Electroacupuncture improves peripheral neuropathy by up-regulating Sirt1/PGC-1α/TFAM pathway in type 2 diabetes rats with peripheral neuropathy. / 基于Sirt1/PGC-1α/TFAM通路探讨电针治疗2åž‹ç³–å°¿ç— å‘¨å›´ç¥žç»ç— å˜çš„æœºåˆ¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on activation of silent information regulator 1 (Sirt1)/peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway in type 2 diabetes (T2DM) rats with peripheral neuropathy (DPN) , so as to explore its possible mechanisms underlying improvement of DPN. METHODS: Thirty male SD rats were randomly divided into blank control group (n=8) and DPN model group (n=22) which were further divided into model group (n=8) and EA group (n=8) after successful modeling. The model of T2DM was established by high-fat diet and low-dose intraperitoneal injection of streptozocin (35 mg/kg). For rats of the EA group (anesthetized with isoflurane), EA stimulation (2 Hz/15 Hz, 2 mA) was applied to "Tianshu"(ST25) for 20 min, once daily, 6 times a week for 6 weeks. The blood glucose level, body weight, area under curve (AUC) of glucose tolerance test, and hind-paw mechanical pain threshold and thermal pain threshold were observed. The intra-epidermal nerve fiber density (IENFD) of the hind-foot pad was observed by immunofluorescence staining. The motor nerve conduction velocity (MNCV) of the sciatic nerve was measured by using electrophysiological method. H.E. staining was used to observe the histopathological changes of the sciatic nerve after modeling. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes of the sciatic nerve. The protein expressions of energy-related Sirt1, PGC-1α and TFAM in the sciatic nerve was detected by Western blot. RESULTS: Compared with the blank control group, the model group had a higher blood glucose contents and AUC (P<0.001), a slower MNCV (P<0.01), and a decrease in the body weight and in the mechanical and thermal pain thresholds (P<0.001) and IENFD (P<0.001), and in the expression levels of Sirt1, PGC-1α and TFAM (P<0.05, P<0.01). In contrast to the model group, the EA group had a decrease in the blood glucose contents and AUC (P<0.05, P<0.01), and an increase in mechanical and thermal pain thresholds, MNCV, IENFD, and expression levels of Sirt1, PGC-1α and TFAM proteins (P<0.01, P<0.05). In addition, results of histopathological and ultrastructural changes of the sciatic nerve showed more fragmented and disordered distribution of axons on the transverse section, and extensive separation of myelin and axons, uneven myelin thickness, axonal degeneration and irregular shape in the model group, whereas in the EA group, the axons on the transverse section were relatively more dense and more complete, the myelin sheath of the sciatic nerve was relatively uniform, and the axonal shape was relatively regular with relatively milder lesions. CONCLUSIONS: EA up-regulates the expressions of Sirt1, PGC-1α, TFAM in T2DM rats with DPN, which may be associated with its functions in improving and repairing the injured peripheral nerves in rats with DPN.

Multimodal Approaches in the Treatment of Chronic Peripheral Neuropathy-Evidence from Germany.

Patients with chronic peripheral neuropathy suffer greatly and their quality of life is often restricted. Drug therapy can be accompanied by undesirable side effects and intolerances, or the hoped-for effect does not materialize. Therefore, in addition to drug therapy, attempts are also made to treat the physical symptoms with complementary procedures. In the case of severe forms, the search for a suitable form of therapy is difficult. Complex treatments can be an innovative way to treat peripheral neuropathy. At the same time, several different therapy methods are carried out at high frequency by a specialized treatment team. This study aimed to provide an overview of possible complementary forms of therapy. The focus was on a comparison of two interdisciplinary complex therapies that are used in severe cases in an acute inpatient care setting in Germany. The six dimensions (energy, sleep, pain, physicality, emotional response and social isolation) of the Nottingham Health Profile (NHP) were used to assess quality of life. Both complex treatments (naturopathic complex therapy/multimodal pain therapy) showed a significant reduction in impairment in all dimensions of the NHP. In addition, a multivariate analysis was carried out to take into account several influencing variables at the same time. At the time of admission to the hospital, the degree of chronicity was recorded for each patient. This allowed statements to be made about the effect of the respective therapy depending on the chronification stage of the patient. It has been shown that patients with acutely exacerbated pain with the highest degree of chronicity also benefit from both complex treatments. The naturopathic complex treatment gives the treatment team more options. Aspects such as nutrition, methods from phytotherapy and traditional Chinese medicine can be integrated into inpatient care. Thus, a patient-centered, holistic therapy can take place. However, an interdisciplinary holistic therapy requires more time for both the practitioner and the patient. This should be taken into account in the health systems in the context of the diagnosis related groups.

Electroacupuncture use for treatment of taxane-induced peripheral neuropathy in patients with breast cancer: protocol for a pilot, randomised, blinded, sham-controlled trial (EA for CIPN).

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of neurotoxic chemotherapy. Acute symptoms of CIPN during treatment can lead to dose reduction and cessation. Trials using electroacupuncture (EA) to treat established CIPN postchemotherapy have shown some efficacy. The current trial aims to assess the feasibility and preliminary efficacy of using EA to treat CIPN during chemotherapy. METHODS AND ANALYSIS: The current study is a single-centre, 1:1 randomised, sham-controlled pilot study set in a tertiary cancer hospital in Sydney, Australia, and will recruit 40 adult patients with early breast cancer undergoing adjuvant or neoadjuvant paclitaxel chemotherapy. Patients who develop CIPN within the first 6 weeks of chemotherapy will receive either true EA or sham-EA once a week for 10 weeks. The coprimary endpoints are recruitment and adherence rate, successful blinding of patients and compliance with the follow-up period. Secondary endpoints are mean change of CIPN symptoms from randomisation to end of treatment, sustained change in CIPN symptoms at 8-week and 24-week follow-up postchemotherapy, proportion of subjects attaining completion of 12 weeks of chemotherapy without dose reduction or cessation, change in acupuncture expectancy response pretreatment, during treatment and posttreatment. The primary assessment tool for the secondary endpoints will be a validated patient-reported outcome measure (European Organisation for Research and Treatment of Cancer Quality of Life Chemotherapy-Induced Peripheral Neuropathy) captured weekly from randomisation to week 12 of chemotherapy. ETHICS AND DISSEMINATION: The study protocol (2021/ETH12123) has been approved by the institutional Human Research Ethics Committee at St Vincent's Hospital Sydney and Chris O'Brien Lifehouse. Informed consent will be obtained prior to starting study-related procedures. The results will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000081718.

Complementary and alternative medicine in relation to chemotherapy-induced peripheral neuropathy: A narrative review.

PURPOSE: To summarizes the available evidence on the effectiveness, safety, and feasibility of complementary and alternative medicine (CAM) in the management of chemotherapy-induced peripheral neuropathy (CIPN). METHODS: We searched for systematic reviews, and meta-analyzes published up to April 2023 in the Pubmed and Web of Science databases. The latest original research on related topics was also reviewed. The search was restricted to English-language papers. Two independent reviewers performed a quality assessment of the identified literature. RESULTS: The results of 35 systematic reviews and meta-analyzes were included in this study. Preliminary evidence suggests that CAM, including acupuncture, physical activity (PA), herbal and nutritional supplements, mind-body therapies, touch therapy, and non-invasive neuromodulation techniques, have shown tremendous potential for the prevention and treatment of CIPN. Of these, there is strong evidence supporting acupuncture, PA, and herbal medicine. However, existing clinical studies are also limited by the heterogeneity of study methods, insufficient sample size, and poor study design. Further studies are needed to validate the efficacy of CAM in patients with CIPN and to elucidate potential therapeutic mechanisms. CONCLUSIONS: Current research has reached a preliminary conclusion suggesting the potential efficacy of certain CAMs in the management of CIPN. Future clinical trials should incorporate more robust study design protocols and larger sample sizes to enhance the validity of findings.

The Efficacy of Acupuncture in the Treatment of Chemotherapy-Induced Peripheral Neuropathy: A Network Meta-Analysis.

Background: Chemotherapy-induced peripheral neuropathy (CIPN), one of the most common adverse events associated with chemotherapy, may affect efficacy because of the interruption of chemotherapy or change of regimen in severe cases, and may even increase cancer mortality. Relevant data supports the evidence that acupuncture can treat pain and sensory abnormalities. However, choosing the most effective acupuncture therapy is difficult because of the lack of evidence-based medicine and comparisons between different acupuncture therapies for treating CIPN. The aim of this study was to use a network meta-analysis (NMA) to evaluate the efficacy of different acupuncture therapies for CIPN. Methods: We searched Embase, PubMed, Web of Science, The Cochrane Library, The Chinese Journal Full Text Database, Chinese Biomedical Literature Database, and WanFang Database for randomized controlled trials (RCTs) of acupuncture for CIPN. The search period was from the creation of the relevant library to August 10, 2023. A total of 2 investigators independently performed literature screening, data extraction, and risk for bias evaluation. Stata 14.0 software (StataCorp LLC, College Station, Texas USA), was used for the NMA. Results: A total of 13 eligible RCTs involving 746 patients and 6 acupuncture therapies were included in the study. The NMA results showed that electroacupuncture was superior to moxibustion, manual acupuncture, acupoint injection and Western medicine in improving the total effective rate of treatment of CIPN; electroacupuncture + moxibustion was better than manual acupuncture, acupoint injection, and Western medicine. Manual acupuncture's total effective rate was better than Western medicine. However, electroacupuncture was the most effective treatment for CIPN according to the surface under the cumulative ranking curve (SUCRA) ranking. Conclusion: After a comprehensive evaluation of 6 acupuncture therapies for treating CIPN based on NMA, electroacupuncture may be the best option for treating CIPN. However, would be more convincing to get evidence from more RCTs.

An umbrella review of the evidence to guide decision-making in acupuncture therapies for chemotherapy-induced peripheral neuropathy.

BACKGROUND: Acupuncture therapy is believed to have therapeutic potential for patients suffering from chemotherapy-induced peripheral neuropathy (CIPN). This umbrella review aims to summarize and evaluate the evidence from current systematic reviews/meta-analyses (SRs/MAs) on the effectiveness of acupuncture treatment for CIPN. METHODS: We conducted a comprehensive search in eight electronic databases for SRs/MAs that included RCTs on acupuncture treatment for CIPN. Two separate researchers independently evaluated the methodological quality, reporting quality, and evidence quality of the SRs/MAs that were included in the study. Additionally, we examined the extent of overlap among the included RCTs by calculating the corrected covered area (CCA). Furthermore, we assessed the dependability of the effect sizes by conducting excess significance tests. We conducted a quantitative synthesis of all RCTs included in the SRs/MAs to obtain objective and updated conclusions. Furthermore, we also conducted an analysis of the acupuncture points used in RCTs. RESULTS: This umbrella review includes 9 SRs/MAs, and their methodological quality, risk of bias, reporting quality, and evidence quality were all deemed unsatisfactory. Out of the 9 SRs/MAs, 28 RCTs were included, with a total CCA of 25.4%, indicating a high degree of overlap. The test of super-significance did not yield any significant results. Our updated meta-analysis suggests that CIPN patients can benefit from acupuncture therapy, as indicated by effectiveness in measures including BPI-SF, VAS, FACT-NTX, NRS, SCV, and NCI-CTCAE. Egger's test and sensitivity analysis demonstrate the reliability and stability of this conclusion. The commonly used acupuncture points in the current RCTs include ST36, LI11, LI4, LR3, and SP6. CONCLUSION: Based on the existing evidence, acupuncture is effective and safe for patients with CIPN, as it can significantly improve effective rate, pain symptoms, quality of life, and nerve conduction velocity. However, given the low quality of current evidence, we should be cautious in interpreting this conclusion.

A Randomized Sham-Controlled Mixed Methods Pilot Study of the Feasibility of Acupuncture for Chemotherapy-Induced Neuropathy: Lessons Learned From Patient Experiences in Integrative Cancer Care.

OBJECTIVE: Since there is a lack of effective pharmacological therapies for chemotherapy-induced neuropathy and many patients ask for integrative cancer therapies such as acupuncture, the objective of this pilot study was to describe patients' experiences, and to study the feasibility and short-term effects of genuine acupuncture for chemotherapy-induced neuropathic pain and unpleasant sensations compared to sham acupuncture. METHODS: The pilot study used mixed methods, collecting quantitative and qualitative data. Patients (n = 12) with chemotherapy-induced neuropathy after colorectal cancer were blindly randomized to genuine acupuncture or telescopic sham acupuncture. Individual interviews were conducted, and were analyzed using qualitative content analysis. The patients registered pain and unpleasant sensations (100 mm Visual Analog Scales) before and after n = 120 sessions, n = 60 genuine and n = 60 sham acupuncture sessions. RESULTS: Five categories of patient experiences were described. The neuropathy negatively affected life. Physical activity was perceived to be important for health, but neuropathy was a barrier. The neuropathy required symptom-managing strategies. Acupuncture was pleasant and valuable, but some patients presented doubts regarding its effect mechanisms. After the genuine acupuncture sessions, pain (mean -2.0 steps relief during each session) and unpleasant sensations (-2.4) in the face was reduced more than after sham acupuncture (+0.1 steps worse pain, P = .018, +0.1 steps worse unpleasant sensations, P = .036). After genuine acupuncture, unpleasant sensations in the hands were reduced less (-0.23) compared to after sham acupuncture (-5.5, P = .002). Pain or unpleasant sensations in the feet did not change. CONCLUSIONS: Patients experienced that the neuropathy negatively changed their life and that acupuncture was pleasant and valuable. Patients receiving genuine acupuncture had short-term effects regarding pain and unpleasant sensations in the face compared to patients receiving sham acupuncture, while hands and feet did not improve. The patients were successfully blinded and complied with the acupuncture. We welcome future full-scaled randomized sham-controlled acupuncture studies.

Hyperbaric Oxygen Therapy Alleviates Paclitaxel-Induced Peripheral Neuropathy Involving Suppressing TLR4-MyD88-NF-κB Signaling Pathway.

Paclitaxel (PAC) results in long-term chemotherapy-induced peripheral neuropathy (CIPN). The coexpression of transient receptor potential vanilloid 1 (TRPV1) and Toll-like receptor 4 (TLR4) in the nervous system plays an essential role in mediating CIPN. In this study, we used a TLR4 agonist (lipopolysaccharide, LPS) and a TLR4 antagonist (TAK-242) in the CIPN rat model to investigate the role of TLR4-MyD88 signaling in the antinociceptive effects of hyper-baric oxygen therapy (HBOT). All rats, except a control group, received PAC to induce CIPN. Aside from the PAC group, four residual groups were treated with either LPS or TAK-242, and two of them received an additional one-week HBOT (PAC/LPS/HBOT and PAC/TAK-242/HBOT group). Mechanical allodynia and thermal hyperalgesia were then assessed. The expressions of TRPV1, TLR4 and its downstream signaling molecule, MyD88, were investigated. The mechanical and thermal tests revealed that HBOT and TAK-242 alleviated behavioral signs of CIPN. Immunofluorescence in the spinal cord dorsal horn and dorsal root ganglion revealed that TLR4 overexpression in PAC- and PAC/LPS-treated rats was significantly downregulated after HBOT and TAK-242. Additionally, Western blots showed a significant reduction in TLR4, TRPV1, MyD88 and NF-κB. Therefore, we suggest that HBOT may alleviate CIPN by modulating the TLR4-MyD88-NF-κB pathway.

Efficacy and safety of electroacupuncture for oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: a single-blinded, randomized, sham-controlled trial.

BACKGROUND: Oxaliplatin-based chemotherapy is a major first-line conventional therapy for advanced and metastatic colorectal cancer (CRC). However, oxaliplatin causes chemotherapy-induced peripheral neuropathy (CIPN). Acupuncture has long been used to alleviate limb numbness in Chinese medicine practice. AIM: The aim of this study was to examine the efficacy and safety of electroacupuncture (EA) for the alleviation of CIPN in CRC patients. DESIGN: This was a pilot single-blinded, randomized, sham-controlled trial. SETTING/PARTICIPANTS: Sixty eligible patients, who had been diagnosed with CRC and were undergoing oxaliplatin-based chemotherapy, were randomized in a ratio of 1:1 to the EA intervention group or sham acupuncture (SA) control group. During a 12-week treatment period, patients in the EA group received EA once a week, while patients in the SA group received SA; both groups were followed up for 12 weeks. RESULTS: Compared with the SA group, the EA group exhibited significant alleviation of CIPN severity during chemotherapy. Moreover, EA also improved the physical function, role function, and social function of CRC patients. However, there were no significant differences in tests of vibration or light touch sensation. In addition, EA appeared to be a safe treatment for CIPN and was both feasible and acceptable to CRC patients during chemotherapy. CONCLUSION: This study showed preliminary evidence for the efficacy and safety of EA in acute CIPN among CRC patients, although further studies are needed to verify these effects and to further explore the potential role of EA in chronic CIPN (effects on which remain unclear). TRIAL REGISTRATION NUMBER: NCT03582423 (ClinicalTrials.gov).

Data mining analysis reveals key acupoints and meridians for the treatment of chemotherapy-induced peripheral neuropathy.

OBJECTIVE: To explore effective acupoints and combinations for the treatment of chemotherapy-induced peripheral neuropathy (CIPN) METHODS: Clinical controlled trials and randomized controlled trials of acupuncture for CIPN were sourced from PubMed, Embase, Web of Science, and Chinese databases, including the Wanfang database, VIP Journals database, and China National Knowledge Infrastructure database. The quality of eligible research was evaluated based on CONSORT and STRICTA statements. The common acupoints, meridians, and acupoint combinations were determined from acupuncture prescriptions reporting positive effects and were analyzed using SPSS 23.0 and SPSS Modeler 14.1. Finally, a complex network was constructed using Cytoscape 3.8.2 to explore the core acupoints. RESULTS: The quality of 24 clinical trials was evaluated, and 20 acupuncture prescriptions that reported positive outcomes were included in subsequent data mining analysis. The most frequently used acupoints are ST36, LI11, LI4, LR3, and SP6. Meanwhile, they are also the core acupoints in acupuncture prescriptions according to the complex network with 28 nodes and 177 edges. The most commonly used meridians were the large intestine, stomach, and spleen. Acupoint combinations of LI11 and ST36, SP6 and ST36 were frequently used. CONCLUSION: Our study provides a reference for the selection of effective acupoints for CIPN treatment and a basis for the effective use of this form of traditional Chinese medicine. Furthermore, we found limitations in the design and implementation of the available clinical research, which should be minimized in future studies.

A randomized pilot study of oncology massage to treat chemotherapy-induced peripheral neuropathy.

This pilot randomized controlled trial investigated massage therapy for symptomatic relief of chemotherapy-induced peripheral neuropathy (CIPN) to determine the ideal weekly frequency and number of weeks of providing massage. We evaluated the feasibility and initial efficacy of a Swedish massage protocol to treat lower extremity (LE) CIPN. Inclusion criteria: LE neuropathy attributed to oxaliplatin, paclitaxel, or docetaxel, with no other attributable causes; ≥ 6 months since last chemotherapy; self-reported neuropathy score ≥ 3, 0-10 scale; age ≥ 18. Participant randomization (2:2:1:1) to one of four groups: LE (2) or head/neck/shoulder (control; 1) massage 3 times (3X) a week for 4 weeks; LE (2) or control (1) massage 2X/week for 6 weeks. Completion rate and the Pain Quality Assessment Scale (PQAS) was measured at baseline and 10 weeks later. 71 patients participated: 77.5% women; 57.7% (breast cancer), and 42.3% (GI cancer); mean age 60.3 y/o (range: 40-77); average > 3 years since last chemotherapy. Massage was deemed feasible: mean completion rates (max = 12) were 8.9 (SD 4.2) for 3X/week and 9.8 (SD 4.0) for 2X/week with no statistically significant differences. There were no statistically significant treatment group interactions in PQAS scores at 10-weeks follow-up. There was a statistically significant treatment schedule main effect for PQAS subscales (p < 0.05) at 10 weeks, with lower CIPN symptoms for 3X/week groups versus 2X/week groups. Improvements considered clinically significant favored the LE 3X/week group. Completion rates met pre-defined feasibility criteria. We seemed to observe better outcomes (CIPN symptom reduction) with the more intensive (3X/week for 4 weeks) massage intervention with no differences in adherence, regardless of whether the massage was directly to the CIPN-affected area or not. However, there was some suggestion that the massage program targeting the CIPN-affected area directly provided 3X a week for 4 weeks resulted in the best outcomes.

Impact of acupuncture and integrative therapies on chemotherapy-induced peripheral neuropathy: A multicentered, randomized controlled trial.

BACKGROUND: To explore the impact of acupuncture with other complementary and integrative medicine (CIM) modalities on chemotherapy-induced peripheral neuropathy (CIPN) and quality of life (QoL) in oncology patients. METHODS: In this prospective, pragmatic, and patient-preference study, patients with CIPN were treated with acupuncture and CIM therapies (intervention group) or standard care alone (controls) for 6 weeks. Patients in the intervention arm were randomized to twice-weekly acupuncture-only (group A) or acupuncture with additional manual-movement or mind-body CIM therapies (group B). Severity of CIPN was assessed at baseline and at 6 weeks using the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) tool. Other QoL-related outcomes were assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC); and the Measure Yourself Concerns and Well-being questionnaire. Von Frey measurements examined perception thresholds. RESULTS: Of 168 participants, 136 underwent the study intervention (group A, 69; group B, 67), with 32 controls. Baseline-to-6-week assessment scores improved significantly in the intervention arm (vs controls) on FACT-Tax (p = .038) and emotional well-being (p = .04) scores; FACT-TAX scores for hand numbness/tingling (p = .007) and discomfort (p < .0001); and EORTC physical functioning (p = .045). Intervention groups A and B showed improved FACT-Tax physical well-being (p < .001), FACT-TAX total score (p < .001), FACT-TAX feet discomfort (p = .003), and EORTC pain (p = .017) scores. CONCLUSIONS: Acupuncture, with or without CIM modalities, can relieve CIPN-related symptoms during oncology treatment. This is most pronounced for hand numbness, tingling, pain, discomfort, and for physical functioning.

Effectiveness of the online Acceptance and Commitment Therapy intervention "Embrace Pain" for cancer survivors with chronic painful chemotherapy-induced peripheral neuropathy: study protocol for a randomized controlled trial.

BACKGROUND: About 30% of cancer survivors suffer from chemotherapy-induced peripheral neuropathy (CIPN) ≥6 months after completion of chemotherapy. This condition, for which treatment options are scarce, comes with limitations in daily life functioning and decreased quality of life. The current study examines the effectiveness of an online self-help intervention based on Acceptance and Commitment Therapy (ACT) in comparison to a waiting list condition (WLC) to deal with CIPN. In addition, it examines which factors moderate effects and to what extent the effects differ between guided and unguided ACT intervention. METHODS: A two-parallel, non-blinded randomized controlled trial (RCT) will be carried out. Adult cancer survivors who experience painful CIPN for at least 3 months and completed chemotherapy at least 6 months ago will be recruited (n=146). In the intervention condition, participants will follow an 8-week self-management course containing 6 modules regarding psychoeducation and ACT processes, including therapeutic email guidance. By means of text and experiential exercises, supplemented with illustrations, metaphors, and audio files, people will learn to carry out value-oriented activities in their daily life with pain. Participants will learn new ways of coping with pain, including reducing pain avoidance and increasing pain acceptance. Participants in the WLC will be invited to follow the intervention without therapeutic guidance 5 months after start. Pain interference is the primary outcome, while psychological distress, quality of life, CIPN symptom severity, pain intensity, psychological flexibility, mindfulness skills, values-based living, and pain catastrophizing will serve as secondary outcomes. All outcome measures will be evaluated at inclusion and baseline, early-intervention, mid-intervention, post-treatment, and 3- and 6-month post-treatment. Qualitative interviews will be conducted post-treatment regarding experiences, usage, usability, content fit, and satisfaction with the intervention. DISCUSSION: This study will provide valuable information on the effectiveness of an online self-help intervention based on ACT versus WLC for chronic painful CIPN patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT05371158 . Registered on May 12, 2022. PROTOCOL VERSION: version 1, 24-05-2022.

Cancer Survivors' Perspectives of Virtual Yoga for Chronic Chemotherapy-Induced Peripheral Neuropathy Pain During the COVID-19 Pandemic.

With the rise in telehealth due to the COVID-19 pandemic, further research is needed to determine how to optimize virtual delivery of existing integrative oncology interventions for cancer treatment-related symptoms. The purpose of this qualitative analysis was to explore cancer survivors' perspectives of the acceptability and satisfaction of an 8-week, virtual yoga intervention for cancer survivors with chronic chemotherapy-induced peripheral neuropathy pain. Fourteen participants with chronic chemotherapy-induced peripheral neuropathy pain who completed the virtual yoga intervention were interviewed using a semistructured interview guide. Themes were derived from the data using inductive content analysis methods. Main findings from the interviews included the following: (1) participants were willing to try new nonpharmacological treatments for chemotherapy-induced peripheral neuropathy due to the high symptom burden and prior lack of success with medications; (2) participants highly rated the flexibility offered by the virtual format, but desired the social support potentially offered by practicing in-person yoga; and (3) the impact of virtual yoga on chemotherapy-induced peripheral neuropathy severity was unclear. There were several barriers to participants' use of virtual yoga for chronic chemotherapy-induced peripheral neuropathy pain (eg, technology, lack of space/equipment). The results may be used to improve the design and delivery of future trials testing virtual yoga for chronic chemotherapy-induced peripheral neuropathy pain.

A randomised, pragmatic clinical trial of ACUpuncture plus standard care versus standard care alone FOr Chemotherapy Induced peripheral Neuropathy (ACUFOCIN).

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose limiting toxicity posing a major clinical challenge for managing patients receiving specific chemotherapy regimens (e.g., Taxanes). There is a growing body of literature suggesting acupuncture can improve CIPN symptoms. The purpose of the ACUFOCIN trial was to collect preliminary data on the safety, feasibility, acceptability and initial effectiveness of acupuncture as a treatment for CIPN, comparing use of acupuncture plus standard care (Acupuncture) against standard care alone (Control). METHOD: At a tertiary cancer centre, a pragmatic, randomised, parallel group design study was used to investigate the effectiveness of a 10-week course of acupuncture. Participants experiencing CIPN of ≥ Grade II, recording a 'Most Troublesome' CIPN symptom score of ≥3 using the "Measure Yourself Medical Outcome Profile" (MYMOP 2), were randomised to 'Acupuncture' or 'Control' arms. Clinicians were blinded to allocated groups, however as it was not possible to blind participants, it cannot be guaranteed they did not disclose study allocation within their clinic assessments. The primary outcome measure was the number of patients reporting a ≥ 2-point improvement (success) in their MYMOP2 score at week 10. 100 participants (120 to allow for attrition) were required for a hypothesised improvement in success proportions from 30% to 55% using a primary analysis model with logistic regression adjusted for stratification factors and baseline MYMOP2 scores. Feasibility and acceptability of study design was addressed through percentage return of primary outcome, retention rate and a nested qualitative study. RESULTS: Primary MYMOP2 outcome data at week 10 was available for 108/120 randomised participants; this is greater than the 100 participants required to adequately power the study. There were 36/53 (68%) successes in 'Acupuncture' compared to 18/55 (33%) in 'Control'. Beneficial effects were seen in the secondary outcome data, including clinicians' grading of neuropathy, EORTC, QLQ-CIPN20, QLQ-C30 summary scores and patient reported pain scores. There were no serious adverse events reported within the study and only 16 acupuncture associated events, none of which required intervention. CONCLUSION: A 10-week course of acupuncture resulted in measurable improvement in participants symptoms of CIPN. The results warrant further investigation.

Evaluating the safety, feasibility, and efficacy of non-invasive neuromodulation techniques in chemotherapy-induced peripheral neuropathy: A systematic review.

PURPOSE: This systematic review was conducted to evaluate the best available evidence regarding the use of non-invasive neuromodulation techniques for managing chemotherapy-induced peripheral neuropathy (CIPN). METHODS: A systematic literature search of the following databases from their inception to October 17, 2021 was performed and was updated on March 2, 2022: AMED via Ovid, CINAHL via the EBSCO Host, Cochrane Library, Embase, PEDro, PubMed, and Web of Science. Randomized controlled trials (RCTs) and quasi-experimental studies examining the safety, feasibility, and efficacy of non-invasive neuromodulation techniques for managing established CIPN were identified. Narrative synthesis was used to analyze data collected from the included studies. RESULTS: Nine RCTs and nine quasi-experimental studies were included. A variety of non-invasive peripheral and central neuromodulation techniques were investigated in those studies, including scrambler therapy, electrical stimulations, photobiomodulation, magnetic field therapy, therapeutic ultrasound, neurofeedback, and repetitive transcranial magnetic stimulation. Non-invasive neuromodulation techniques for the management of established CIPN are generally safe and feasible. The efficacy of peripheral neuromodulation techniques such as scrambler therapy and transcutaneous electrical nerve stimulation was mostly unsatisfactory, while central neuromodulation techniques such as neurofeedback and repetitive transcranial magnetic stimulation were promising. CONCLUSIONS: The use of non-invasive neuromodulation techniques for managing CIPN is still in its infancy. Non-invasive central neuromodulation techniques have significant potential for relieving chronic pain and neuropathic symptoms related to CIPN, meriting further exploration.

Effects of Transcutaneous Electrical Nerve Stimulation on Pain and Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Systematic Review.

Transcutaneous electrical nerve stimulation (TENS) is the usage of a mild electrical current through electrodes that stimulate nerves. Patients with malignancies experience pain and chemotherapy-induced peripheral neuropathy. A systematic review was performed to find research evaluating the effect of TENS on these two common symptoms decreasing the quality of life in cancer patients. PubMed, the Cochrane Central Register of Controlled Trials and EMBASE were searched. Original studies, namely randomized controlled trials, quasi-randomized controlled trials and controlled clinical trials, published between April 2007 and May 2020, were considered. The quality of the selected studies was assessed. Seven papers were incorporated in a qualitative synthesis, with 260 patients in total. The studies varied in terms of design, populations, endpoints, quality, treatment duration, procedures and follow-up period. Based on the results, no strict recommendations concerning TENS usage in the cancer patient population could be issued. However, the existing evidence allows us to state that TENS is a safe procedure that may be self-administered by the patients with malignancy in an attempt to relieve different types of pain. There is a need for multi-center, randomized clinical trials with a good methodological design and adequate sample size.

Treatment and diagnosis of chemotherapy-induced peripheral neuropathy: An update.

When peripheral neuropathy occurs due to chemotherapy treatment, it is referred to as chemotherapy-induced peripheral neuropathy (CIPN). Typically, symptoms are sensory rather than motor and include reduced feeling and heightened sensitivity to pressure, pain, temperature, and touch. The pathophysiology of CIPN is very complex, and it involves multiple mechanisms leading to its development which will be described specifically for each chemotherapeutic class. There are currently no approved or effective agents for CIPN prevention, and Duloxetine is the only medication that is an effective treatment against CIPN. There is an unavoidable necessity to develop preventative and treatment approaches for CIPN due to its detrimental impact on patients' lives. The purpose of this review is to examine CIPN, innovative pharmacological and nonpharmacological therapy and preventive strategies for this illness, and future perspectives for this condition and its therapies.

Nutraceuticals and peripheral glial cells: a possible link?

A nutraceutical is a food-derived molecule that provides medical or health benefits beyond its basic nutritional role, including the prevention and treatment of disease and its symptoms. In the peripheral nervous system, satellite glial cells are found in close relationship with neurons, mainly in peripheral sensory ganglia, but, compared with other glial cells, the relationship between these cells and nutraceuticals has received little attention. After describing satellite glial cells and their role and changes in physiology and pathology, we review the studies on the effects of nutraceuticals as modulators of their functions. Maybe due to the difficulties in selectively labeling these cells, only a few studies, performed mainly in rodent models, have analyzed nutraceutical effects, showing that N-acetylcysteine, curcumin, quercetin, osthole and resveratrol may palliate neuropathic pain through satellite glial cells-dependent pathways, namely antioxidant mechanisms and/or interference with purinergic signaling. Neither other conditions in which satellite glial cells are involved (visceral pain, nerve regeneration) nor other nutraceuticals or mechanisms of action have been studied. Although more preclinical and clinical research is needed, the available reports support the general notion that nutraceuticals may become interesting alternatives in the prevention and/or treatment of peripheral gliopathies and their associated conditions, including those affecting the satellite glial cells.

Acupuncture for chemotherapy-induced peripheral neuropathy: a randomised controlled pilot study.

Chemotherapy-induced peripheral neuropathy (CIPN) can cause loss of independence and poor quality of life (QoL) due to severe disabilities, but in spite of its importance there is still a lack of data for the management of CIPN. Acupuncture has showed promising results and may be a cost-effective option for the treatment. OBJECTIVES: To evaluate the effect of acupuncture treatment on neurological symptoms of CIPN and QoL of oncological patients. METHODS: We performed a clinical, single-centre, randomised and controlled pilot study that involved 33 adult patients with cancer and CIPN randomised into two groups (control and acupuncture treated with 10 sessions, two times per week). Both groups were subjected to a complete physical examination and clinical assessment with National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Scale V.2.0, FIM Scale, European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Scale and Visual Analogue Scale for pain before and 5 weeks after treatment. RESULTS: There were no adverse events, and we found statistical differences in groups in physical (p=0.03) and function (p=0.04) domains of EORTC QLQ-C30 when comparing control and acupuncture groups. About NCI CTCAE Scale and neuropathy sensory symptoms, we found better results in acupuncture group, comparing pretreatment and post-treatment analyses (p=0.01). In control group, we have no differences after 5 weeks (p=0.11). CONCLUSION: Although these results suggest an interesting effect of acupuncture on this patient population, the clinical significance has remained unclear. Given the tendency towards benefit and the lack of adverse effects, the authors recommend a follow-up acupuncture trial using higher follow-up time and better sample size. TRIAL REGISTRATION NUMBER: NCT02309164.