Pain Management in Patients with Cancer: Focus on Opioid Analgesics

Cancer pain is generally treated with pharmacological measures, relying on using opioids alone or in combination with adjuvant analgesics. Weak opioids are used for mild-to-moderate pain as monotherapy or in a combination with nonopioids. For patients with moderate-to-severe pain, strong opioids are recommended as initial therapy rather than beginning treatment with weak opioids. Adjunctive therapy plays an important role in the treatment of cancer pain not fully responsive to opioids administered alone (ie, neuropathic, bone, and visceral colicky pain). Supportive drugs should be used wisely to prevent and treat opioids’ adverse effects. Understanding the pharmacokinetics, pharmacodynamics, interactions, and cautions with commonly used opioids can help determine appropriate opioid selection for individual cancer patients.     

A Network Meta-Analysis of the Efficacy of Opioid Analgesics for the Management of Breakthrough Cancer Pain Episodes

ContextWith many medications available for the management of breakthrough cancer pain (BTCP), physicians may require additional guidance in selecting an appropriate medication to suit an individual patient's needs.ObjectivesTo identify all the evidence and assess the relative clinical value of currently approved BTCP medications.MethodsFollowing a systematic literature search (2007–2010), the results of 10 randomized controlled trials investigating the effects of BTCP medications (intranasal fentanyl spray [INFS], fentanyl pectin nasal spray, fentanyl sublingual tablets, fentanyl buccal soluble film, fentanyl buccal tablets, oral transmucosal fentanyl citrate, and morphine sulfate immediate release) were synthesized using a network meta-analysis. The main outcome was pain intensity difference (PID) relative to placebo up to 60 minutes after the intake of medication.ResultsINFS, fentanyl pectin nasal spray, fentanyl buccal tablet, and oral transmucosal fentanyl citrate showed greater PIDs relative to placebo than other BTCP medications 15 minutes after intake. All other medications showed greater PIDs relative to placebo at 30 minutes, except morphine sulfate immediate release, which did not show efficacy over placebo until 45 minutes. Only INFS produced clinically meaningful pain relief (absolute PID ≥2) at 15 minutes.ConclusionFrom current evidence, although all BTCP medications provided pain relief within the time frames assessed, transmucosal fentanyl medications achieved a greater level of pain relief in a shorter time frame than placebo or oral morphine.     

Genome-Wide Meta-analysis Identifies Genetic Variants Associated With Glycemic Response to Sulfonylureas

OBJECTIVESulfonylureas, the first available drugs for the management of type 2 diabetes, remain widely prescribed today. However, there exists significant variability in glycemic response to treatment. We aimed to establish heritability of sulfonylurea response and identify genetic variants and interacting treatments associated with HbA_1c reduction.RESEARCH DESIGN AND METHODSAs an initiative of the Metformin Genetics Plus Consortium (MetGen Plus) and the DIabetes REsearCh on patient straTification (DIRECT) consortium, 5,485 White Europeans with type 2 diabetes treated with sulfonylureas were recruited from six referral centers in Europe and North America. We first estimated heritability using the generalized restricted maximum likelihood approach and then undertook genome-wide association studies of glycemic response to sulfonylureas measured as HbA_1c reduction after 12 months of therapy followed by meta-analysis. These results were supported by acute glipizide challenge in humans who were naïve to type 2 diabetes medications, cis expression quantitative trait loci (eQTL), and functional validation in cellular models. Finally, we examined for possible drug-drug-gene interactions.RESULTSAfter establishing that sulfonylurea response is heritable (mean ± SEM 37 ± 11%), we identified two independent loci near the GXYLT1 and SLCO1B1 genes associated with HbA_1c reduction at a genome-wide scale (P < 5 × 10⁻⁸). The C allele at rs1234032, near GXYLT1, was associated with 0.14% (1.5 mmol/mol), P = 2.39 × 10⁻⁸), lower reduction in HbA_1c. Similarly, the C allele was associated with higher glucose trough levels (β = 1.61, P = 0.005) in healthy volunteers in the SUGAR-MGH given glipizide (N = 857). In 3,029 human whole blood samples, the C allele is a cis eQTL for increased expression of GXYLT1 (β = 0.21, P = 2.04 × 10⁻⁵⁸). The C allele of rs10770791, in an intronic region of SLCO1B1, was associated with 0.11% (1.2 mmol/mol) greater reduction in HbA_1c (P = 4.80 × 10⁻⁸). In 1,183 human liver samples, the C allele at rs10770791 is a cis eQTL for reduced SLCO1B1 expression (P = 1.61 × 10⁻⁷), which, together with functional studies in cells expressing SLCO1B1, supports a key role for hepatic SLCO1B1 (encoding OATP1B1) in regulation of sulfonylurea transport. Further, a significant interaction between statin use and SLCO1B1 genotype was observed (P = 0.001). In statin nonusers, C allele homozygotes at rs10770791 had a large absolute reduction in HbA_1c (0.48 ± 0.12% [5.2 ± 1.26 mmol/mol]), equivalent to that associated with initiation of a dipeptidyl peptidase 4 inhibitor.CONCLUSIONSWe have identified clinically important genetic effects at genome-wide levels of significance, and important drug-drug-gene interactions, which include commonly prescribed statins. With increasing availability of genetic data embedded in clinical records these findings will be important in prescribing glucose-lowering drugs.     

Effect Ketamine Infusion Protocol on Pain Management and Opioid Consumption in Opioid Tolerant Cancer Patients

“Oncology Massage (OM) is the adaptation of massage techniques to safely nurture the body of someone affected by cancer or its treatments.” Society for Oncology Massage(S40M) Oncology Massage (OM) is recognized &; practiced worldwide. Most noted benefits: reduced pain &; anxiety. OM, Esthetician provided Skin Care (ESC) clinically show positive impact on side effects, QOL during cancer therapy, recovery, survivorship. Ability to customize, innovate, services are tailored to individual needs, making OM/ESC suited for Pain Management (PM) integration. Adaptations accomodate for short, long term, late treatment effects, medical devices, medications, radiation, surgery, low blood counts, blood clots, fatigue, bone pain, lymphedema, lymphedema risk from lymph node biopsy/surgery/radiation. Venues: Spa day retreats, infusion centers, hospital-based, in-home, in-office. Clinical research: massage increases natural killer cells, lymphocytes; reduces nausea, pain, fatigue; improves/promotes sleep, body image, greater sense of well-being; eases feelings of isolation. Practitioners remain current with medical advancements. OM trained therapists safely assess, deliver treatment within a clinical framework for those in/with cancer treatment history. Estheticians regularly provide massage applications as part of skin care, plus treating skin conditions. Therapists preserve, promote skins acid mantle through product choices, adjusting bodywork, pressure, stroke direction, to not burden an interrupted/damaged/compromised lymphatic system. Skin treatments soothe, replenish those in treatment; strengthen, restore for those well into recovery. Aromatherapy, acupressure can be incorporated. OM utilizes gentle touch: stationary weightless hand applications; light lotioning; gentle massage. Too vigorous/demanding massage can cause pain, trigger inflammation, damage tissue, cause/aggravate lymphedema or development of systemic side effects such as flu-like symptoms. Best practices: MD release; intake evaluation; informed consent; client contact follow-up, care team feedback. Informed, prepared, communicative therapists understand role, presence importance, provide space to share. OM can safely contribute to care/QOL of PM clients/patients of all ages.     

Opioid Therapy for Chronic Pain: Risk Management Strategies

The use of opioids for chronic pain poses multiple challenges for nurse practitioners. While most clients with chronic pain can safely use these medications, there is a subset of patients who may exhibit aberrant behaviors during opioid therapy. These behaviors can indicate the possibility of drug diversion, substance abuse, or undertreated pain. Screening tools, opioid contracts, and urine drug testing may decrease clinician barriers to using opioids for chronic pain in primary care settings. The identification of at-risk patients before initiating opioids can optimize analgesia while safeguarding the legitimate use of these drugs to treat pain.     

The Relationship of Opioid Treatment in Chronic Pain Conditions: Implications on Brain Reward Response

An area of scientific understanding that remains unexplained is the effect of chronic pain conditions on the brain reward response to opioids. Substance misuse remains one of the most baffling areas of scientific evaluation, identification, and intervention given that very little is known about the mechanisms differentiating inevitable physiologic responses to opioids and dysfunctional or abnormal responses to long-term opioid administration. The effects of opioids on the brain reward system in persons with chronic pain is of significance to clinicians. Given the paucity of information available on opioid therapeutic use versus misuse in this population, however, the clinician is left to develop subjective conclusions about differentiation. Inevitable opiate effects include the linked concepts of tolerance to opioids, development of withdrawal phenomena, hyperalgesia, and pharmacologic resistance to the antinociceptive properties of opioids. This article evaluates current knowledge regarding relationships of these neuroadaptive responses to chronic opioid treatment coupled with chronic pain conditions and the combined effect of these factors on the brain reward system.     

Methadone as a First-Line Opioid in Cancer Pain Management: A Systematic Review

Aim

The objective of this review was to assess the existent evidence for the use of methadone as a first-line therapy in cancer pain management.

Gabapentin as an Adjuvant to Opioid Analgesia for Neuropathic Cancer Pain

Gabapentin was administered as an “add on” therapy to 22 patients with neuropathic cancer pain only partially responsive to opioid therapy. Global pain, burning pain, shooting pain episodes, and allodynia were assessed separately. Gabapentin was given for at least a week and efficacy was assessed after 7 to 14 days of therapy. Global pain score decreased from a mean (± SD) of 6.4 (± 1.5) to 3.2 (± 1.3) (95% confidence interval of the baseline minus final score differences [95% CI] = 1.0–2.4). Burning pain intensity decreased from a mean (± SD) of 5.1 (± 3.6) to 2.0 (± 2.3) (95% CI = 1.5–3.8), and episodes of shooting pain decreased in frequency from 7.2 (± 3.7) to 2.2 (± 2.2) daily episodes (95% CI = 1.8–4.3). Allodynia was found in 9 patients and disappeared in 7 during gabapentin administration. Twenty patients judged the new drug efficacious in relieving their symptoms. The potential role of gabapentin as an adjuvant to opioid analgesia in cancer pain is discussed.     

Chronic Opioid Pain Management for Chronic Kidney Disease

Questions from patients about pain conditions, pain treatment, and responses from authors are presented to help educate patients and make them effective self-advocates. The topics addressed in this issue are renal or kidney failure and chronic pain management with opioids, morphine, and oxycodone effect in the body over a period of time. This includes process of absorption, distribution, localization in tissues, biotransformation and excretion in chronic kidney disease, expected side effects and recommendations.     

Challenges Associated With Spinal Opioid Therapy for Pain in Patients With Advanced Cancer: A Report of Three Cases

Intraspinal opioid therapy has been increasingly used for the management of cancer pain refractory to traditional treatment. However, this approach may present challenges in patients with advanced cancer. Three cases are presented that highlight the challenges associated with using neuraxial analgesia to manage cancer pain that was felt to be “refractory” to conventional treatment. Before an invasive procedure, such as placement of a permanent intrathecal opioid delivery system, a rigorous assessment and treatment of total pain (physical, psychological, spiritual, social, and practical) by an interdisciplinary team would be prudent.     

Chronic Opioid Therapy in Cancer Survivors at a Specialty Oncology Pain Clinic: Opioid Dosing,Efficacy, and Safety During Five Years of Pain Management

There are limited data regarding long-term safety and efficacy in cancer survivors receiving chronic opioid therapy. With conflicting recommendations on opioid-prescribing practices and lack of available outcome data, this study aimed to provide a longitudinal perspective on opioid prescribing in cancer survivors. A retrospective chart review at a comprehensive cancer care center pain clinic used data from pain clinic provider notes from 2013 to 2018. Inclusion criteria were patients in clinical remission not receiving active chemotherapy or immunotherapy and receiving opioids during the study period. Opioid dosing changes and outcomes between zero and five years were evaluated by standard statistical analysis. Thirty-two patients met inclusion criteria. Solid malignancies were more common than hematologic malignancies (72% vs. 28%). Common pain complaints were related to postsurgical changes (43%), postradiation (32%), and chemotherapy-induced pain syndromes (25%). There were no serious adverse events. One patient exhibited possible aberrant behavior. At the initial visit, the median morphine milligram equivalent per day (MME/day) was 130. Median MME/day at Year 0 (study start) and Year 5 was 135 and 159, respectively (P = 0.475). Functional status was satisfactory in 58% at Year 0 and increased to 91% of patients meeting their functional goals at Year 5. In a carefully monitored group of cancer survivors with persistent pain, chronic opioid therapy was safely managed during extended periods without significant opioid escalation or evidence of serious adverse events including aberrant behaviors. This population benefited when opioid therapy was managed with a focus on function rather than reduction of pain intensity scores.     

Managing Cancer Pain in Patients with Opioid and Substance Use Disorders

ObjectiveTo discuss the assessment and management of pain in patients with substance use disorders.Data SourcesPeer-reviewed articles, book chapters, internet sources.ConclusionPatients should be routinely assessed for SUDs. Pain management should be stratified according to patient risk. An interdisciplinary approach is essential.Implications for Nursing PracticeOncology nurses should be aware of assessment approaches to screen and monitor patients with SUDs. Oncology nurses are an essential part of the interdisciplinary team when monitoring patients with SUDs.     

Topical Analgesics in the Management of Acute and Chronic Pain

Oral analgesics are commonly prescribed for the treatment of acute and chronic pain, but these agents often produce adverse systemic effects, which sometimes are severe. Topical analgesics offer the potential to provide the same analgesic relief provided by oral analgesics but with minimal adverse systemic effects. This article describes the results of a systematic review of the efficacy of topical analgesics in the management of acute and chronic pain conditions. A literature search of MEDLINE/PubMed was conducted using the keywords topical analgesic AND chronic pain OR acute pain OR neuropathic pain and focused only on individual clinical trials published in English-language journals. The search identified 92 articles, of which 65 were eligible for inclusion in the review. The most commonly studied topical analgesics were nonsteroidal anti-inflammatory drugs (n=27), followed by lidocaine (n=9), capsaicin (n=6), amitriptyline (n=5), glyceryl trinitrate (n=3), opioids (n=2), menthol (n=2), pimecrolimus (n=2), and phenytoin (n=2). The most common indications were acute soft tissue injuries (n=18), followed by neuropathic pain (n=17), experimental pain (n=6), osteoarthritis and other chronic joint-related conditions (n=5), skin or leg ulcers (n=5), and chronic knee pain (n=2). Strong evidence was identified for the use of topical diclofenac and topical ibuprofen in the treatment of acute soft tissue injuries or chronic joint-related conditions, such as osteoarthritis. Evidence also supports the use of topical lidocaine in the treatment of postherpetic neuralgia and diabetic neuropathy. Currently, limited evidence is available to support the use of other topical analgesics in acute and chronic pain.     

Implications of Bariatric Surgery on Chronic Pain and Opioid Use

Questions from patients about pain conditions, pain treatment, and responses from authors are presented to help educate patients and make them effective self-advocates. The topics addressed in this report are implications of bariatric surgery or weight loss surgery on chronic pain and opioid use, what to expect with regards to pain control, and the need to change opioid dose after bariatric surgery.     

Barriers to Pain Management among Adolescents with Cancer

Patient-related barriers to reporting pain and using analgesics (e.g., fear of addiction) can detrimentally affect pain management for adolescents with cancer. However, adolescent barriers have not been systematically investigated; furthermore, no instrument exists to measure these barriers. The purposes of this study were to examine the psychometric properties of the newly developed Adolescent Barriers Questionnaire (ABQ) and to describe adolescent barriers to pain management. The study was guided by a barriers model which suggests that barriers (beliefs) influence coping (hesitation to report pain, use of analgesics, and adequacy of analgesics), which in turn affects outcomes (pain severity and quality of life). Sixty adolescent patients with cancer aged 12-17 years completed the ABQ; 22 of which reported pain and also completed measures of hesitation, analgesic use, pain severity, and physical and psychosocial function. Initial testing provided evidence that the ABQ is reliable and valid. Internal consistency estimates for the total scale ranged from 0.91 to 0.94 and for the subscales ranged from 0.54 to 0.96. Test-retest reliability over a 2-week period was r = 0.82. Construct validity was supported by a significant positive relationship between barriers scores and coping (hesitation to report pain and to use analgesics). However, coping did not mediate the relationship between barriers and outcomes. All of the adolescents reported some barriers. Barriers scores did not vary by age or gender. The leading barrier was concern that social activities would be restricted if pain was reported. Clearly, adolescents have barriers that can interfere with pain management. Interventions are needed to identify and help adolescents overcome these barriers.