Mirogabalin: a novel gabapentinoid or another false dawn?

PURPOSE OF REVIEW: Mirogabalin is a novel gabapentinoid medication for the treatment of neuropathic pain. The purpose of this review is to discuss current evidence for its use. Gabapentinoids are widely prescribed for neuropathic pain. Mirogabalin offers theoretical advantages over traditional gabapentinoids due to its specificity for the α2δ-1 subunit of voltage-gated calcium channels. It is theorised that this specificity may reduce adverse drug reactions by minimising binding to the α2δ-2 subunit which is responsible for many of the gabapentinoid side effects. RECENT FINDINGS: Mirogabalin's slower dissociation from the α2δ-1 compared with α2δ-2, and its higher potency may also impart an efficacy benefit over traditional gabapentinoids. These theoretical advantages of mirogabalin remain inconclusive in clinical practice, with mixed evidence regarding mirogabalin versus traditional gabapentinoids. Some studies suggest a reduced side effect profile yet, others fail to demonstrate significant differences. Regarding efficacy, mirogabalin may be superior to placebo for several neuropathic pain syndromes, but evidence of widespread benefit over traditional gabapentinoids is currently lacking. SUMMARY: Mirogabalin offers theoretical promise, but large, independent studies are required to further assess its performance versus traditional gabapentinoids.

Opioid use disorder in cancer patients.

PURPOSE OF REVIEW: The misuse of opioids has increased significantly in recent decades. Historically, cancer patients have not been considered at risk of opioid misuse. However, cancer pain is common, and opioids are often prescribed. Guidelines addressing opioid misuse often exclude cancer patients. Given that misuse is associated with significant harm and a reduction in quality of life, it is important to understand the risk of opioid misuse in cancer patients and how we can recognise and treat it. RECENT FINDINGS: Early cancer diagnoses and treatments have improved cancer survival rates, leading to a larger population of cancer patients and survivors. Opioid use disorder (OUD) may precede a cancer diagnosis or may develop during or after treatment. The effect of OUD extends from an individual patient to a societal level. This review examines the increasing incidence of OUD in cancer patients, ways to identify patients with OUD such as behaviour change and screening scales, prevention of OUD such as limited and targeted opioid prescriptions, and evidence-based treatment suggestions for OUD. SUMMARY: OUD in cancer patients has only relatively recently been recognised as a growing problem. Early identification, involvement of the multidisciplinary team, and treatment can reduce the negative impact of OUD.

Pain in the Cancer Survivor.

Recent decades have demonstrated significant strides in cancer screening, diagnostics and therapeutics. As such there have been dramatic changes in survival following a diagnosis of cancer.

Clinical practice guidelines for cancer pain: problems and solutions.

PURPOSE OF REVIEW: Clinical practice guidelines (CPGs) should allow practitioners to follow the best evidence-based management for patients. The increasing specialisation of medicine and pain medicine has increased the number of CPGs, but practitioners are still facing contradictory advice that can be difficult to implement and follow. RECENT FINDINGS: A recent comprehensive metareview of 25 reviews have highlighted that the same issues of quality, barriers to implementation and difficulties in applicability are as prevalent as they were years ago when assessment tools (e.g. AGREE II) and recommendations for CPG development were introduced. There remains a lack of consistency of recommendations and quality of evidence for CPGs in cancer pain that impedes the ability to provide the 'best' management for patients. SUMMARY: Even the most renowned and apparently high-quality CPGs in many specialities, including cancer pain, still are potentially deficient especially in terms of applicability, implementation, and transparency of conflicts of interest. Despite the increased scrutiny, in part related to the opioid crisis, the situation has not changed. The development of CPGs should engender collaboration with multiple stakeholder groups and focus on transparency and facilitating implementation.

Perioperative Pain and Addiction Interdisciplinary Network (PAIN): consensus recommendations for perioperative management of cannabis and cannabinoid-based medicine users by a modified Delphi process.

In many countries, liberalisation of the legislation regulating the use of cannabis has outpaced rigorous scientific studies, and a growing number of patients presenting for surgery consume cannabis regularly. Research to date suggests that cannabis can impact perioperative outcomes. We present recommendations obtained using a modified Delphi method for the perioperative care of cannabis-using patients. A steering committee was formed and a review of medical literature with respect to perioperative cannabis use was conducted. This was followed by the recruitment of a panel of 17 experts on the care of cannabis-consuming patients. Panellists were blinded to each other's participation and were provided with rater forms exploring the appropriateness of specific perioperative care elements. The completed rater forms were analysed for consensus. The expert panel was then unblinded and met to discuss the rater form analyses. Draft recommendations were then created and returned to the expert panel for further comment. The draft recommendations were also sent to four independent reviewers (a surgeon, a nurse practitioner, and two patients). The collected feedback was used to finalise the recommendations. The major recommendations obtained included emphasising the importance of eliciting a history of cannabis use, quantifying it, and ensuring contact with a cannabis authoriser (if one exists). Recommendations also included the consideration of perioperative cannabis weaning, additional postoperative nausea and vomiting prophylaxis, and additional attention to monitoring and maintaining anaesthetic depth. Postoperative recommendations included anticipating increased postoperative analgesic requirements and maintaining vigilance for cannabis withdrawal syndrome.

Recent advances in understanding chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common cause of pain and poor quality of life for those undergoing treatment for cancer and those surviving cancer. Many advances have been made in the pre-clinical science; despite this, these findings have not been translated into novel preventative measures and treatments for CIPN. This review aims to give an update on the pre-clinical science, preventative measures, assessment and treatment of CIPN.

Comparison of Imaging Changes and Pain Responses in Patients with Intra- or Extraosseous Bone Metastases Treated Palliatively with Magnetic Resonance-Guided High-Intensity-Focused Ultrasound.

PURPOSE: This study compared changes in imaging and in pain relief between patients with intraosseous, as opposed to extraosseous bone metastases. Both groups were treated palliatively with magnetic resonance-guided high-intensity-focused ultrasound (MRgHIFU). MATERIALS AND METHODS: A total of 21 patients were treated prospectively with MRgHIFU at 3 centers. Intraprocedural thermal changes measured using proton resonance frequency shift (PRFS) thermometry and gadolinium-enhanced T1-weighted (Gd-T1W) image appearances after treatment were compared for intra- and extraosseous metastases. Pain scores and use of analgesic therapy documented before and up to 90 days after treatment were used to classify responses and were compared between the intra- and extraosseous groups. Gd-T1W changes were compared between responders and nonresponders in each group. RESULTS: Thermal dose volumes were significantly larger in the extraosseous group (P = 0.039). Tumor diameter did not change after treatment in either group. At day 30, Gd-T1W images showed focal nonenhancement in 7 of 9 patients with intraosseous tumors; in patients with extraosseous tumors, changes were heterogeneous. Cohort reductions in worst-pain scores were seen for both groups, but differences from baseline at days 14, 30, 60, and 90 were only significant for the intraosseous group (P = 0.027, P = 0.013, P = 0.012, and P = 0.027, respectively). By day 30, 67% of patients (6 of 9) with intraosseous tumors were classified as responders, and the rate was 33% (4 of 12) for patients with extraosseous tumors. In neither group was pain response indicated by nonenhancement on Gd-T1W. CONCLUSIONS: Intraosseous tumors showed focal nonenhancement by day 30, and patients had better pain response to MRgHIFU than those with extraosseous tumors. In this small cohort, post-treatment imaging was not informative of treatment efficacy.

Cancer pain: where are we now?

Increasing numbers of those living with and beyond cancer presents a clinical challenge for pain specialists. A large proportion of these patients experience pain secondary to their disease or its treatment, impeding rehabilitation and significantly impacting upon their quality of life. The successful management of this pain presents a considerable challenge. This review aims to outline current concepts and treatment options, while considering nuances within pain assessment and the use of large-scale data to help guide further advances.

Post-herpetic neuralgia - a review of current management and future directions.

INTRODUCTION: Post-herpetic neuralgia (PHN) is common and treatment is often suboptimal with less than half of patients achieving adequate 50% pain relief. As an area of unmet clinical need and as an archetype of neuropathic pain, it deserves the attention of clinicians and researchers. Areas covered: This review summarises the epidemiology, pathophysiology, risk factors and clinical features of varicella infection. It describes the current and possible future management strategies for preventing varicella infection and reactivation and for treating PHN. Expert opinion: A highly successful Varicella Zoster (VZV) vaccine has not been universally adopted due to fears that it may increase Herpes Zoster (HZ) incidence - and thus PHN - in older, unvaccinated generations. This is a controversial theory but advances in the efficacy of vaccines against HZ may allay these fears and encourage more widespread adoption of the VZV vaccine. Treatment of PHN, as for any neuropathic pain, must be multidisciplinary and multimodal. Advances in sensory phenotyping technology and genomics may allow more individualised treatment. Traditional research methodologies are ill-suited to assess the kind of complex interventions that are necessary to achieve better clinical outcomes in this challenging field.

Is tapentadol different from classical opioids? A review of the evidence.

Tapentadol is a single molecule able to deliver analgesia by two distinct mechanisms, a feature which differentiates it from many other analgesics. Pre-clinical data demonstrate two mechanisms of action: mu-opioid receptor agonist activity and noradrenaline re-uptake inhibition. From these, one may predict that tapentadol would be applicable across a broad spectrum of pain from nociceptive to neuropathic. The evidence in animal models suggests that norepinephrine re-uptake inhibition (NRI) is a key mechanism and may even predominate over opioid actions in chronic (and especially neuropathic) pain states, reinforcing that tapentadol is different to classical opioids and may, therefore, be an a priori choice for the treatment of neuropathic and mixed pain. The clinical studies and subsequent practice experience and surveillance support the concept of opioid and non-opioid mechanisms of action. The reduced incidence of some of the typical opioid-induced side effects, compared to equianalgesic doses of classical opioids, supports the hypothesis that tapentadol analgesia is only partially mediated by opioid agonist mechanisms. Both the pre-clinical and clinical profiles appear to be differentiated from those of classical opioids.

Opioids and cancer: friend or foe?

PURPOSE OF REVIEW: Most cancer patients experience pain and many will require opioids. However, the effects of opioids on cancer progression, metastasis, and recurrence is increasingly being questioned. There is evidence that opioids affect immune system function, angiogenesis, apoptosis, and invasion in a potentially deleterious manner. This review will examine the preclinical and clinical evidence. RECENT FINDINGS: Recent clinical data have struggled to find robust evidence that opioids promote cancer progression. Although most study has involved morphine, differential effects of other opioids on immune function and cancer are revealing a more complex picture. SUMMARY: Although there is a biologically plausible story, evidence for the action of opioids on cancer is mixed. Indeed, it may even be that in the chronic setting morphine has a beneficial effect on outcome in certain cancer types. This review critically examines and evaluates the evidence for the action of opioids on the processes involved in cancer progression. In the light of the uncertainty of opioid effect on cancer, any decision making should be tempered by knowing that stress and pain undoubtedly contribute to cancer progression.

Quality of transition to end-of-life care for cancer patients in the intensive care unit.

BACKGROUND: There have been few studies that have evaluated the quality of end-of-life care (EOLC) for cancer patients in the ICU. The aim of this study was to explore the quality of transition to EOLC for cancer patients in ICU. METHODS: The study was undertaken on medical patients admitted to a specialist cancer hospital ICU over 6 months. Quantitative and qualitative methods were used to explore quality of transition to EOLC using documentary evidence. Clinical parameters on ICU admission were reviewed to determine if they could be used to identify patients who were likely to transition to EOLC during their ICU stay. RESULTS: Of 85 patients, 44.7% transitioned to EOLC during their ICU stay. Qualitative and quantitative analysis of the patients' records demonstrated that there was collaborative decision-making between teams, patients and families during transition to EOLC. However, 51.4 and 40.5% of patients were too unwell to discuss transition to EOLC and DNACPR respectively. In the EOLC cohort, 76.3% died in ICU, but preferred place of death known in only 10%. Age, APACHE II score, and organ support, but not cancer diagnosis, were identified as associated with transition to EOLC (p = 0.017, p < 0.0001 and p = 0.001). CONCLUSIONS: Advanced EOLC planning in patients with progressive disease prior to acute deterioration is warranted to enable patients' wishes to be fulfilled and ceiling of treatments agreed. Better documentation and development of validated tools to measure the quality EOLC transition on the ICU are needed.

Pain in cancer survivors.

Cancer and its treatment exert a heavy psychological and physical toll. Of the myriad symptoms which result, pain is common, encountered in between 30% and 60% of cancer survivors. Pain in cancer survivors is a major and growing problem, impeding the recovery and rehabilitation of patients who have beaten cancer and negatively impacting on cancer patients' quality of life, work prospects and mental health. Persistent pain in cancer survivors remains challenging to treat successfully. Pain can arise both due to the underlying disease and the various treatments the patient has been subjected to. Chemotherapy causes painful chemotherapy-induced peripheral neuropathy (CIPN), radiotherapy can produce late effect radiation toxicity and surgery may lead to the development of persistent post-surgical pain syndromes. This review explores a selection of the common causes of persistent pain in cancer survivors, detailing our current understanding of the pathophysiology and outlining both the clinical manifestations of individual pain states and the treatment options available.