ABSTRACT
Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.
Subject(s)
Analgesics, Opioid , Cancer Pain , Humans , Analgesics, Opioid/therapeutic use , Analgesics, Opioid/adverse effects , Cancer Pain/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Nociceptive Pain/drug therapy , Neoplasms/complications , Pain Management/methodsABSTRACT
Multiple myeloma (MM) is a neoplasia of B plasma cells that often induces bone pain. However, the mechanisms underlying myeloma-induced bone pain (MIBP) are mostly unknown. Using a syngeneic MM mouse model, we show that periosteal nerve sprouting of calcitonin gene-related peptide (CGRP+) and growth associated protein 43 (GAP43+) fibers occurs concurrent to the onset of nociception and its blockade provides transient pain relief. MM patient samples also showed increased periosteal innervation. Mechanistically, we investigated MM induced gene expression changes in the dorsal root ganglia (DRG) innervating the MM-bearing bone of male mice and found alterations in pathways associated with cell cycle, immune response and neuronal signaling. The MM transcriptional signature was consistent with metastatic MM infiltration to the DRG, a never-before described feature of the disease that we further demonstrated histologically. In the DRG, MM cells caused loss of vascularization and neuronal injury, which may contribute to late-stage MIBP. Interestingly, the transcriptional signature of a MM patient was consistent with MM cell infiltration to the DRG. Overall, our results suggest that MM induces a plethora of peripheral nervous system alterations that may contribute to the failure of current analgesics and suggest neuroprotective drugs as appropriate strategies to treat early onset MIBP.SIGNIFICANCE STATEMENT Multiple myeloma (MM) is a painful bone marrow cancer that significantly impairs the quality of life of the patients. Analgesic therapies for myeloma-induced bone pain (MIBP) are limited and often ineffective, and the mechanisms of MIBP remain unknown. In this manuscript, we describe cancer-induced periosteal nerve sprouting in a mouse model of MIBP, where we also encounter metastasis to the dorsal root ganglia (DRG), a never-before described feature of the disease. Concomitant to myeloma infiltration, the lumbar DRGs presented blood vessel damage and transcriptional alterations, which may mediate MIBP. Explorative studies on human tissue support our preclinical findings. Understanding the mechanisms of MIBP is crucial to develop targeted analgesic with better efficacy and fewer side effects for this patient population.
Subject(s)
Bone Diseases , Multiple Myeloma , Nerve Tissue , Humans , Mice , Male , Animals , Multiple Myeloma/complications , Multiple Myeloma/metabolism , Multiple Myeloma/pathology , Quality of Life , Pain/metabolism , Nerve Tissue/metabolism , Nerve Tissue/pathology , Ganglia, Spinal/metabolismABSTRACT
Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.
Subject(s)
Cancer Pain , Electroacupuncture , Neoplasms , Neuropeptides , Rats , Humans , Mice , Animals , Cancer Pain/etiology , Cancer Pain/therapy , Cancer Pain/metabolism , Nociception , Mice, Nude , Rats, Sprague-Dawley , Pain/metabolism , Hyperalgesia/complications , Hyperalgesia/therapy , Hyperalgesia/chemically induced , Analgesics/metabolism , Inflammation/metabolism , Spinal Cord/metabolismABSTRACT
BACKGROUND: Opioid pain management in cancer survivorship is a complex and understudied topic. METHODS: The authors conducted in-depth, qualitative interviews to understand clinician approaches to opioid pain management in chronic cancer pain and to generate ideas for improvement. They used a rigorous, inductive, qualitative, descriptive approach to examine clinician (n = 20) perspectives about opioid pain management in survivorship, including oncologists (n = 5), palliative care clinicians (n = 8), primary care clinicians (n = 5), and pain management specialists (n = 2). RESULTS: The findings indicated that no consistent medical home exists for chronic pain management in cancer survivors and that there are fundamental differences in how each subspecialty approaches chronic pain management in survivorship (e.g., "Do we think of this as noncancer pain or cancer pain? This is in this limbo zone-this gray zone-because it's cancer-related pain, right?"). Simultaneously, clinicians are influenced by their peers' perceptions of their opioid prescribing decisions, sparking intraprofessional tension when disagreement occurs. In these instances, clinicians described overthinking and doubting their clinical decision-making as well as a sense of judgment, pressure, and/or shame. Finally, clinicians acknowledged a fear of consequences for opioid prescribing decisions. Specifically, participants cited conflict with patients, sometimes escalating to aggression and threats of violence, as well as potential disciplinary actions and/or legal consequences. CONCLUSIONS: Participants suggested that opportunities to improve chronic cancer pain care include developing clear, systematic guidance for chronic cancer pain management, facilitating clinician communication and consultation, creating tailored survivorship care plans in partnership with patients, and developing accessible, evidence-based, complementary pain treatments.
Subject(s)
Analgesics, Opioid , Cancer Pain , Cancer Survivors , Chronic Pain , Pain Management , Practice Patterns, Physicians' , Humans , Analgesics, Opioid/therapeutic use , Cancer Pain/drug therapy , Chronic Pain/drug therapy , Pain Management/methods , Cancer Survivors/psychology , Male , Female , Survivorship , Qualitative Research , Middle Aged , Attitude of Health Personnel , Neoplasms/complications , Neoplasms/drug therapy , Neoplasms/psychology , AdultABSTRACT
Cancer is a leading cause of morbidity and mortality worldwide, with pain experienced by most patients undergoing cancer treatment. Opioids are the recommended treatment for cancer pain management, but recent studies suggest a negative association between opioid use and survival rates among patients undergoing immunotherapy. However, conclusions cannot be drawn regarding causality from these observational data. Immunotherapy, which boosts the body's immune system to fight cancer cells, has emerged as a promising treatment option for all types of cancer. Immune checkpoint inhibitors (ICIs) can activate the anticancer function of exhausted T cells and have shown remarkable survival benefits in patients with multiple malignancies. However, a recent systematic review and meta-analysis suggested that the use of opioids during ICI treatment has an adverse effect on patient prognosis, while the use of NSAIDs is not significantly associated with the prognosis in patients treated with ICIs. These reviews have major limitations due to the retrospective nature of the studies and the multiple factors that can influence the phenomenon. Therefore, caution is required when interpreting results from retrospective data on drug interactions. The findings of this study are alarming and potentially harmful to patients with cancer suffering from pain or other symptoms requiring opioid drugs.
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OBJECTIVE: Unsafe opioid-related practices can lead to abuse, diversion, and accidental overdoses. In this study, we aimed to describe the patterns and beliefs regarding the storage, disposal, and use of opioids among Chinese patients with cancer in their home settings, which remain unclear. METHODS: A multicenter cross-sectional survey was conducted in Hubei Province from October 2022 to June 2023. We collected information on the storage, disposal, and use of opioids among cancer pain inpatients in the oncology department. Logistic regression was used to estimate the factors associated with unsafe disposal and use of opioids. RESULTS: The survey included 221 patients with a median age of 62 years. Only 3.2% stored their opioids under lock and key, and 49.8% were unaware of proper disposal methods. Nearly one-fifth (19.5%) reported having received information on the safe storage (14.0%) and/or disposal (10.0%) of opioids. A total of 44.3% reported unsafe use by sharing (1.8%), losing (4.1%), or taking opioids at a higher dose than prescribed (42.5%). Patients who did not receive information on the safe disposal of opioids (ORâ =â 4.57, Pâ =â .0423), had a history of alcohol use (ORâ =â 1.91, Pâ =â .0399), and used opioids other than morphine (ORâ =â 2.31, Pâ =â .0461) had higher odds of unsafe disposal practices. Individuals with an associate degree/bachelor's degree or above were less likely to dispose of (ORâ =â 0.36, Pâ =â .0261) and use (ORâ =â 0.31, Pâ =â .0127) opioids unsafely. CONCLUSION: A significant proportion of Chinese patients with cancer exhibit unsafe practices in the storage, disposal, and use of opioids. The study highlights an urgent need for implementing routine education programs and drug "take-back" initiatives to improve opioid-related practices.
Subject(s)
Analgesics, Opioid , Neoplasms , Humans , Cross-Sectional Studies , Male , Analgesics, Opioid/adverse effects , Analgesics, Opioid/therapeutic use , Female , Middle Aged , China/epidemiology , Aged , Neoplasms/epidemiology , Neoplasms/drug therapy , Cancer Pain/drug therapy , Adult , Drug Storage/standards , Drug Storage/methods , Surveys and QuestionnairesABSTRACT
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.
Subject(s)
Cancer Pain , Patient Satisfaction , Humans , Cross-Sectional Studies , Male , Female , Ethiopia/epidemiology , Cancer Pain/drug therapy , Cancer Pain/psychology , Middle Aged , Adult , Patient Satisfaction/statistics & numerical data , Pain Management/methods , Surveys and Questionnaires , Quality of Life , Aged , Neoplasms/complications , Neoplasms/drug therapy , Neoplasms/psychology , Young Adult , Pain Measurement , Cancer Care Facilities/statistics & numerical data , AdolescentABSTRACT
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.
Subject(s)
Cancer Pain , Chronic Pain , Adult , Female , Humans , Male , Middle Aged , Artificial Intelligence , Biomarkers , Cancer Pain/diagnosis , Chronic Pain/diagnosis , Chronic Pain/etiology , Electroencephalography , Longitudinal Studies , Neoplasms/complications , Pain Measurement/methods , Prospective Studies , Quality of Life , Multicenter Studies as TopicABSTRACT
Bone cancer pain (BCP) represents a prevalent symptom among cancer patients with bone metastases, yet its underlying mechanisms remain elusive. This study investigated the transcriptional regulation mechanism of Kv7(KCNQ)/M potassium channels in DRG neurons and its involvement in the development of BCP in rats. We show that HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes, which encode Kv7(KCNQ)/M potassium channels in dorsal root ganglion (DRG), contributes to the sensitization of DRG neurons and the pathogenesis of BCP in rats. Also, HDAC2 requires the formation of a corepressor complex with MeCP2 and Sin3A to execute transcriptional regulation of kcnq2/kcnq3 genes. Moreover, EREG is identified as an upstream signal molecule for HDAC2-mediated kcnq2/kcnq3 genes transcription repression. Activation of EREG/EGFR-ERK-Runx1 signaling, followed by the induction of HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes in DRG neurons, leads to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. Consequently, the activation of EREG/EGFR-ERK-Runx1 signaling, along with the subsequent transcriptional repression of kcnq2/kcnq3 genes by HDAC2 in DRG neurons, underlies the sensitization of DRG neurons and the pathogenesis of BCP in rats. These findings uncover a potentially targetable mechanism contributing to bone metastasis-associated pain in cancer patients.
Subject(s)
Bone Neoplasms , Cancer Pain , ErbB Receptors , Ganglia, Spinal , Histone Deacetylase 2 , KCNQ2 Potassium Channel , Animals , Histone Deacetylase 2/metabolism , Histone Deacetylase 2/genetics , KCNQ2 Potassium Channel/genetics , KCNQ2 Potassium Channel/metabolism , Ganglia, Spinal/metabolism , Ganglia, Spinal/pathology , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Bone Neoplasms/secondary , Bone Neoplasms/pathology , Rats , Cancer Pain/genetics , Cancer Pain/metabolism , Cancer Pain/pathology , ErbB Receptors/metabolism , ErbB Receptors/genetics , KCNQ3 Potassium Channel/genetics , KCNQ3 Potassium Channel/metabolism , Transcription, Genetic , Methyl-CpG-Binding Protein 2/genetics , Methyl-CpG-Binding Protein 2/metabolism , Sin3 Histone Deacetylase and Corepressor Complex/genetics , Signal Transduction/genetics , Core Binding Factor Alpha 2 Subunit/genetics , Core Binding Factor Alpha 2 Subunit/metabolism , Humans , Female , Extracellular Signal-Regulated MAP Kinases/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism , Rats, Sprague-Dawley , MAP Kinase Signaling System/geneticsABSTRACT
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.
Subject(s)
Chronic Pain , Ganglia, Spinal , Neuralgia , Receptors, CCR2 , Animals , Receptors, CCR2/antagonists & inhibitors , Receptors, CCR2/metabolism , Chronic Pain/drug therapy , Ganglia, Spinal/drug effects , Ganglia, Spinal/metabolism , Neuralgia/drug therapy , Neuralgia/metabolism , Humans , Cancer Pain/drug therapy , Bone Neoplasms/drug therapy , Bone Neoplasms/secondary , Analgesics/pharmacology , Analgesics/therapeutic use , Male , Mice , Female , Mice, Inbred C57BLABSTRACT
Chronic pain has been proven to be an independent disease, other than an accompanying symptom of certain diseases. Interleukin-18 (IL-18), a pro-inflammatory cytokine with pleiotropic biological effects, participates in immune modulation, inflammatory response, tumor growth, as well as the process of chronic pain. Compelling evidence suggests that IL-18 is upregulated in the occurrence of chronic pain. Antagonism or inhibition of IL-18 expression can alleviate the occurrence and development of chronic pain. And IL-18 is located in microglia, while IL-18R is mostly located in astrocytes in the spinal cord. This indicates that the interaction between microglia and astrocytes mediated by the IL-18/IL-18R axis is involved in the occurrence of chronic pain. In this review, we described the role and mechanism of IL-18 in different types of chronic pain. This review provides strong evidence that IL-18 is a potential therapeutic target in pain management.
Subject(s)
Chronic Pain , Interleukin-18 , Humans , Interleukin-18/metabolism , Interleukin-18/pharmacology , Chronic Pain/metabolism , Cytokines/metabolism , Microglia , AstrocytesABSTRACT
Cancer-related pain has a significant impact on quality of life for patients with cancer. In populations without cancer, there are documented pain inequities associated with minoritized racial and/or ethnic groups, women, and low socioeconomic status. However, our understanding of pain inequities specifically among patients with cancer remains incomplete. We narratively synthesized published quantitative research on cancer-related pain inequities in the US in the past decade. A search identified 17 English-language articles examining pain for patients with various cancer types at different treatment stages. Our review revealed mixed findings comparing cancer-related pain by racial group (e.g., Black vs White) and sex (male vs female), but consistent findings indicating that people with lower (vs higher) socioeconomic status and younger (vs older) patients report more cancer-related pain. Research on cancer pain among sexual and gender minorities remains scant. Key research gaps include a need for more research that incorporates an intersectional perspective by exploring intersecting subgroups and measuring social and structural processes that drive pain inequities. These findings underscore an important need for researchers to use an intersectional approach to cancer pain to help elucidate key populations at-risk for exacerbated cancer-related pain and identify ways to mitigate social and structural processes that drive these inequities.
There are known differences in pain experiences among people from different racial or ethnic groups, sex (male or female) or gender (men or women), and socioeconomic groups such as low income people. However, we don't fully understand these differences among cancer patients yet. This review looks at the past 10 years of research on how cancer-related pain may differ for people from different sociodemographic groups. We collected information from 17 studies in the US that looked at how pain from different types of cancer and different stages of treatment may differ for people from these different groups. We found mixed results when comparing pain between racial groups and sex and/or gender groups, but consistently found that people with lower incomes and younger patients reported more pain. There's not much research on how cancer pain affects sexual and gender minorities (LGBTQ+ people). Our review suggests that we need an intersectional approach to best understand cancer-related pain in order to best address how structural discrimination influences pain. Researchers should use an intersectional perspective, which will help us find out who's most at risk of severe cancer pain and find ways to help them better.
Subject(s)
Cancer Pain , Humans , Cancer Pain/therapy , Male , Female , Neoplasms/complications , Quality of Life , Healthcare Disparities , Health InequitiesABSTRACT
OBJECTIVE: Pain is common among people with advanced cancer. While opioids provide significant relief, incorporating psycho-behavioral treatments may improve pain outcomes. We examined patients' experiences with pain self-management and how their self-management of chronic, cancer-related pain may be complemented by behavioral mobile health (mHealth) interventions. METHODS: We conducted semi-structured qualitative interviews with patients with advanced cancer and pain. Each participant reviewed content from our behavioral mHealth application for cancer pain management and early images of its interface. Participants reflected on their experiences self-managing cancer pain and on app content. Interviews were transcribed verbatim and analyzed using a combination of inductive and deductive thematic analysis. RESULTS: Patients (n = 28; 54% female; mean age = 53) across two geographic regions reported using psychological strategies (e.g., reframing negative thoughts, distraction, pain acceptance, social support) to manage chronic cancer-related pain. Patients shared their perspectives on the integration of psycho-behavioral pain treatments into their existing medical care and their experiences with opioid hesitancy. Patient recommendations for how mHealth interventions could best support them coalesced around two topics: 1.) convenience in accessing integrated pharmacological and psycho-behavioral pain education and communication tools and 2.) relevance of the specific content to their clinical situation. CONCLUSIONS: Integrated pharmacological and psycho-behavioral pain treatments were important to participants. This underscores a need to coordinate complimentary approaches when developing cancer pain management interventions. Participant feedback suggests that an mHealth intervention that integrates pain treatments may have the capacity to increase advanced cancer patients' access to destigmatizing, accessible care while improving pain self-management.
Subject(s)
Cancer Pain , Neoplasms , Telemedicine , Humans , Female , Middle Aged , Male , Pain Management/methods , Cancer Pain/therapy , Cancer Pain/psychology , Pain , Coping Skills , Telemedicine/methods , Neoplasms/complications , Neoplasms/therapy , Neoplasms/psychologyABSTRACT
Numerous studies have revealed that the ATP-gated ion channel purinergic 2X7 receptor (P2X7R) plays an important role in tumor progression and the pathogenesis of cancer pain. P2X7R requires activation by extracellular ATP to perform its regulatory role functions. During tumor development or cancer-induced pain, ATP is released from tumor cells or other cells in the tumor microenvironment (such as tumor-associated immune cells), which activates P2X7R, opens ion channels on the cell membrane, affects intracellular molecular metabolism, and regulates the activity of tumor cells. Furthermore, peripheral organs and receptors can be damaged during tumor progression, and P2X7R expression in nerve cells (such as microglia) is significantly upregulated, enhancing sensory afferent information, sensitizing the central nervous system, and inducing or exacerbating pain. These findings reveal that the ATP-P2X7R signaling axis plays a key regulatory role in the pathogenesis of tumors and cancer pain and also has a therapeutic role. Accordingly, in this study, we explored the role of P2X7R in tumors and cancer pain, discussed the pharmacological properties of inhibiting P2X7R activity (such as the use of antagonists) or blocking its expression in the treatment of tumor and cancer pain, and provided an important evidence for the treatment of both in the future.
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OBJECTIVE: There is limited research on neurocognitive outcome and associated risk factors in long-term, adult survivors of childhood acute lymphoblastic leukemia (ALL), without treatment of cranial radiation therapy. Moreover, the impact of fatigue severity and pain interference on neurocognition has received little attention. In this cross-sectional study, we examined neurocognitive outcome and associated factors in this population. METHOD: Intellectual abilities, verbal learning/memory, processing speed, attention, and executive functions were compared to normative means/medians with one sample t tests or Wilcoxon signed-rank tests. Associations with risk factors, fatigue severity, and pain interference were analyzed with linear regressions. RESULTS: Long-term, adult survivors of childhood ALL (N = 53, 51% females, mean age = 24.4 years, SD = 4.4, mean = 14.7 years post-diagnosis, SD = 3.4) demonstrated above average intellectual abilities, but performed below average in attention, inhibition, processing speed, and shifting (p < 0.001). Executive functioning complaints were significantly higher than normative means, and positively associated with fatigue (p < 0.001). There was no interaction between sex and fatigue and no neurocognitive impairments were associated with pain interference, risk group, age at diagnosis, or sex. CONCLUSIONS: Long-term, adult survivors of ALL treated without cranial radiation therapy, demonstrate domain-specific performance-based neurocognitive impairments. However, continued research on the neurocognitive outcome in this population as they age will be important in the coming years. Executive functioning complaints were frequently in the clinical range, and often accompanied by fatigue. This suggests a need for cognitive rehabilitation programs.
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PURPOSE OF REVIEW: The goal of this review is to summarize updates to the broad array of complementary therapies available for cancer pain. This paper will serve as a reference for clinicians managing pain in cancer patients. RECENT FINDINGS: Patients are embracing integrative therapies in growing numbers; clinicians must be prepared to incorporate these therapies into patients' existing treatment regimens. This requires knowledge regarding risks, benefits, and potential interactions with existing cancer therapies. Integrative cancer pain management strategies have shown promise, with several proven effective for the management of cancer pain. Energy therapies, including acupuncture, and biologicals and nutraceuticals including overall diet and vitamin D, have the highest level of evidence for efficacy. The remaining therapies discussed in this chapter may be beneficial for patients on a case-by-case basis; risks and benefits of each individual therapy as described in the text must be further assessed in future rigorous trials to further clarify the role of these complementary therapies in cancer pain management.
Subject(s)
Cancer Pain , Complementary Therapies , Pain Management , Humans , Cancer Pain/therapy , Pain Management/methods , Complementary Therapies/methods , Neoplasms/complications , Neoplasms/therapy , Integrative Medicine/methodsABSTRACT
OPINION STATEMENT: 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.
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BACKGROUND: Opioid tapering and discontinuation have increased in recent years with the implementation of national prescribing guidelines. This study aimed to examine the relationship between opioid tapering velocity and mental health crisis events in older Medicare beneficiaries. METHODS: A nested case-control study was conducted using the 2012-2018, 5% national Medicare claims data. Older adults with chronic non-cancer pain (CNCP) who were receiving long-term opioid therapy (LTOT) were included in the study. Cases were defined as individuals experiencing mental health crisis events; controls were identified using incidence density sampling. The opioid tapering velocity was measured in the 120-day hazard period that yielded a monthly percentage of dose change. Conditional logistic regression was used to assess the relationship of interest. RESULTS: A total of 42 091 older adults with CNCP were eligible for the study. Cases (n = 952) were matched with controls in a 1:2 ratio based on age (±1 year) and time of cohort entry (±30 days). A higher percentage of controls (67.65%) were on steady dose compared with cases (59.03%). In the adjusted model, tapering (aOR = 1.36; 95% CI: 1.02-1.83), rapid tapering (aOR = 1.45; 95% CI: 1.11-1.91), and dose escalation (aOR = 1.78; 95% CI: 1.32-2.39) were significantly associated with the mental health crisis, compared with steady dose. CONCLUSION: Both opioid tapering and dose escalation are associated with mental health crisis events. Patient-driven and gradual dose tapering, as recommended by prescribing guidelines, should be promoted to prevent mental health crisis events among older adults on LTOT.
Subject(s)
Analgesics, Opioid , Chronic Pain , Mental Disorders , Aged , Humans , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Case-Control Studies , Chronic Pain/drug therapy , Chronic Pain/epidemiology , Medicare , United States/epidemiology , Mental Disorders/epidemiologyABSTRACT
PURPOSE: Data indicates that clinicians might be under-prescribing opioids for patients with chronic cancer pain, and this could impact adequate pain management. Few studies have sought to understand healthcare provider (HCP) perceptions and practices regarding the prescription of opioids for chronic cancer pain. We assessed HCP perceptions and practices regarding opioid prescription for patients with chronic cancer pain since the onset of the COVID-19 pandemic. METHODS: An anonymous cross-sectional survey was conducted among 186 HCPs who attended an opioid educational event in April 2021 and 2022. RESULTS: Sixty-one out of 143 (44%) opioid prescribers reported reluctance to prescribe opioids for chronic cancer pain. In a multivariate logistic model, younger participants (log OR - 0.04, 95% CI - 0.085, - 0.004; p = 0.033) and pain medicine clinicians (log OR - 1.89, CI - 3.931, - 0.286; p = 0.034) were less reluctant, whereas providers who worry about non-medical opioid use were more reluctant to prescribe opioids (log OR 1.58 95% CI 0.77-2.43; p < 0.001). Fifty-three out of 143 (37%) prescribers had experienced increased challenges regarding opioid dispensing at pharmacies, and 84/179 (47%) of all respondents reported similar experience by their patients. Fifty-four out of 178(30%) were aware of opioid-related harmful incidents to patients or their families, including incidents attributed to opioid misuse by a household or family member. CONCLUSION: A considerable number of opioid prescribers were reluctant to prescribe opioids for patients with chronic cancer pain. Many reported challenges regarding dispensing of opioids at the pharmacies. These may be unintended consequences of policies to address the opioid crisis. Future measures should focus on addressing regulatory barriers without undermining the gains already made to combat the opioid crisis.
Subject(s)
Cancer Pain , Chronic Pain , Neoplasms , Opioid-Related Disorders , Humans , Analgesics, Opioid/therapeutic use , Cancer Pain/drug therapy , Cross-Sectional Studies , Pandemics , Neoplasms/complications , Chronic Pain/drug therapy , Health PersonnelABSTRACT
PURPOSE: Physical activity can provide analgesic benefit but its effect on cancer-related pain is unclear. This review synthesised and appraised the evidence for the effect of physical activity on pain in people living with or beyond cancer. METHODS: A systematic search of Ovid Medline and Embase was performed to identify randomised controlled trials (RCTs), randomised cross-over studies (RXTs), and prospective observational studies that examined physical activity and pain outcomes in adults living with or beyond cancer. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to assess evidence quality. RESULTS: One hundred twenty-one studies (n = 13,806), including 102 RCTs, 6 RXTs, and 13 observational studies, met the criteria for inclusion. Meta-analyses of RCTs identified a decrease in pain intensity (n = 3734; standardised mean difference (SMD) - 0.30; 95% confidence interval (CI) - 0.45, - 0.15) and bodily pain (n = 1170; SMD 0.28; 95% CI 0.01, 0.56) but not pain interference (n = 207; SMD - 0.13, 95% CI - 0.42, 0.15) following physical activity interventions. Individual studies also identified a reduction in pain sensitivity but not analgesic use, although meta-analysis was not possible for these outcomes. High heterogeneity between studies, low certainty in some effect estimates, and possible publication bias meant that evidence quality was graded as very low to low. CONCLUSION: Physical activity may decrease pain in people living with and beyond cancer; however, high heterogeneity limits the ability to generalise this finding to all people with cancer or to specific types of cancer-related pain.