.

Evaluating the Risk Index for Serious Prescription Opioid-Induced Respiratory Depression or Overdose in Patients with Cancer.

The Commercially Insured health Plan Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD) is an evidence-based tool to determine serious opioid-induced respiratory depression (OIRD) or overdose risk. The CIP-RIOSORD total score determines a risk class and estimates the probability for an OIRD event within the next 6 months. We performed a single-center, retrospective analysis to determine CIP-RIOSORD baseline scores and the most common predictive factors in patients with cancer. Patients (n = 160) were split into new consultations (n = 83, Group 1) versus the first documented follow-up consultation (n = 77, Group 2). Most patients were Caucasian women with metastatic gastrointestinal cancer. CIP-RIOSORD scores for Group 1 patients were 14.8 ± 15.2 (mean ± SD, risk class 4). Group 2 patients had higher CIP-RIOSORD scores (16.6 ± 14.9, risk class 4). For Group 1, the most common CIP-RIOSORD predictive factors were use of a long-acting opioid formulation (n = 24, 29%) and daily oral morphine equivalent (OME) ≥100 (n = 20, 24%); for Group 2, predictive factors were use of an antidepressant (n = 34, 44%) and a long-acting opioid formulation (n = 27, 35%). Based on the CIP-RIOSORD, there is a 15% probability of experiencing a serious OIRD event or overdose within the next 6 months.

Prevalence of Reluctance to Prescribe Opioids Among Physicians in Oncology Departments: A Descriptive Cross-Sectional Study From Turkey.

Cancer-related pain (CrP) is a significant public health problem, and opioids are the mainstay of CrP treatment. Considering the persistent problem of inadequate treatment of cancer pain in Turkey, the study was conducted to determine the prevalence of reluctance to prescribe opioids among physicians in oncology departments. The descriptive cross-sectional study included oncology residents and residents without oncology specialization in oncology departments. One thousand physicians were invited by e-mail to the Google Forms survey platform. Two hundred and seventy-eight physicians completed the survey and were included, of which 50% (n: 139) were female. More than half (n: 166; 59.7%) of them were oncology subspecialists. The prevalence of reluctance to prescribe opioids was calculated to be 38.1% (n: 106). A significant positive association was found between the factor associated with reluctance to prescribe opioids and fear of opioid use disorder (ß = 0.964; 95% CI = 0.362-1.566; p = .002). Reluctance to prescribe opioids was inversely related to the oncology subspecialty (ß = -0.878; 95% CI = -1.54 to -0.213; p = 0.010) and education about CrP and opioid management (ß = -1.707; 95% CI = -2.404 to -1.009; p = 0.01). Reluctance to prescribe opioids appears to be associated with a lack of knowledge and fear of opioid use disorder.

New opioid prescription claims and their clinical indications: results from health administrative data in Quebec, Canada, over 14 years.

OBJECTIVES: Describe new opioid prescription claims, their clinical indications and annual trends among opioid naïve adults covered by the Quebec's public drug insurance plan (QPDIP) for the fiscal years 2006/2007-2019/2020. DESIGN AND SETTING: A retrospective observational study was conducted using data collected between 2006/2007 and 2019/2020 within the Quebec Integrated Chronic Disease Surveillance System, a linkage administrative data. PARTICIPANTS: A cohort of opioid naïve adults and new opioid users was created for each study year (median number=2 263 380 and 168 183, respectively, over study period). INTERVENTION: No. MAIN OUTCOME MEASURE AND ANALYSES: A new opioid prescription was defined as the first opioid prescription claimed by an opioid naïve adult during a given fiscal year. The annual incidence proportion for each year was then calculated and standardised for age. A hierarchical algorithm was built to identify the most likely clinical indication for this prescription. Descriptive and trend analyses were performed. RESULTS: There was a 1.7% decrease of age-standardised annual incidence proportion during the study period, from 7.5% in 2006/2007 to 5.8% in 2019/2020. The decrease was highest after 2016/2017, reaching 5.5% annual percentage change. Median daily dose and days' supply decreased from 27 to 25 morphine milligram equivalent/day and from 5 to 4 days between 2006/2007 and 2019/2020, respectively. Between 2006/2007 and 2019/2020, these prescriptions' most likely clinical indications increased for cancer pain from 34% to 48%, for surgical pain from 31% to 36% and for dental pain from 9% to 11%. Inversely, the musculoskeletal pain decreased from 13% to 2%. There was good consistency between the clinical indications identified by the algorithm and prescriber's specialty or user's characteristics. CONCLUSIONS: New opioid prescription claims (incidence, dose and days' supply) decreased slightly over the last 14 years among QPDIP enrollees, especially after 2016/2017. Non-surgical and non-cancer pain became less common as their clinical indication.

Ghrelin Induces the Production of Hypothalamic NPY Through the AMPK-mTOR Pathway to Alleviate Cancer-induced Bone Pain.

BACKGROUND/AIM: Cancer-induced bone pain (CIBP) is one of the most common symptoms of bone metastasis of tumor cells. The hypothalamus may play a pivotal role in the regulation of CIBP. However, little is known about the exact mechanisms. MATERIALS AND METHODS: First, we established a CIBP model to explore the relationship among hypothalamic ghrelin, NPY and CIBP. Then, we exogenously administered NPY and NPY receptor antagonists to investigate whether hypothalamic NPY exerted an antinociceptive effect through binding to NPY receptors. Finally, we exogenously administered ghrelin to investigate whether ghrelin alleviated CIBP by inducing the production of hypothalamic NPY through the AMPK-mTOR pathway. Body weight, food intake and behavioral indicators of CIBP were measured every 3 days. Hypothalamic ghrelin, NPY and the AMPK-mTOR pathway were also measured. RESULTS: The expression of hypothalamic ghrelin and NPY was simultaneously decreased in cancer-bearing rats, which was accompanied by CIBP. Intracerebroventricular (i.c.v.) administration of NPY significantly alleviated CIBP in the short term. The antinociceptive effect of NPY was reversed with the i.c.v. administration of the Y1R and Y2R antagonists. The administration of ghrelin activated the AMPK-mTOR pathway and induced hypothalamic NPY production to alleviate CIBP. This effect of ghrelin on NPY and antinociception was reversed with the administration of a GHS-R1α antagonist. CONCLUSION: Ghrelin could induce the production of hypothalamic NPY through the AMPK-mTOR pathway to alleviate CIBP, which can provide a novel therapeutic mechanism for CIBP.

Intravenous administration of recombinant Phα1ß: Antinociceptive properties and morphine tolerance reversal in a cancer-associated pain model.

Cancer-related pain is considered one of the most prevalent symptoms for those affected by cancer, significantly influencing quality of life and treatment outcomes. Morphine is currently employed for analgesic treatment in this case, however, chronic use of this opioid is limited by the development of analgesic tolerance and adverse effects, such as digestive and neurological disorders. Alternative therapies, such as ion channel blockade, are explored. The toxin Phα1ß has demonstrated efficacy in blocking calcium channels, making it a potential candidate for alleviating cancer-related pain. This study aims to assess the antinociceptive effects resulting from intravenous administration of the recombinant form of Phα1ß (r-Phα1ß) in an experimental model of cancer-related pain in mice, tolerant or not to morphine. The model of cancer-induced pain was used to evaluate these effects, with the injection of B16F10 cells, followed by the administration of the r-Phα1ß, and evaluation of the mechanical threshold by the von Frey test. Also, adverse effects were assessed using a score scale, the rotarod, and open field tests. Results indicate that the administration of r-Phα1ß provoked antinociception in animals with cancer-induced mechanical hyperalgesia, with or without morphine tolerance. Previous administration of r-Phα1ß was able to recover the analgesic activity of morphine in animals tolerant to this opioid. r-Phα1ß was proved safe for these parameters, as no adverse effects related to motor and behavioral activity were observed following intravenous administration. This study suggests that the concomitant use of morphine and r-Phα1ß could be a viable strategy for pain modulation in cancer patients.

[Pharmacological pain management in cancer patients]. / Medikamentöse Schmerztherapie bei Patienten mit Tumorerkrankungen.

Pharmacological pain therapy in cancer patients is based on guideline recommendations, which, however, do not fully coincide in all aspects due to varying weighting of evidence. The present article discusses current issues including the decreasing significance of the World Health Organization (WHO) analgesic ladder, with its distinction between step 2 and 3 being increasingly questioned. Risks of nonopioid analgesics such as paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs), particularly in older populations, are discussed. Paracetamol may potentially reduce the effectiveness of immunotherapies. Aspects of administering analgesics via a feeding tube are considered. Recommendations for the treatment of episodic pain, transitioning between different opioids, and some relevant interactions are also discussed.

Effects of palliative intrathecal analgesia on patients with refractory cancer bone pain.

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).

5HT2A modulation attenuates pancreatic cancer induced pain mouse model by inhibiting HDAC.

PURPOSE: Patients have been severely suffered from cancer associated pain, and pancreatic cancer is the most severe form of cancer associated with pain. There are very few options available to manage it. The present report evaluated the effect of 5HT2A on pancreatic cancer associated pain. METHODS: Pancreatic cancer was induced by injecting SW 1,990 cells (~3×106 in a 20 µL suspension) into the pancreas and formed a 2-3-mm vesicle using an inoculator fitted with a 26-gauge needle in BALB/c-nu mice. Survival rate and body weight of the mice were observed. Pain behaviour testing was performed at the end of each week (third and fourth week) after surgery. Inflammatory mediators and HDAC 2 proteins were determined in the spinal tissue using quantitative real-time polymerase chain reaction. RESULTS: There was improvement in the survival rate and body weight in 5HT2A antagonist treated group than pancreatic cancer group of mice. Moreover, 5HT2A antagonist ameliorated the alteration in pain behaviour of pancreatic cancer mice. mRNA expression of HDAC2 and level of inflammatory cytokines were reduced in the spinal tissue of 5HT 2A antagonist treated group than pancreatic cancer group of mice. CONCLUSIONS: Data revealed that 5HT2A antagonist ameliorates pain associated with pancreatic cancer mice by HDAC inhibition and inflammatory cytokines. The result of investigation supports that modulation of 5HT2A receptor could be used clinically to protects neuropathic pain in pancreatic cancer.

Identifying provider, patient and practice factors that shape long-term opioid prescribing for cancer pain: a qualitative study of American and Australian providers.

INTRODUCTION: Prescribing long-term opioid therapy is a nuanced clinical decision requiring careful consideration of risks versus benefits. Our goal is to understand patient, provider and context factors that impact the decision to prescribe opioids in patients with cancer. METHODS: We conducted a secondary analysis of the raw semistructured interview data gathered from 42 prescribers who participated in one of two aligned concurrent qualitative studies in the USA and Australia. We conducted a two-part analysis of the interview: first identifying all factors influencing long-term prescribing and second open coding-related content for themes. RESULTS: Factors that influence long-term opioid prescribing for cancer-related pain clustered under three key domains (patient-related, provider-related and practice-related factors) each with several themes. Domain 1: Patient factors related to provider-patient continuity, patient personality, the patient's social context and patient characteristics including racial/ethnic identity, housing and socioeconomic status. Domain 2: Provider-related factors centred around provider 'personal experience and expertise', training and time availability. Domain 3: Practice-related factors included healthcare interventions to promote safer opioid practices and accessibility of quality alternative pain therapies. CONCLUSION: Despite the differences in the contexts of the two countries, providers consider similar patient, provider and practice-related factors when long-term prescribing opioids for patients with cancer. Some of these factors may be categorised as cognitive biases that may intersect in an already disadvantaged patient and exacerbate disparities in the treatment of their pain. A more systematic understanding of these factors and how they impact the quality of care can inform appropriate interventions.

Curcumin analogue NL04 inhibits spinal cord central sensitization in rats with bone cancer pain by inhibiting NLRP3 inflammasome activation and reducing IL-1ß production.

The management and therapy of bone cancer pain (BCP) remain formidable clinical challenges. Curcumin and its analogues have been shown to have anti-inflammatory and analgesic properties. In the present study, we investigated the efficacy of curcumin analogue NL04 (NL04) in modulating inflammation in spinal dorsal horn (SDH), thereby exploring its potential to reduce central sensitization of BCP in a rat model. Differing doses of NL04 and curcumin were administered intrathecally either once (on day 12 of BCP) or over seven consecutive days (from day 6-12 of BCP). Results indicated that the ED50 for NL04 and curcumin ameliorating BCP-induced mechanical hyperalgesia is 49.08 µg/kg and 489.6 µg/kg, respectively. The analgesic effects at various doses of NL04 lasted between 4 and 8 h, with sustained administration over a week maintaining pain relief for 1-4 days, while also ameliorating locomotor gait via gait analysis and reducing depressive and anxiety-like behaviors via open-field and light-dark transition tests. The analgesic effects at various doses of curcumin lasted 4 h, with sustained administration over a week maintaining pain relief for 0-2 days. ELISA, Western blotting, qPCR, and immunofluorescence assays substantiated that intrathecal administration of NL04 on days 6-12 of BCP dose-dependently lowered spinal IL-1ß and IL-18 levels and significantly reduced the expression of IKKß genes and proteins, as well as the downstream cleavage of the trans-Golgi network (TGN). Whole-cell patch-clamp results demonstrated that NL04 inhibits potassium ion efflux in rat primary spinal neurons. Thus, NL04 exhibits significant analgesic effects in a BCP rat model by downregulating IKKß expression and inhibiting neuronal potassium ion efflux, which, in turn, suppresses the activation of NLRP3 inflammasomes and reduces IL-1ß production, potentially ameliorating pain management in BCP.

Barriers to Pain Management as Perceived by Cancer and Noncancer Patients With Chronic Disease.

BACKGROUND: Pain is the most common symptom experienced by both cancer and non-cancer patients. A wide variety of barriers may hinder the optimal treatment of cancer and noncancer pain that are related to the health care system, health care providers, and patients. PURPOSE: To explore the barriers to pain management as perceived by patients with cancer and noncancer chronic diseases. METHOD: A descriptive, cross-sectional correlational design was employed to recruit a sample of 200 patients (n = 100 patients with cancer, n= 100 patients with noncancer) from two hospitals in Jordan. Patients filled out an Arabic version of Barriers Questionnaire II (ABQ-II). RESULTS: Harmful effects of medications were the greatest barrier to effective pain management, while fatalism had the lowest mean scores. Age was negatively correlated with physiological effects (r = -0.287, p < .01), communication (r = -0.263, p < .01), harmful effects (r = -0.284, p < .01), and the overall barrier score (r = -0.326, p < .01) among noncancer patients with chronic disease and (p > .05) for patients with cancer. Patients with cancer had higher mean scores (M = 2.12, SD = 0.78) in the fatalism subscale than those with noncancer chronic disease (M = 1.91, SD = 0.68), while patients with noncancer chronic disease had significantly higher mean scores (M = 2.78, SD = 0.78) in the communication subscale than patients with cancer (M = 2.49, SD = 0.65), (t = -2.899, p = .005). CONCLUSION: To improve the quality of care for patients who are in pain, it is recommended to address pain management barriers as they arise.

Scheduled and Breakthrough Opioid Use for Cancer Pain in an Inpatient Setting at a Tertiary Cancer Hospital.

Background: Our aim was to examine the frequency and prescription pattern of breakthrough (BTO) and scheduled (SCH) opioids and their ratio (BTO/SCH ratio) of use, prior to and after referral to an inpatient supportive care consult (SCC) for cancer pain management (CPM). Methods and Materials: Patients admitted at the MD Anderson Cancer Center and referred to a SCC were retrospectively reviewed. Cancer patients receiving SCH and BTO opioids for ≥24 h were eligible for inclusion. Patient demographics and clinical characteristics, including the type and route of SCH and BTO opioids, daily opioid doses (MEDDs) of SCH and BTO, and BTO/SCH ratios were reviewed in patients seen prior to a SCC (pre-SCC) and during a SCC. A normal BTO ratio was defined as 0.5-0.2. Results: A total of 665/728 (91%) patients were evaluable. Median pain scores (p < 0.001), BTO MEDDs (p < 0.001), scheduled opioid MEDDs (p < 0.0001), and total MEDDs (p < 0.0001) were higher, but the median number of BTO doses was fewer (2 vs. 4, p < 0.001), among patients seen at SCC compared to pre-SCC. A BTO/SCH ratio over the recommended ratio (>0.2) was seen in 37.5% of patients. The BTO/SCH ratios in the pre-SCC and SCC groups were 0.10 (0.04, 0.21) and 0.17 (0.10, 0.30), respectively, p < 0.001. Hydromorphone and Morphine were the most common BTO and SCH opioids prescribed, respectively. Patients in the early supportive care group had higher pain scores and MEDDs. Conclusions: BTO/SCH ratios are frequently prescribed higher than the recommended dose. Daily pain scores, BTO MEDDs, scheduled opioid MEDDs, and total MEDDs were higher among the SCC group than the pre-SCC group, but the number of BTO doses/day was lower.

Classical cannabinoid receptors as target in cancer-induced bone pain: a systematic review, meta-analysis and bioinformatics validation.

To test the hypothesis that genetic and pharmacological modulation of the classical cannabinoid type 1 (CB1) and 2 (CB2) receptors attenuate cancer-induced bone pain, we searched Medline, Web of Science and Scopus for relevant skeletal and non-skeletal cancer studies from inception to July 28, 2022. We identified 29 animal and 35 human studies. In mice, a meta-analysis of pooled studies showed that treatment of osteolysis-bearing males with the endocannabinoids AEA and 2-AG (mean difference [MD] - 24.83, 95% confidence interval [95%CI] - 34.89, - 14.76, p < 0.00001) or the synthetic cannabinoid (CB) agonists ACPA, WIN55,212-2, CP55,940 (CB1/2-non-selective) and AM1241 (CB2-selective) (MD - 28.73, 95%CI - 45.43, - 12.02, p = 0.0008) are associated with significant reduction in paw withdrawal frequency. Consistently, the synthetic agonists AM1241 and JWH015 (CB2-selective) increased paw withdrawal threshold (MD 0.89, 95%CI 0.79, 0.99, p < 0.00001), and ACEA (CB1-selective), AM1241 and JWH015 (CB2-selective) reduced spontaneous flinches (MD - 4.85, 95%CI - 6.74, - 2.96, p < 0. 00001) in osteolysis-bearing male mice. In rats, significant increase in paw withdrawal threshold is associated with the administration of ACEA and WIN55,212-2 (CB1/2-non-selective), JWH015 and AM1241 (CB2-selective) in osteolysis-bearing females (MD 8.18, 95%CI 6.14, 10.21, p < 0.00001), and treatment with AM1241 (CB2-selective) increased paw withdrawal thermal latency in males (mean difference [MD]: 3.94, 95%CI 2.13, 5.75, p < 0.0001), confirming the analgesic capabilities of CB1/2 ligands in rodents. In human, treatment of cancer patients with medical cannabis (standardized MD - 0.19, 95%CI - 0.35, - 0.02, p = 0.03) and the plant-derived delta-9-THC (20 mg) (MD 3.29, CI 2.24, 4.33, p < 0.00001) or its synthetic derivative NIB (4 mg) (MD 2.55, 95%CI 1.58, 3.51, p < 0.00001) are associated with reduction in pain intensity. Bioinformatics validation of KEGG, GO and MPO pathway, function and process enrichment analysis of mouse, rat and human data revealed that CB1 and CB2 receptors are enriched in a cocktail of nociceptive and sensory perception, inflammatory, immune-modulatory, and cancer pathways. Thus, we cautiously conclude that pharmacological modulators of CB1/2 receptors show promise in the treatment of cancer-induced bone pain, however further assessment of their effects on bone pain in genetically engineered animal models and cancer patients is warranted.

[The Fusion of Cancer Treatment and Cancer Pain Management].

Cancer treatment and cancer pain management constitute a dual approach aimed at improving the quality of life for patients. Their relationship must be complementary. Advances in cancer treatment have been remarkable, leading to increased survival rates in most types of cancer. However, there is a concern about the growing number of patients living with pain. Compared to the advancements in cancer treatment, progress in cancer pain management has been slow. As a basis for this observation, the available opioid analgesics and adjuvant pain-relieving medications have not increased significantly when compared to several years ago, and breakthrough treatments have yet to emerge. Even upon surveying guidelines both domestically and internationally, recommendations for cancer pain treatment are notably ambiguous. In recent years, however, opioid analgesics have proven to be a"double-edged sword". While they play a central role in cancer pain management, they also have cellular effects on tumor proliferation or suppression. This effect varies depending on the type of cancer, and it may be influenced differently by the content of cancer treatment, such as cytotoxic anticancer drugs, molecular targeted drugs, immune checkpoint inhibitors, and more. It may be time to recognize that cancer pain management has an impact on cancer treatment itself. Therefore, a crucial attitude is needed for closer collaboration between experts in cancer treatment and cancer pain management, fostering a co-creative approach in clinical and research settings. Professions such as pharmacists and nurses are essential for bridging this gap. To achieve the fusion beyond the integration of cancer treatment and cancer pain management, a transdisciplinary team, surpassing the boundaries of an interdisciplinary team, is necessary.