Transdermal Opioids and the Quality of Life of the Cancer Patient: A Systematic Literature Review.

OBJECTIVE: This systematic literature review aims to evaluate the effectiveness of transdermal opioids in managing cancer pain and their impact on the quality of life (QoL) of patients. DATA SOURCES: A systematic literature review conducted following the PRISMA protocol, focusing on randomized clinical trials found in the Lilacs, Embase, PubMed, and SciELO databases over the last 20 years. STUDY SELECTION AND DATA EXTRACTION: We included randomized clinical trials, published in English, Portuguese, or Spanish, which assessed the impact of transdermal opioids on the QoL. Data extraction was facilitated using the Rayyan app. DATA SYNTHESIS: Six articles meeting the inclusion and exclusion criteria were analyzed. These studies covered a population ranging from 24 to 422 cancer patients experiencing moderate to severe pain. The risk of bias was assessed in each study, generally being categorized as uncertain or high. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The findings indicate that the analgesic effectiveness and side effects of transdermal formulations (specifically buprenorphine and fentanyl) for managing moderate to severe cancer pain are comparable to, or in some cases superior to, those of oral opioids traditionally employed. CONCLUSIONS: Transdermal therapy was suggested to have several advantages over oral opioid therapy in enhancing cancer patients' QoL. These benefits span various dimensions, including pain management, physical functioning, mental health, vitality, overall patient improvement, anger/aversion, strength/activity, general QoL, cognitive and emotional functions, fatigue, and insomnia.

Optimizing cancer pain management in resource-limited settings.

PURPOSE: Adequate cancer pain management (CPM) is challenging in resource-limited settings, where current international guideline recommendations are difficult to implement owing to constraints such as inadequate availability and accessibility of opioids, limited awareness of appropriate opioid use among patients and clinicians, and lack of guidance on how to translate the best evidence into clinical practice. The multinational and multidisciplinary CAncer Pain managEment in Resource-limited settings (CAPER) Working Group proposes a two-step initiative to bridge clinical practice gaps in CPM in resource-limited settings. METHODS: A thorough review of the literature, a steering committee meeting in February 2017, and post-meeting teleconference discussions contributed to the development of this initiative. As a first step, we developed practical evidence-based CPM algorithms to support healthcare providers (HCPs) in tailoring treatment according to availability of and access to resources. The second part of the initiative proposes a framework to support an effective implementation of the CPM algorithms that includes an educational program, a pilot implementation, and an advocacy plan. RESULTS: We developed CPM algorithms for first-line use, breakthrough cancer pain, opioid rotation, and refractory cancer pain based on the National Comprehensive Cancer Network guidelines and expert consensus. Our proposed educational program emphasizes the practical elements and illustrates how HCPs can provide optimal CPM according to evidence-based guidelines despite varied resource limitations. Pilot studies are proposed to demonstrate the effectiveness of the algorithms and the educational program, as well as for providing evidence to support a draft advocacy document, to lobby policymakers to improve availability and accessibility of analgesics in resource-limited settings. CONCLUSIONS: These practical evidence-informed algorithms and the implementation framework represent the first multinational step towards achieving optimal CPM in resource-limited settings.

Use of Opioids in Latin America: The Need of an Evidence-Based Change.

OBJECTIVE: The subject of this publication has been focused on local considerations for facilitating regional best practice, including identifying and uniformly adopting the most relevant international guidelines on opioid use (OU) in chronic pain management. DESIGN AND SETTING: The Change Pain Latin America (CPLA) Advisory Panel conducted a comprehensive, robust, and critical analysis of published national and international reviews and guidelines of OU, considering those most appropriate for Latin America. METHODS: A PubMed search was conducted using the terms "opioid," "chronic," and "pain" and then refined using the filters "practice guidelines" and "within the last 5 years" (2007-2012). Once the publications were identified, they were selected using five key criteria: "Evidence based," "Comprehensive," "From a well-recognized source," "Current publications," and "Based on best practice" and then critically analyzed considering 10 key criteria for determining the most relevant guidelines to be applied in Latin America. RESULTS: The initial PubMed search identified 177 reviews and guidelines, which was reduced to 16 articles using the five preliminary criteria. After a secondary analysis according to the 10 key criteria specific to OU in Latin America, 10 publications were selected for critical review and discussion. CONCLUSIONS: The CPLA advisory panel considered the "Safe and effective use of opioids for chronic non-cancer pain" (published in 2010 by the NOUGG of Canada) to be valid, relevant to Latin America, practical, evidence-based, concise, unambiguous, and sufficiently educational to provide clear instruction on OU and pain management and, thus, recommended for uniform adoption across the Latin America region.

Cannabinoid products for pain management: recommendations from the São Paulo State Society of Anesthesiology.

There is growing interest in using cannabinoids across various clinical scenarios, including pain medicine, leading to the disregard of regulatory protocols in some countries. Legislation has been implemented in Brazil, specifically in the state of São Paulo, permitting the distribution of cannabinoid products by health authorities for clinical purposes, free of charge for patients, upon professional prescription. Thus, it is imperative to assess the existing evidence regarding the efficacy and safety of these products in pain management. In light of this, the São Paulo State Society of Anesthesiology (SAESP) established a task force to conduct a narrative review on the topic using the Delphi method, requiring a minimum agreement of 60% among panelists. The study concluded that cannabinoid products could potentially serve as adjuncts in pain management but stressed the importance of judicious prescription. Nevertheless, this review advises against their use for acute pain and cancer-related pain. In other clinical scenarios, established treatments should take precedence, particularly when clinical protocols are available, such as in neuropathic pain. Only patients exhibiting poor therapeutic responses to established protocols or demonstrating intolerance to recommended management may be considered as potential candidates for cannabinoids, which should be prescribed by physicians experienced in handling these substances. Special attention should be given to individual patient characteristics and the likelihood of drug interactions.

Latin American and Caribbean consensus on noninvasive central nervous system neuromodulation for chronic pain management (LAC2-NIN-CP).

INTRODUCTION: Chronic pain (CP) is highly prevalent and generally undertreated health condition. Noninvasive brain stimulation may contribute to decrease pain intensity and influence other aspects related to CP. OBJECTIVE: To provide consensus-based recommendations for the use of noninvasive brain stimulation in clinical practice. METHODS: Systematic review of the literature searching for randomized clinical trials followed by consensus panel. Recommendations also involved a cost-estimation study. RESULTS: The systematic review wielded 24 transcranial direct current stimulation (tDCS) and 22 repetitive transcranial magnetic stimulation (rTMS) studies. The following recommendations were provided: (1) Level A for anodal tDCS over the primary motor cortex (M1) in fibromyalgia, and level B for peripheral neuropathic pain, abdominal pain, and migraine; bifrontal (F3/F4) tDCS and M1 high-definition (HD)-tDCS for fibromyalgia; Oz/Cz tDCS for migraine and for secondary benefits such as improvement in quality of life, decrease in anxiety, and increase in pressure pain threshold; (2) level A recommendation for high-frequency (HF) rTMS over M1 for fibromyalgia and neuropathic pain, and level B for myofascial or musculoskeletal pain, complex regional pain syndrome, and migraine; (3) level A recommendation against the use of anodal M1 tDCS for low back pain; and (4) level B recommendation against the use of HF rTMS over the left dorsolateral prefrontal cortex in the control of pain. CONCLUSION: Transcranial DCS and rTMS are recommended techniques to be used in the control of CP conditions, with low to moderate analgesic effects, and no severe adverse events. These recommendations are based on a systematic review of the literature and a consensus made by experts in the field. Readers should use it as part of the resources available to decision-making.

Neuropathic pain--neurochemical aspects.

BACKGROUND AND OBJECTIVES: Neuropathic pain is caused by damage or inflammation of the nervous system. It is a complex syndrome and its biological mechanisms, involving inflammatory and immunologic theories, are not clear. The objective of this review was to describe the main biologic factors associated with neuropathic pain, making a logical association between hypotheses suggested in the literature. CONTENTS: The main neuromediators, ion channels, and cells, including cells in the nervous system involved in neuronal excitation are described, and the possible activation sequence or interaction among those agents in the neoplastic change secondary to nerve damage are emphasized. CONCLUSIONS: It was possible to conclude that the advances on the knowledge of the pathophysiology of neuropathic pain can determine new pharmacologic approaches for this syndrome.

Undertreatment of pain and low use of opioids in Latin America.

Pain is highly prevalent among the adult Latin American population. However, many patients with moderate to severe pain do not have access to effective pain management with opioids due to limited access to healthcare, overuse of nonopioid analgesics, regulatory barriers and lack of appropriate information about opioids. There is scarce training on use of opioids among physicians and other healthcare providers, which leads to misconceptions, mainly related to a fear of prescribing opioids. Although opioids are safe and effective drugs for the treatment of moderate to severe chronic pain, the use of opioids in Latin American nations is clearly below standards compared with developed countries.

[Optimizing post-operative pain management in Latin America]. / Aprimorar o controle da dor no pós­operatório na América Latina.

Post-operative pain management is a significant problem in clinical practice in Latin America. Insufficient or inappropriate pain management is in large part due to insufficient knowledge, attitudes and education, and poor communications at various levels. In addition, the lack of awareness of the availability and importance of clear policies and guidelines for recording pain intensity, the use of specific analgesics and the proper approach to patient education have led to the consistent under-treatment of pain management in the region. However, these problems are not insurmountable and can be addressed at both the provider and patient level. Robust policies and guidelines can help insure continuity of care and reduce unnecessary variations in practice. The objective of this paper is to call attention to the problems associated with Acute Post-Operative Pain (APOP) and to suggest recommendations for their solutions in Latin America. A group of experts on anesthesiology, surgery and pain developed recommendations that will lead to more efficient and effective pain management. It will be necessary to change the knowledge and behavior of health professionals and patients, and to obtain a commitment of policy makers. Success will depend on a positive attitude and the commitment of each party through the development of policies, programs and the promotion of a more efficient and effective system for the delivery of APOP services as recommended by the authors of this paper. The writing group believes that implementation of these recommendations should significantly enhance efficient and effective post-operative pain management in Latin America.

[Postoperative persistent chronic pain: what do we know about prevention, risk factors, and treatment]. / Dor crônica persistente pós-operatória: o que sabemos sobre prevenção, fatores de risco e tratamento?

BACKGROUND AND OBJECTIVES: Postoperative persistent chronic pain (POCP) is a serious health problem, disabling, undermining the quality of life of affected patients. Although more studies and research have addressed the possible mechanisms of the evolution from acute pain to chronic postoperatively, there are still no consistent data about the risk factors and prevention. This article aims to bring what is in the panorama of the current literature available. CONTENT: This review describes the definition, risk factors, and mechanisms of POCD, its prevention and treatment. The main drugs and techniques are exposed comprehensively. CONCLUSION: Postoperative persistent chronic pain is a complex and still unclear etiology entity, which interferes heavily in the life of the subject. Neuropathic pain resulting from surgical trauma is still the most common expression of this entity. Techniques to prevent nerve injury are recommended and should be used whenever possible. Despite efforts to understand and select risk patients, the management and prevention of this syndrome remain challenging and inappropriate.

Postoperative persistent chronic pain: what do we know about prevention, risk factors, and treatment.

BACKGROUND AND OBJECTIVES: Postoperative persistent chronic pain (POCP) is a serious health problem, disabling, undermining the quality of life of affected patients. Although more studies and research have addressed the possible mechanisms of the evolution from acute pain to chronic postoperatively, there are still no consistent data about the risk factors and prevention. This article aims to bring what is in the panorama of the current literature available. CONTENT: This review describes the definition, risk factors, and mechanisms of POCD, its prevention and treatment. The main drugs and techniques are exposed comprehensively. CONCLUSION: Postoperative persistent chronic pain is a complex and still unclear etiology entity, which interferes heavily in the life of the subject. Neuropathic pain resulting from surgical trauma is still the most common expression of this entity. Techniques to prevent nerve injury are recommended and should be used whenever possible. Despite efforts to understand and select risk patients, the management and prevention of this syndrome remain challenging and inappropriate.

Selenium and Zinc Status in Chronic Myofascial Pain: Serum and Erythrocyte Concentrations and Food Intake.

INTRODUCTION: Nutritional disorders have been reported to be important causal factors that can intensify or cause a painful response in individuals with chronic musculoskeletal pain. AIM: To assess the habitual intake of and the serum and erythrocyte levels of selenium and zinc in patients with chronic myofascial pain. MATERIALS AND METHODS: A case-control study of 31 patients with chronic myofascial pain (group I) and 31 subjects without pain (group II). Dietary record in five days for assessing food intake were used. The serum and erythrocyte concentrations of selenium and zinc were analyzed using an atomic absorption spectrophotometry. Pain intensity was assessed using a visual analog scale. RESULTS: The group of patients with chronic myofascial pain, compared with the control group, showed a lower erythrocyte concentration of selenium (79.46 ± 19.79 µg/L vs. 90.80 ± 23.12 µg/L; p = 0.041) and zinc (30.56 ± 7.74 µgZn/gHb vs. 38.48 ± 14.86 µgZn/gHb, respectively; p = 0.004). In this study, a compromised food intake of zinc was observed in the majority of the subjects in both groups. The selenium intake was considered to be safe in 80% of the subjects in both groups; however, the likelihood of inadequate intake of this mineral was twice as high in group I (49.5% vs. 24.4%, respectively). In the logistic regression analysis, the erythrocyte concentration of zinc was associated with the presence of pain. In each additional 1 mg of Zn2+ per gram of hemoglobin, a reduction of 12.5% was observed in the risk of the individual having chronic myofascial pain (B = -0.133; adjusted OR = 0.875, 95% CI = 0.803 to 0.954, Wald = 9.187, standard error = 0.044, p = 0.002). Physical inactivity and obesity were noted more commonly in group I compared with the control group. CONCLUSION: In this study, patients with chronic myofascial pain showed lower intracellular stores of zinc and selenium and inadequate food intake of these nutrients.

[The analgesic effect of intravenous lidocaine in the treatment of chronic pain: a literature review]. / A ação analgésica da lidocaína intravenosa no tratamento da dor crônica: uma revisão de literatura.

BACKGROUND: Pain is a public health problem, greatly impairing quality of life. Almost 80% of patients with chronic pain reported that their pain interferes with activities of daily living, and two thirds reported that the pain causes negative impact on their personal relationships. The physical and functional disability, whether temporary or permanent, compromises the professional activity and causes work absenteeism, increasing costs of health systems. OBJECTIVES: The aim of this review is to analyze, based on the literature, the analgesic effect of lidocaine administered intravenously for the treatment of chronic pain and to evaluate the reduction of pain intensity in patients with chronic pain, focusing on musculoskeletal and neuropathic etiology. METHODOLOGY: The method used was a review of the literature, consisting in searching the scientific literature on the efficacy of intravenous lidocaine infusion in the treatment of patients with chronic pain. CONTENT: Of the 19 studies reviewed, 12 had results that confirm the analgesic effect of intravenous lidocaine in patients with chronic pain. Most authors used doses of 5mg/kg infused for 30minutes or more, producing significant analgesia with variable duration (minutes to weeks). CONCLUSIONS: Based on the literature review, it is not possible to uniformly specify the most effective and safe dose of lidocaine administered intravenously for the treatment of neuropathic or musculoskeletal pain. As for effectiveness, the intravenous infusion of lidocaine as an alternative for the treatment of chronic pain of various etiologies seems very promising, but further studies need to be conducted.

Chronic pain: cytokines, lymphocytes and chemokines.

Chronic pain is a debilitating condition and, in most cases, difficult to treat. A prominent example of this is neuropathic pain. Understanding pathophysiological mechanisms of pain and, therefore, making this knowledge into an effective treatment is still a challenge to experts. Pain can now be considered as a neuro-immune disorder, since recent data indicate critical involvement of innate and adaptive immune responses following injury, and this interaction plays an important role in the onset and perpetuation of chronic pain. The aim of this article is to review the relationship between immune system and chronic pain, especially about neuropathic pain, and focusing on cytokines, chemokines and lymphocytes.

Clinical evaluation and prevalence of fibromyalgia in hepatitis C patients / Avaliação clínica e prevalência de fibromialgia em pacientes portadores de hepatite C

ABSTRACT BACKGROUND AND OBJECTIVES: The worldwide distribution and etiology of fibromyalgia are poorly understood. It is believed that different factors are involved, such as hepatitis C virus infection. The aim of this study was to estimate the prevalence of fibromyalgia in hepatitis C virus infected patients, trying to identify the occurrence of liver injury, extrahepatic clinical manifestations, anxiety, depression, and the impact on the quality of life. METHODS: This is a cross-sectional study of patients (n=118) with hepatitis C virus infection who were compared with a group of clinically stable patients not infected with the hepatitis C virus (n=118). The Anxiety and Depression Questionnaire was applied, and for those diagnosed with fibromyalgia, the Fibromyalgia Impact Questionnaire. Liver biopsies were analyzed according to the METAVIR classification. The Schirmer test was performed to investigate abnormal tear production in the studied patients. Data analysis was performed using the Statistical Package for Social Sciences (SPSS) software, v.10.0. RESULTS: The prevalence of fibromyalgia in infected patients was 7.6%. In patients infected with fibromyalgia, a significant prevalence of anxiety and depression was observed. Fibromyalgia Impact Questionnaire scores were higher in infected patients with fibromyalgia. When comparing the complementary tests in infected patients with and without fibromyalgia, no significant differences were found for the Schirmer test, viral genotype, and degree of fibrosis and liver inflammation. CONCLUSION: In females, there was a positive relationship between hepatitis C virus infection, fibromyalgia, and extrahepatic symptoms, which translates into a higher prevalence of anxiety and depression and impaired quality of life.

RESUMO JUSTIFICATIVA E OBJETIVOS: A fibromialgia tem distribuição mundial e etiologia pouco comprendida. Acredita-se no envolvimento de diferentes fatores, como a infecção pelo vírus da hepatite C. O objetivo deste estudo foi estimar a prevalência de fibromialgia em pacientes infectados pelo vírus da hepatite C, procurando identificar a ocorrência de lesão hepática, manifestações clínicas extra-hepáticas, ansiedade, depressão e o impacto na qualidade de vida. MÉTODOS: Trata-se de um estudo de corte transversal com pacientes (n=118) portadores de infecção pelo vírus da hepatite C que foram comparados a um grupo composto de pacientes clinicamente estáveis e não infectados pelo vírus da hepatite C (n=118). Foi aplicado o Questionário de Ansiedade e Depressão, e para os que obtivessem o diagnóstico de fibromialgia, o Questionário de Impacto da Fibromialgia. As biopsias hepáticas foram analisadas de acordo com a classificação METAVIR. Foi realizado o teste de Schirmer para a pesquisa de lacrimejamento anormal nos pacientes estudados. A análise dos dados foi realizada através do programa Statistical Package for Social Sciences (SPSS) v.10.0. RESULTADOS: A prevalência de fibromialgia em pacientes infectados foi de 7,6%. Nos pacientes infectados com fibromialgia observou-se prevalência significativa de ansiedade e depressão. A pontuação do Questionário de Impacto da Fibromialgia foi maior nos pacientes infectados e com fibromialgia. Quando se relacionou os exames complementares em infectados com e sem fibromialgia, não foram constatadas diferenças significativas para o teste de Schirmer, genótipo viral e grau de fibrose e inflamação hepática. CONCLUSÃO: Nos indivíduos do sexo feminino, observou-se uma relação positiva entre a infecção pelo vírus da hepatite C, fibromialgia e sintomas extra-hepáticos, que se traduz em maior prevalência de ansiedade e depressão e em comprometimento na qualidade de vida.