Cancer-related Neuropathic Pain Research Articles

Cancer-Related Neuropathic Pain, Chemotherapy-Induced Peripheral Neuropathy and Cognitive Decline in a 5-Year Prospective Study of Patients with Breast Cancer-NEON-BC.

This study aims to estimate the prevalence and to identify the determinants of cancer-related neuropathic pain (CRNP), chemotherapy-induced peripheral neuropathy (CIPN) and cognitive decline among patients with breast cancer over five years after diagnosis. Women with an incident breast cancer (n = 462) and proposed for surgery were recruited at the Portuguese Institute of Oncology-Porto in 2012 and underwent systematic neurological examinations and evaluations with the Montreal Cognitive Assessment (MoCA) before treatment and after one, three, and five years. Multivariate logistic regression was used to assess the determinants of CRNP and CIPN, and multivariate linear regression for the variation in MoCA scores. Prevalence of CRNP and CIPN decreased from the first to the fifth year after diagnosis (CRNP: from 21.1% to 16.2%, p = 0.018; CIPN: from 22.0% to 16.0% among those undergoing chemotherapy, p = 0.007). Cognitive impairment was observed in at least one assessment in 17.7% of the women. Statistically significant associations were observed between: cancer stage III and both CRNP and CIPN; triple negative breast cancer, chemotherapy, axillary node dissection, older age, higher education, and being single and CRNP; taxanes and fruit and vegetable consumption and CIPN. Anxiety, depression and poor sleep quality at baseline were associated with decreases in MoCA values from pre- to post-treatment and with CRNP. Follow-up protocols should consider the persistence of CRNP, CIPN, and cognitive impairment for several years following diagnosis.

Contribution of immune cells to cancer-related neuropathic pain: An updated review.

Given that the incidence of cancer is dramatically increasing nowadays, cancer-related neuropathic pain including tumor-related and therapy-related pain gradually attracts more attention from researchers, which basically behaves as a metabolic-neuro-immune disorder with worse clinical outcomes and prognosis. Among various mechanisms of neuropathic pain, the common underlying one is the activation of inflammatory responses around the injured or affected nerve(s). Innate and adaptive immune reactions following nerve injury together contribute to the regulation of pain. On the other hand, the tumor immune microenvironment involving immune cells, as exemplified by lymphocytes, macrophages, neutrophils and dendritic cells, inflammatory mediators as well as tumor metastasis have added additional characteristics for studying the initiation and maintenance of cancer-related neuropathic pain. Of interest, these immune cells in tumor microenvironment exert potent functions in promoting neuropathic pain through different signaling pathways. To this end, this review mainly focuses on the contribution of different types of immune cells to cancer-related neuropathic pain, aims to provide a comprehensive summary of how these immune cells derived from the certain tumor microenvironment participate in the pathogenesis of neuropathic pain. Furthermore, the clarification of roles of various immune cells in different tumor immune microenvironments associated with certain cancers under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction, and thereby provides more opportunities for novel approaches for the prevention and treatment of cancer-related neuropathic pain.

ID: 197332 Radiotherapy for a Patient With a Spinal Cord Stimulator: A Case Report

Cancer-related neuropathic pain has a prevalence of up to 40% in advanced disease. Spinal cord stimulators (SCS) are used in chronic pain when other treatment modalities are not sufficient to relieve pain. Radiotherapy is a common cancer treatment modality that can damage electrical devices, including SCS. We present the case of a patient with an SCS that required radiotherapy, after a multidisciplinary approach the radiotherapy was completed without the need for SCS removal.

Oral Methadone versus Morphine IR for Patients with Cervical Cancer and Neuropathic Pain: A Prospective Randomised Controlled Trial.

In India, cervical cancer is the most common cancer among women and makes up for up to 29% of all registered cancer in females. Cancer-related pain is one of the major distressing symptoms for all cancer patients. Pain is characterised as somatic or neuropathic, and the total pain experience is often mixed. Conventional opioids are the backbone of analgesic treatment but are most often not sufficient in alleviating neuropathic pain, common in cervical cancer. Accumulating evidence of the advantage of methadone compared to conventional opioids, due to agonist action at both μ and q opioid receptors, N-methyl-D-aspartate (NMDA) antagonist activity and the ability to inhibit the reuptake of monoamines has been demonstrated. We hypothesised that, with these properties', methadone might be a good option for the treatment of neuropathic pain in patients with cervical cancer. Patients with cervical cancer stages ll-lll were enrolled in this randomized controlled trial. A comparison was made between methadone versus immediate release morphine (IR morphine), with increasing doses until pain was controlled. Inclusion-period was from October 3rd to December 31st 2020, and the total patient-study period was 12 weeks. Pain intensity was assessed according to the Numeric Rating Scale (NRS) and Douleur Neuropathique (DN4). The primary objective was to determine whether methadone was clinically superior versus noninferior to morphine as an analgesic for the treatment of cancer related neuropathic pain in women with cervical cancer. A total of 85 women were included; five withdrew and six died during the study period, leaving 74 patients completing the study. All participants showed a reduction in mean values of NRS and DN4 from the time of inclusion and to the end of the study period, for IR morphine and methadone 8.4-2.7 and 8.6-1.5, respectively (P < 0.001). The DN4 score mean reduction for Morphine and Methadone were 6.12-1.37 and 6.05-0, respectively (P < 0.001). Side effects were more common in the group of patients receiving IR morphine compared to the patients treated with methadone. We found that Methadone had a superior analgesic effect with good overall tolerability compared with morphine as a first-line strong opioid for the management of cancer-related neuropathic pain.

Multidisciplinary Approaches: Cingulotomy in an Adult With Refractory Neuropathic Cancer-Related Pain.

Background: Oral medications, intravenous medications, and invasive interventions are effective means of neuropathic pain control. In patients with pain refractory to more conventional approaches, cingulum bundle ablation is an alternative treatment modality not routinely considered by providers. Case Description: A 42-year-old woman with history of cervical cancer in remission presented with intractable left lower extremity pain. Workup revealed radiation-induced left iliopsoas osteosarcoma complicated by deep venous occlusion and thrombosis. Her pain remained intractable to pharmacologic therapies and more invasive pain control interventions. A multidisciplinary decision was made to pursue bilateral subcortical cingulum bundle radiofrequency ablation. After a technically successful surgery, the patient exhibited improved pain control as evidenced by a decline in her numerical rating scale of pain and analgesic medication requirements. Conclusion: Cancer-related neuropathic pain often requires treatment with multiple modalities involving multidisciplinary teams. In select refractory cases, cingulum bundle ablation may be an effective alternative treatment modality.

Lidocaine transdermal patches reduced pain intensity in neuropathic cancer patients already receiving opioid treatment

BackgroundLimited efficacy has been observed when using opioids to treat neuropathic pain. Lidocaine patches reduce neuropathic pain in postherpetic neuralgia, but their benefits for cancer-related neuropathic pain remain unclear. This study aimed to investigate a treatment for cancer-related neuropathic pain.MethodsWe conducted a prospective, open-label, single-arm study to assess the efficacy and safety of lidocaine transdermal patches in patients experiencing localized, superficial, neuropathic cancer pain. Terminal cancer patients already receiving opioid treatment participated in the 3-day study. The primary endpoint was pain intensity evaluated by the numerical rating scale (NRS). The secondary endpoints were the pain relief score and the quality of analgesic treatment.ResultsThe results showed a significant difference in the median NRS over 3 days (Kruskal–Wallis test, p < 0.0001). The median NRS pain intensity from Day 1 to Day 3 was 4.0 with 95% C.I. (3.3, 5.0), 3.0 (2.5, 3.5), and 2.6 (2.0, 3.0), respectively. The difference between the median NRS pain intensities of any 2 days was significant (Wilcoxon signed-rank test, p < 0.0001). The generalized estimating equation (GEE) estimation model showed significant differences between the NRS pain intensities on any 2 days. There was no significant difference in the pain relief score or the quality of analgesic treatment.ConclusionsIn this study, the 5% lidocaine transdermal patch reduced the NRS pain intensity in neuropathic cancer patients already receiving opioid treatment. Treatment of localized and superficial neuropathic pain caused by cancer was well tolerated and effective.

Sigma Antagonists for Treatment of Neuropathic Pain Syndromes in Cancer Patients: A Narrative Review

Almost 40% of cancer patients have neuropathic pain or mixed pain with a neuropathic component, which can be intense, debilitating, and challenging to treat. New studies on sigma receptors show these enigmatic ligand-binding protein chaperones may be helpful drug targets for new pharmacologic options to reduce many types of neuropathies, including chemotherapy-induced peripheral neuropathy (CIPN) and other cancer-related neuropathic pain syndromes. Our objective was to review the literature, including preclinical findings, in support of sigma-1 receptor (S1R) antagonists in reducing neuropathic pain and sigma-2 receptor (S2R) agonists for neuroprotection. The mechanisms behind these effects are not yet fully elucidated. The role of S1R antagonists in treating CIPN appears promising. In some cases, combination therapy of an opioid—which is a true analgesic—with a S1R antagonist, which is an anti-hyperalgesic and anti-allodynic agent, has been proposed. Of interest, but not well studied is whether or not S1R antagonists might be effective in treating CIPN in patients with pre-existing peripheral diabetic neuropathy. While neuropathic syndromes may occur with hematologic cancers, the role of S1R agonists may be effective. Sigma receptors are being actively studied now for a variety of conditions ranging from Alzheimer’s disease to Parkinson’s disease as well as neuropathic pain.

Diagnosis, management and impact on patients' lives of cancer-related neuropathic pain (CRNP): A European survey.

This study assessed the impact of cancer-related neuropathic pain (CRNP) on patients and the importance of the patient-healthcare professional (HCP) relationship in diagnosis and management. A quantitative online survey was conducted involving adult patients from 13 European countries who had been diagnosed with treatable cancer and experienced symptoms of peripheral neuropathy. Of 24,733 screened respondents, 549 eligible persons met the inclusion criteria and completed the questionnaire. Among individuals still experiencing pain, 75% rated it as 'severe' or 'moderate'. In addition, 61% reported a negative impact on day-to-day activities, and 30% said they had stopped working as a result. A third of respondents had received no diagnosis of CRNP despite reporting painful symptoms to an HCP. HCPs spending enough time discussing pain and understanding the impact on patients' lives were each associated with an increased likelihood of a formal CRNP diagnosis. Compared with individuals currently in active cancer treatment, cancer survivors were less likely to have a diagnosis of CRNP or regular pain conversations with HCPs. CRNP remains under-recognised despite its substantial impact on patients' lives. Clinical practice may be improved by strengthening patient-HCP relationships around pain discussions and increasing the focus on pain management among cancer survivors.

Worldwide Productivity and Research Trend of Publications Concerning Cancer-Related Neuropathic Pain: A Bibliometric Study.

Cancer-related neuropathic pain is a common adverse effect in the process of cancer development and treatment and has gradually attracted the attention of researchers. The purpose of this article is to systematically review the articles on cancer-related neuropathic pain published between 2012 and 2021 and visualize the data through CiteSpace and R software. The results show that in the past 10 years, a total of 5715 articles have been published, involving 118 categories, of which the most is Clinical Neurology, followed by Neurosciences, Pharmacology Pharmacy. The country with the most published articles is the United States, followed by China and Italy. A total of 22,228 authors were involved in the study of cancer-related neuropathic pain. These historical opinions about cancer-related neuropathic pain could be an important practical basis for further research into potential development trends.

1571P Cancer-related neuropathic pain (CRNP) in Europe: Impact of cancer stage on diagnosis and treatment of patients

Cancer-related neuropathic pain (CRNP) is common but is difficult to diagnose and treat in clinical practice (Edwards et al., 2019). A European patient survey was conducted to assess the impact of CRNP on patients and whether there are any differences in pain support across the cancer journey.

A Delphi Study on the Management of Neuropathic Cancer Pain in Spain: The DOLNEO Study.

PurposeThe objectives of this project were to assess the current situation and management of cancer-related neuropathic pain (CRNP) in Spain and to provide specific recommendations for the assessment, diagnosis and treatment of CRNP using a Delphi methodology.MethodsThis was a qualitative study that followed a Delphi methodology using a questionnaire with 56 statements that were grouped into 5 areas related to CRNP: prevalence and impact, pathophysiology, assessment and diagnosis, specific syndromes, treatment, and multidisciplinary approach. Based on the responses, the scientific committee prepared an algorithm and a recommended pathway for the management of CRNP.ResultsSeventy-nine physicians attended the meeting and completed the questionnaire. Consensus was reached for all statements relating to the prevalence and impact of CRNP. However, the perceptions of specialists from palliative care of the frequency and impact of CRNP differed from those of other specialists. A high degree of consensus was reached for all statements concerning the assessment and diagnosis of CRNP. Regarding specific syndromes, the only statement with a lack of consensus was that on the frequency of NP in patients undergoing radiotherapy. There were some disagreements regarding the multidisciplinary approach and referral criteria for the management of NP.ConclusionOur results show a large degree of agreement on the assessment, diagnosis and treatment of cancer-related neuropathic pain among the specialists involved in its management. There were, however, some disagreements regarding the multidisciplinary approach and referral criteria for the management of neuropathic pain.

New analgesics in cancer pain

Cancer pain continues to be a significant problem despite the range of analgesic and adjuvant medications available. The purpose of this review is to explore the most recent developments in the management of cancer pain. Tapentadol, launched in the United Kingdom in May 2011, represents the last new analgesic entity with a novel mode of action to enter clinical practice for moderate-to-severe pain. Recent evidence describes the benefit of duloxetine for cancer-related neuropathic pain, and parecoxib by continuous subcutaneous infusion for refractory cancer pain. There is interest in the role of cannabinoids in cancer pain management but much of the evidence to date is in chronic noncancer pain. Conflicting evidence complicates the role that biased opioid agonism may offer in terms of alternative analgesics in the future. There is development of new drugs with clinical utility on the horizon but a need for high-quality, randomized controlled trials specifically assessing efficacy and tolerability in cancer pain.

Prevalence and Persistence of Anxiety and Depression over Five Years since Breast Cancer Diagnosis-The NEON-BC Prospective Study.

Anxiety and depression are frequent among patients with breast cancer (BCa). Evidence of the persistence and recovery from these conditions and their determinants is scarce. We describe the occurrence of clinically significant anxiety and depression symptoms and their associated factors among BCa patients. A total of 506 women admitted in 2012 at the Portuguese Institute of Oncology of Porto were evaluated before treatment and after one, three, and five years (7.9% attrition rate). The five-year prevalence of anxiety and/or depression (Hospital Anxiety and Depression Scale, subscores ≥ 11) was 55.4%. The peak prevalence for anxiety was before treatment (38.0%), and after one year for depression (13.1%). One in five patients with anxiety/depression at baseline had persistent anxiety/depression over time, while only 11% and 22% recovered permanently from anxiety and depression, respectively, during the first year. Higher education, higher income, practicing physical activity, and adequate fruit and vegetable intake were protective factors against anxiety and/or depression. Loss of job and income, anxiolytics and antidepressants, cancer-related neuropathic pain, and mastectomy were associated with higher odds of anxiety and/or depression. These results highlight the importance of monitoring anxiety/depression during the first five years after cancer diagnosis and identify factors associated with these conditions.

Cancer-related neuropathic pain (CRNP) in Europe: What are the gaps in diagnosis and treatment from patients' perspective?

Cancer burden on individuals and society is high with 2.7 million new cancer cases per year in Europe. With effective treatments available, people with cancer live longer but often with sequelae such as neuropathic pain resulting from the cancer or its treatment. People with cancer experiencing neuropathic pain from 13 European countries shared their experiences with the diagnosis and management of their pain.

Intravenous lidocaine in cancer-related neuropathic pain: case series

Introduction: Administering systemic lidocaine has been shown to deliver effective analgesia for both cancer-related and non-cancer pain. Adverse effects and toxicity are rare with controlled administration.&#x0D; Objective: To report the results obtained after the indication to manage with IV lidocaine infusion to control neuropathic pain flares in 9 cancer patients.&#x0D; Methodology: Observational, descriptive, case series-type study. A search was conducted in the files of the Pain and Palliative Care Service of the National Cancer Institute - Instituto Nacional de Cancerología - in Bogotá. Patients over 18 years old diagnosed with cancer, who experienced high intensity neuropathic pain and with the cognitive ability to rate their pain in a numerical analogue scale (NAS), without any absolute contraindications for the use of IV lidocaine were included; patients were assessed between September 27 and November 21, 2019.&#x0D; Results: 9 patients experiencing a pain flare-up which was characterized as neuropathic were registered, of which 89 % had some improvement following the administration of an initial lidocaine bolus. After one hour, 60 % reported over 40% improvement in the initial NAS. After 24 hours all patients had experienced some improvement, with a reduction of 46% in the pain scale as compared to the baseline.&#x0D; Conclusions: In this series of cases, the intravenous infusion of lidocaine as an option for the management of neuropathic pain flares seems to reduce pain intensity following the initial bolus administration.

Preliminary effects of low-intensity focused ultrasound treatment program for cancer-related neuropathic pain.

Aim: To evaluate the effectiveness of low-intensity focused ultrasound (LIFU) therapy in the management of cancer-related neuropathic pain (CNP). Methods: A retrospective review with 22 patients with CNP treated with LIFU therapy (frequency 3Hz, 3W/cm2, pulse mode duty cycle 50%) was conducted. Results: Out of the 22 patients, 15 had CNP secondary to chemotherapy-induced peripheral neuropathy. Compared with baseline, there was a significant reduction in numeric pain rating scale(p<0.001). Additionally, 76.5% of patients (n=13) were considered to be responders to LIFU therapy. Conclusion: LIFU therapy may be a viable treatment modality in the management of CNP, specifically chemotherapy-induced peripheral neuropathy, with a minimal side effect profile. Larger, prospective studies with a structured protocol are necessary.

Ketamine Use for Cancer and Chronic Pain Management.

Ketamine, an N-methyl-D-aspartate receptor antagonist, is widely known as a dissociative anesthetic and phencyclidine derivative. Due to an undesirable adverse event profile when used as an anesthetic it had widely fallen out of human use in favor of more modern agents. However, it has recently been explored for several other indications such as treatment resistant depression and chronic pain. Several recent studies and case reports compiled here show that ketamine is an effective analgesic in chronic pain conditions including cancer-related neuropathic pain. Of special interest is ketamine’s opioid sparing ability by counteracting the central nervous system sensitization seen in opioid induced hyperalgesia. Furthermore, at the sub-anesthetic concentrations used for analgesia ketamine’s safety and adverse event profiles are much improved. In this article, we review both the basic science and clinical evidence regarding ketamine’s utility in chronic pain conditions as well as potential adverse events.

The Burden of Cancer-related Neuropathic Pain: A Multi-centric Cross-sectional Observational Study from North India.

Introduction:Neuropathic cancer pain is a common consequence of cancer itself and anti-cancer treatments. It is a complex phenomenon, often underdiagnosed by physicians or underreported by patients. Its diagnosis and management are usually more challenging than nociceptive pain. There is a dearth of epidemiological evidence for neuropathic pain in cancer patients in India. Screening questionnaires serve as a quick guide to identify potential cases of neuropathic pain. The aim of the present study was to identify the burden of cancer-related neuropathic pain using the Self-reported version of the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) pain scale.Methodology:This was a cross-sectional, observational, multi-centric study conducted at three hospitals in North India. From January 2017 to October 2017, patients attending pain clinic were screened for participation in the study. Adults aged ≥18 years and experiencing the pain of oncologic origin were eligible to participate in the study if they provided informed consent. S-LANSS questionnaire was used to screen patients with neuropathic pain.Results:From a total of 261 patients, who were enrolled in the study, 56.7% were male and their mean age was 50.87 (18–80) years. Fifty-four percent patients had pain with predominantly neuropathic component (S-LANSS score ≥10).Conclusion:High burden of neuropathic cancer pain has been observed in outpatient palliative care settings. Early diagnosis of neuropathic pain through screening questionnaires can serve as a quick guide for physicians in resource-constrained settings. This will allow identification of the neuropathic component of pain in patients suffering with mixed pain.

An evaluation of adult cancer-related neuropathic pain treatment at a large academic medical center.

168 Background: Cancer-related neuropathic pain (CNP) is a common comorbidity among patients due to treatment and/or tumors that can cause neuronal damage. At present, there is no proven method to prevent CNP and no published widely followed national guideline for CNP management with a defined treatment algorithm. Further evaluation of CNP treatment is needed to help guide the development of clinical algorithms for CNP management. Methods: Health Data Compass, a data mining warehouse, was used to identify adults treated at the University of Colorado Hospital (UCH) who had a new diagnosis of cancer between January 1, 2014 and May 31, 2019 in addition to neuropathy during the same time frame. Individual patient electronic medical records were then reviewed for information unable to be obtained through Health Data Compass. The primary objective of the study was to describe CNP treatment at our facility. Descriptive statistics were used to define study population demographics and the primary outcome. Results: A total of 316 patients met study inclusion. The majority of the patients were white (86.7%) and female (67.4%). The most commonly included cancer types were breast (39.4%) and gastrointestinal (35.6%). Patients with all cancer stages were represented in the study. The majority of patients (n = 283) had a diagnosis code of neuropathy on or after the date of their cancer diagnosis; 33 patients had neuropathy documented prior to their cancer diagnosis. The most common CNP management strategies included: opioids only (37.7%), opioids, gabapentin or pregabalin, and an antidepressant (20.3%), opioids and antidepressants (19.6%), or opioids and gabapentin or pregabalin (17.7%). Nearly half of medications used in CNP were not prescribed prior to the patient’s neuropathy diagnosis date (47.3%). Approximately one-third of the patients (33%) had no dose changes from their initial CNP treatment dose. Conclusions: We completed a large single center study to identify the most commonly used medications for CNP treatment. The study included a wide variety of cancer types and all stages. Opioids were the most commonly used medication to treat CNP at UCH. Next steps will be to evaluate the efficacy of opioids compared to other treatment combinations for the management of CNP.

Prescription Pattern of Drugs Used for Neuropathic Pain and Adherence to NeuPSIG Guidelines in Cancer.

Objective:The objective of the present research was to evaluate the prescription pattern of the drugs used in the pharmacological treatment of cancer-related neuropathic pain (CRNP) and to assess the adherence of the physicians to the Neuropathic Pain Special Interest Group (NeuPSIG) Guidelines.Materials and Methods:This was a cross-sectional, observational study where patients who presented to the pain and palliative care outpatient clinic of the tertiary care hospital with CRNP were prospectively recruited. Participants were screened for neuropathic pain using DN4 questionnaire. Demographic details, diagnosis, medication details, and adherence to NeuPSIG guidelines were assessed using a validated questionnaire.Results:Of 300 patients screened, 64% were male and 36% were female, with a mean age of 48.26 ± 13.05 years. The predominant symptoms found were pin-and-needle sensation (99%) followed by tingling sensation (98.66%). The most common diagnosis was head-and-neck cancers (37.3%) followed by bone cancers (17.3%) and lung cancers (15.3%). Among the first-line drugs recommended in NeuPSIG for CRNP, pregabalin (78.7%) was the most common drug prescribed followed by amitriptyline (67%). The most common co-prescribed drugs were acid suppressants drugs (50.7%). Tapentadol, which is not part of the NeuPSIG guidelines, was prescribed on 51 occasions for neuropathic pain. Underdosing was observed in 272 prescriptions. Only 12 prescriptions completely adhered, while 275 had partial, and 13 prescriptions had poor adherence to NeuPSIG guidelines.Conclusion:The most commonly used drugs in the treatment of CRNP were pregabalin and amitriptyline. Most physician partially or did not adhere to the NeuPSIG guideline in the management of CRNP.