Chronic Cancer Pain Research Articles

Cancer-Related Pain: Inside a New Dynamic Personalized Approach. A Narrative Review

Chronic cancer-related pain, according to the latest International Classification of Diseases (ICD-11), is defined as “chronic pain caused by the primary cancer itself or metastases (chronic cancer pain) or its treatment (chronic post-cancer treatment pain)”

Depression and Long-Term Prescription Opioid Use and Opioid Use Disorder: Implications for Pain Management in Cancer.

Opinion statementPreventing depression in cancer patients on long-term opioid therapy should begin with depression screening before opioid initiation and repeated screening during treatment. In weighing the high morbidity of depression and opioid use disorder in patients with chronic cancer pain against a dearth of evidence-based therapies studied in this population, patients and clinicians are left to choose among imperfect but necessary treatment options. When possible, we advise engaging psychiatric and pain/palliative specialists through collaborative care models and recommending mindfulness and psychotherapy to all patients with significant depression alongside cancer pain. Medications for depression should be reserved for moderate to severe symptoms. We recommend escitalopram/citalopram or sertraline among selective serotonin reuptake inhibitors (SSRIs), or the serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine, venlafaxine, or desvenlafaxine if patients have a significant component of neuropathic pain or fibromyalgia. Tricyclic antidepressants (TCAs) (consider nortriptyline or desipramine, which have better anticholinergic profiles) should be considered for patients who do not respond to or tolerate SSRI/SNRIs. Existing evidence is inadequate to definitively recommend methylphenidate or novel agents, such as ketamine or psilocybin, as adjunctive treatments for cancer-related depression and pain. Physicians who treat patients with cancer pain should utilize universal precautions to limit the risk of non-medical opioid use (non-medical opioid use). Patients should be screened for non-medical opioid use behaviors at initial consultation and at regular intervals during treatment using a non-judgmental approach that reduces stigma. Co-management with an addiction specialist may be indicated for patients at high risk of non-medical opioid use and opioid use disorder. Buprenorphine and methadone are indicated for the treatment of opioid use disorder, and while they have not been systematically studied for treatment of opioid use disorder in patients with cancer pain, they do provide analgesia for cancer pain. While an interdisciplinary team approach to manage psychological stress may be beneficial, this may not be possible for patients treated outside of comprehensive cancer centers.

Novel role of the Mu-opioid receptor in pancreatic cancer: potential link between opioid use and cancer progression.

Opioids are the most popular drugs for both acute and chronic pain management. The G protein-coupled mu-opioid receptor (MOR) is the therapeutic target for most clinically used opioids, including morphine. A mounting number of publications suggest a relationship between the MOR and possible cancer progression and recurrence extending to managing chronic cancer pain. In this study, we studied the possible link between opioid use and pancreatic cancer (PC) progression. We found increased MOR expression in murine and human PC cell lines, human PC-derived organoids, and in the undifferentiated or poorly differentiated areas of surgically resected PC tissues. Direct stimulation of MOR by morphine (MOR agonist) caused a significant dose-dependent increase in proliferation, invasion, and levels of stemness markers in PC cells. In a co-culture system, MOR stimulation of macrophages also resulted in increased proliferation of PC cells. MOR overexpression increased proliferation and cancer stemness, whereas knock-down of MOR followed opposite results in the PC cells. Morphine induced chemoresistance to conventional chemotherapeutic agents used for PC treatment. Overall, our results suggest that MOR is expressed in pancreatic cancer and may be involved in tumor progression and chemoresistance.

A scoping review of outpatient interventions to support the reduction of prescription opioid medication for chronic non cancer pain.

Prescription opioid use is a global health issue. Previous systematic reviews have not identified that any specific intervention supports prescription opioid reduction effectively. In keeping with the nature of a scoping review, this review details an overview of the existing literature on this topic, with quality of evidence being discussed rather than formally analysed. This review aimed to examine and describe outpatient interventions that support the reduction of prescription opioid medication for chronic non cancer pain. Abstracts were reviewed against the inclusion criteria of outpatient clinical interventions, for the purpose of prescription opioid dose reduction, offered to adults with CNCP. Following a structured review approach an electronic database search, of Medline, Embase, Cochrane, Cinahl, and Proquest and grey literature was undertaken. Search results were screened by title for relevance. Two reviewers adhering to the PRISMA-ScR checklist charted and assessed studies for quality using Critical Appraisal Skills Programme checklist assessment tools. Extracted data were collated and synthesised for presentation as a tabular and narrative review. From the initial search of 5089 papers, 19 underwent full-text review and quality appraisal. A variety of interventions were described to support reduction in prescription opioid use, however only one study of at least fair quality was able to demonstrate a demonstrated a statistically significant benefit in reducing measured opioid dose compared with a control group. Interventions were implemented in both specialist pain services and in primary care with multidisciplinary and interdisciplinary clinician care. Barriers and facilitators were observed in both settings. Further rigorous research needs to be conducted to conclusively answer the question of what outpatient interventions support opioid reduction in chronic non cancer pain. This scoping review is the first step of inquiry in the development of a nursing intervention to support reduction of prescription opioids.

LncRNA NONRATT009773.2 promotes bone cancer pain progression through the miR-708-5p/CXCL13 axis.

Bone cancer pain (BCP) is the most frequently observed chronic cancer pain, and its development remains largely unexplored. Dysregulation of non-coding RNAs greatly contributes to the pathogenesis of BCP. In the present study, we found a new long noncoding RNA (lncRNA), NONRATT009773.2, and investigated its role in the spinal cord of BCP rats. Our results showed that NONRATT009773.2 was significantly up-regulated in BCP model rats, whereas depletion of NONRATT009773.2 attenuated BCP. In contrast, overexpression of NONRATT009773.2 triggered pain-like symptoms in normal animals. Moreover, NONRATT009773.2 functioned as a microRNA (miRNA) sponge to absorb miR-708-5p and up-regulated miRNA downstream target CXCL13, which plays fundamental roles in the initiation and maintenance of neuroinflammation and hyperalgesia. Collectively, our current findings indicated that NONRATT009773.2 could be employed as a new therapeutic target for BCP.

The Assessment and Management of Acute and Chronic Cancer Pain Syndromes.

To provide an overview of the most common acute and chronic cancer-related pain syndromes along with their assessment and management. Data sources include peer-reviewed articles, textbooks, and the internet. Various pain syndromes occur throughout the cancer trajectory. Assessing and managing these syndromes, up to years' after treatment, can assure that comfort is provided from diagnosis throughout survivorship. Oncology nurses are essential in assessing and managing acute and chronic cancer-related pain syndromes. Nurses have both a professional and an ethical responsibility to understand these syndromes and to provide optimal pain management.

Effectiveness of different acupuncture therapies for chronic cancer pain: A protocol for systematic review and Bayesian network meta-analysis.

Background:Pain is a common and distressing symptom experienced by cancer patients. Previous research found acupuncture was associated with significant reductions in pain intensity and opioid use. Acupuncture therapies are various, and the difference in efficacy and safety has never been assessed. This paper aims to assess and rank the effectiveness of the different acupuncture methods and provide an acupuncture treatment guideline for relieving chronic pain in cancer survivors.Methods:Four English databases (PubMed, Embase, Cochrane library, and Web of Science) and 4 Chinese databases (China National Knowledge Infrastructure, Wanfang Data, and Chinese Biomedical Literature Database) will be searched for randomized controlled trials (RCTs) published from the database inception to November 30, 2021. The primary outcomes will be patient-reported pain intensity measured by the Brief Pain Inventory, Visual Analog Scale, Verbal Rating Scale, Numerical Rating Scale, and other valid outcome measures. The Grading of Recommendations Assessment, and Development and Evaluation System will evaluate the quality of evidence. Bayesian network meta-analysis will be performed in WinBUGS V.1.4.3 to determine the comparative effectiveness of the acupuncture therapies.Results:This study will quantify the effectiveness of each acupuncture intervention for chronic cancer pain with pain scores and the use of analgesics. The adverse events of acupuncture treatment for cancer pain will also be reported.Conclusion:The conclusion of our study will help physicians and patients choose suitable acupuncture methods to manage cancer pain.

Chronic pain, prescribed opioids and overdose risk: a qualitative exploration of the views of affected individuals and family members

It has been estimated that chronic non cancer pain (CNCP) affects more than 30% of people worldwide. Correspondingly, prescriptions for individuals experiencing CNCP have increased in recent years. While opioids can minimize pain, they also pose a risk of overdose. In 2019 in Scotland, prescription analgesics contributed to, or were implicated in, approximately 19% of drug related deaths. The experiences of those prescribed opioids for CNCP and family members, particularly their perceptions of overdose risk, are under-explored in the literature. This study aimed to address this gap by exploring how individuals and family members perceive the issue of overdose in relation to opioid analgesics, and their views of overdose prevention and potential interventions. Lived experiences from 12 individuals and family members living in Scotland were shared via in-depth qualitative interviews and analysed using NVivo and Framework. Coding was iterative and deductive. Analysis generated five themes: (1) living with pain and experiencing stigma; (2) taking more medication than prescribed; (3) side effects of medication; (4) overdose risk and prevention: the role of prescribers; and (5) attitudes towards naloxone to address overdose risk. Study findings have implications for the development of interventions and broader responses to reduce overdose risk among this group.

Analgesic Opioid Ligand Discovery Based on Nonmorphinan Scaffolds Derived from Natural Sources.

Strong opioid analgesics, including morphine, are the mainstays for treating moderate to severe acute pain and alleviating chronic cancer pain. However, opioid-related adverse effects, including nausea or vomiting, sedation, respiratory depression, constipation, pruritus (itch), analgesic tolerance, and addiction and abuse liability, are problematic. In addition, the use of opioids to relieve chronic noncancer pain is controversial due to the "opioid crisis" characterized by opioid misuse or abuse and escalating unintentional death rates due to respiratory depression. Hence, considerable research internationally has been aimed at the "Holy Grail" of the opioid analgesic field, namely the discovery of novel and safer opioid analgesics with improved opioid-related adverse effects. In this Perspective, medicinal chemistry strategies are addressed, where structurally diverse nonmorphinan-based opioid ligands derived from natural sources were deployed as lead molecules. The current state of play, clinical or experimental status, and novel opioid ligand discovery approaches are elaborated in the context of retaining analgesia with improved safety and reduced adverse effects, especially addiction liability.

Chronic cancer pain: pathophysiology and ICD-11 classification

Chronic cancer pain is one of the most common symptoms affecting oncology patients and cancer survivors. Epidemiological trends show that its recognition and management are increasingly important. The ICD-11 provides a better analysis of this problem based on the pathophysiological characteristics of cancer-related pain. This article proposes to review the mechanisms of cancer-related pain in relation to this classification.

A Linear Decomposition Approach to Explain Excess Direct Healthcare Expenditures Associated with Pain Among Adults with Osteoarthritis.

Many patients with osteoarthritis experience pain which can lead to higher healthcare expenditures. It is important to understand the factors that drive the excess expenditures associated with pain in osteoarthritis. Cross-sectional. Our study sample consisted of adults (age ⩾ 18 years) from the Medical Expenditure Panel Survey (MEPS, 2018). Adults who were alive during the calendar year and had pain status were included in this study (N = 2804 weighted N = 32.03 million). Osteoarthritis was identified from the medical conditions file and household file. We used multivariable ordinary least squares regression to identify the statistically significant association of pain with direct healthcare expenditures. The Blinder-Oaxaca post-linear decomposition on log-transformed total direct healthcare expenditures was used to estimate the extent to which differences in characteristics contribute to the excess expenditures associated with pain. Adults with osteoarthritis and pain had higher average expenditures ($21 814 vs $10 827, P < .001; 9.318 vs 8.538 in logtransformed expenditures) compared to those without pain. Pooled regression weights explained 62.9% of excess expenditures differences in characteristics between the 2 groups. The 2 main drivers of excess healthcare expenditures among adults with osteoarthritis and pain were (i) comorbidities (diabetes, asthma, chronic obstructive pulmonary disease, depression, heart diseases, cancer, and non-cancer pain conditions and (ii) prescription medications (NSAIDs, opioids, and polypharmacy). Need factors such as comorbid conditions, and prescription treatment explained the excess healthcare expenditures among adults with osteoarthritis and pain. The study findings suggest that reducing polypharmacy and appropriate management of comorbid conditions may be a pathway to reduce excess expenditures among adults with osteoarthritis and pain.

Chronic Pain Treatment for Patients with Vascular Ulcers of the Lower Limbs

Pain is found in 46-84.5% of patients with vascular ulcers of the lower limbs, varying according to the records considered and the etiology of the ulcer. Vascular ulcers associated with arterial insufficiency are generally more painful than vascular ulcers associated with venous insufficiency. An algorithm for the management of chronic cancer pain in patients is provided by the WHO analgesic ladder, which is commonly used by physicians. In clinical practice, the ladder is also applied to chronic non-cancer pain, even though this kind of application is limited by the absence of an evaluation of the pathogenetic mechanisms of pain. The WHO analgesic ladder drives therapy solely depending on the severity and persistence of pain, recommending progressive “step by step” pharmacologic therapy, starting with non-opioid medications (NSAIDs and Paracetamol) for mild pain, followed by mild (e.g. tramadol) and strong opioids (e.g. morphine) for moderate to severe pain. It must be noted that addiction to long-term therapy may occur even with non-opioid drugs. Short-term therapy with opioids has been associated with adverse reactions (nausea, constipation, sleepiness, dizziness and itching) in nearly 50% of the patients. Our revision of the literature on this subject analyzes the issues of analgesic chronic therapy with opioids, providing directions on how to optimize it for patients with chronic pain associated with the presence of vascular ulcers of the legs.

Intrathecal drug delivery for chronic pain management

Intrathecal drug delivery appeared in the early eighties and allows to administer high concentrate analgesic medications in the cerebrospinal fluid with higher efficacy and a limited incidence of systemic side effects. Opioids are still the first line treatment with high-quality evidence for chronic cancer pain, and limited evidence for chronic non-cancer pain, being often considered as a last resort therapy. Device implantation requires a strict patient's selection with a close follow-up in order to adapt therapy, refill the reservoir and detect and prevent potential severe complications.

Role of erector spinae plane block in end-of-life care for a patient with advanced abdominal malignancy

Celiac plexus block (CPB) is the most commonly used intervention in patients suffering from pain related to upper abdominal malignancies. Placing a CPB requires a patient to be placed in a prone position on the operating room table which becomes difficult in many patients with advanced disease and therefore makes it more challenging for the interventional pain physician, simultaneously risky for the patient. In such cases, a more superficial minimally invasive intervention is desirable. The erector spinae plane block (ESPB) is one such intervention that has been used in a large variety of settings and can be used in the abovementioned cases. So far, no reports have emphasized the role of this field block for chronic cancer pain relief in a patient with advanced and progressive malignancy nearing the end of life. We present such a case with end-stage carcinoma gallbladder, in which ESPB was used effectively for providing pain relief during her final days.

Knowledge of opioid-induced respiratory depression among Chinese health care professionals: A cross-sectional study

ObjectiveThe purposes of this study were to measure knowledge about opioid-induced respiratory depression (OIRD) among Chinese health care professionals and explore the associated factors that influence Chinese health care professionals’ knowledge. MethodsA cross-sectional survey was conducted. A convenience sample of 900 Chinese health care professionals from 21 provinces, four municipalities, and four autonomous regions was used. The OIRD knowledge questionnaire, which is a self-designed questionnaire based on evidence, was used to judge the degree of knowledge among Chinese health care professionals according to the accuracy rate. The questionnaire included questions on six dimensions of knowledge. Sociodemographic characteristics were also measured by a multi-item questionnaire. ResultsThe overall accuracy rate on the OIRD knowledge questionnaire for all participants were 64.5% ±10.0% (mean ± SD) with a range from 20% to 100%. According to univariate analysis, Chinese health care professionals’ OIRD knowledge was positively correlated with age, region, profession, hospital level, type of hospitals and departments, education level, years of clinical working, and clinical practice of chronic cancer pain (CP) management. Multiple linear regression analysis showed differences in professions and regions (all P ​< ​0.05). ConclusionsMost Chinese health care professionals had misconceptions about OIRD and lacked relevant knowledge. We should assign importance to developing targeted training programs and exploring feasible and effective training methods.

Animal models and experimental medicine and the Nobel Prize in Physiology or Medicine 2021-TRPV and PIEZO receptors for temperature and touch sensation.

Animal models and experimental medicine and the Nobel Prize in Physiology or Medicine 2021-TRPV and PIEZO receptors for temperature and touch sensation.

Minimally invasive interventional analgesia promotes precise treatment and whole process management of chronic pain diseases

Minimally invasive interventional analgesia technique is one of the core diagnosis and treatment techniques of the pain department. It can diagnose and treat many pain diseases such as chronic musculoskeletal pain, chronic neuropathic pain and chronic cancer pain with less trauma and good effect. With the emergence of new ideas and materials, minimally invasive interventional analgesia will be widely used in the setting of chronic pain diseases, achieve the precise diagnosis and treatment and whole-process management of chronic pain diseases.

Dezocine as a potent analgesic: overview of its pharmacological characterization.

Dezocine, a synthetic opioid, introduced in 1970s as an analgesic, was redeveloped for relieving moderate to severe pain by Yangtze River Pharmaceutical Group in China in 2009. To date, dezocine occupies 45% of China's opioid analgesic market. Along with dezocine being a dominated painkiller, a certain amount of research was conducted to elucidate dezocine's action. In this review we summarize the current knowledge on the receptor, preclinical and clinical pharmacology of dezocine. Briefly, preclinical data show that dezocine is effective under varying pain conditions, particularly chronic neuropathic pain and cancer pain, through activation of opioid receptors, and inhibition of norepinephrine reuptake. Clinical data establish the effectiveness of dezocine either as a primary analgesic for postoperative pain management or a supplement for balanced analgesia. The receptor profile of dezocine is different from known pure μ agonists, and allows it to be used in combination with other opioids for additivity in efficacy or lower incidence of adverse effects.

Decrease in pain perception during acute SARS-CoV-2 infection: a case series.

Many reports have described pain appearance or an increase of chronic pain concomitant to severe acute respiratory syndrome coronavirus 2 infection. Here, we describe the cases of 3 patients with chronic cancer pain, in which COVID-19 was associated with a dramatic reduction or disappearance of pain. Pain reappeared after recovery from COVID-19. Neurological imaging and pathological findings, when available, were inconclusive. To the best of our knowledge, this is the first case series reporting an acute reduction in pain perception in COVID-19. We believe further investigation is mandatory because it could shed new light on the mechanisms of pain perception and modulation.

An Italian Expert Consensus on the Use of Opioids for the Management of Chronic Non-Oncological Pain in Clinical Practice: Focus on Buprenorphine.

PurposeThe aim of the present work was to evaluate the knowledge and prescriptive habits of clinicians involved in the management of chronic non cancer pain (CNCP), with a special focus on the use of opioids.MethodsA Delphi method was used. A Board of specialists elaborated and discussed a series of statements, based on available literature and personal clinical expertise, about particularly controversial topics on pain pathophysiology and treatment. A Panel of experts in the field of pain management, selected by the Board, was invited to vote the proposed statements, indicating the level of agreement on a 5-point Likert scale (1: strongly disagree; 2: disagree; 3: partially agree; 4: agree; 5: strongly agree). The threshold for consensus was set at minimum 66.6% of the number of respondents with a level of agreement ≥4 (Agree or Strongly agree).ResultsThe Board included 5 pain therapists, 1 pharmacologist and 1 methodology expert and drew up a total of 36 statements (for a total of 40 requested answers)”. A total of 100 clinicians were included in the Expert Panel. Respondents were 89 (89%). Consensus was achieved for 32 out of 40 answers. Most of the lack of consensus was recorded for statements regarding opioids use, and resulted from a low level of agreement (3 on the Likert scale), suggesting a neutral position deriving from a lack of knowledge rather than a strong contrary opinion.ConclusionMost of the proposed items reached consensus, suggesting a generally homogeneous approach to CNCP management. However, the lack of consensus recorded for several items regarding opioid use confirms the need to fill important gaps in the knowledge of available agents. A clear explanation of the peculiar pharmacological properties of drugs associated with potential clinical advantages (such as buprenorphine) will help optimize pain treatment in both primary care and hospital settings and improving pain control in CNCP patients.