Axonal excitability does not differ between painful and painless diabetic or chemotherapy-induced distal symmetrical polyneuropathy in a multi-centre observational study

OBJECTIVE: Axonal excitability reflects ion channel function and it is proposed that this may be a biomarker in painful (versus painless) polyneuropathy. Our objective was to investigate the relationship between axonal excitability parameters and chronic neuropathic pain in deeply phenotyped cohorts with diabetic or chemotherapy induced distal symmetrical polyneuropathy. METHODS: 239 participants with diabetic polyneuropathy were recruited from sites in the UK and Denmark, and 39 participants that developed chemotherapy-induced polyneuropathy were recruited from Denmark. Participants were separated into those with probable or definite neuropathic pain and those without neuropathic pain. Axonal excitability of large myelinated fibres was measured with the threshold tracking technique. The stimulus site was the median nerve and the recording sites were the index finger (sensory studies) and abductor pollicis brevis muscle (motor studies). RESULTS: Participants with painless and painful polyneuropathy were well matched across clinical variables. Sensory and motor axonal excitability measures, including recovery cycle, threshold electrotonus, strength duration time constant, and current-threshold relationship, did not show differences between participants with painful and painless diabetic polyneuropathy, while there were only minor changes for chemotherapy-induced polyneuropathy. INTERPRETATION: Axonal excitability did not significantly differ between painful and painless diabetic or chemotherapy induced polyneuropathy in a multi-centre observational study. Threshold tracking assesses the excitability of myelinated axons; the majority of nociceptors are unmyelinated and although there is some overlap of the 'channelome' between these axonal populations, our results suggest that alternative measures such as microneurography are required to understand the relationship between sensory neuron excitability and neuropathic pain. This article is protected by copyright. All rights reserved

Neuropathy and pain after breast cancer treatment : a prospective observational study

Objectives: Neurological complications including pain are common after treatment for breast cancer. This prospective study investigated the symptoms, intensity and interference of chemotherapy-induced peripheral neuropathy. (CIPN) in the feet and hands compared to surgery- and radiation-induced neuropathy in the breast and upper arm. Methods: Consecutive patients referred to surgery for breast cancer were included in a prospective study and completed a questionnaire at baseline and a follow-up questionnaire and interview after one year. CIPN was assessed with the CIPN20 questionnaire and the Michigan Neuropathy Screening Instrument questionnaire (MNSIq). Pain intensity was rated on a numeric rating scale (NRS, 0-10). Results: In total 144 patients were included, of which 73 received chemotherapy. At one-year follow-up, symptoms of polyneuropathy were more common in patients treated with chemotherapy. Tingling or numbness in the feet in those treated/not treated with chemotherapy was reported by 44 (62%) and 15 (21%), respectively. Pain was present in 22 (30%) and 10 (14%), respectively. Pain in the area of surgery was reported by 66 (46%). Although less common, pain in the feet in those treated with chemotherapy was rated as more intense and with more daily life interference than pain in the surgical area (NRS 5.5 (SD 1.9) vs. 3.1 (SD 1.9). Conclusions: Neurological complications including pain following surgery and chemotherapy represent a burden to breast cancer survivors. In those who had received chemotherapy, pain in the feet was less common than pain in the surgical area, but pain in the feet was more intense and had a higher interference with daily life. Our study emphasizes the need for either baseline data or a control population for improved estimation of the presence and severity of CIPN and pain from questionnaires

Study protocol: fish oil supplement in prevention of oxaliplatin-induced peripheral neuropathy in adjuvant colorectal cancer patients – a randomized controlled trial. (OxaNeuro)

Abstract Background Oxaliplatin-induced peripheral neuropathy (OIPN) in general and painful OIPN in particular is a debilitating late effect that severely affects cancer survivors’ quality of life and causes premature cessation of potentially lifesaving treatment. No preventive treatments and no effective treatment for chronic OIPN exist despite many attempts. One of several suggested mechanisms includes neuroinflammation as a contributing factor to OIPN. Fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs) are precursors to specialized proresolving mediators that mediate the resolution of inflammation. Our primary hypothesis is that a high supplementation of n-3 LCPUFAs will lower the prevalence and severity of OIPN. Methods The OxaNeuro project is an investigator-initiated, multicenter, double-blinded, randomized, placebo-controlled clinical study. We will include 120 patients eligible to receive adjuvant oxaliplatin after colorectal cancer surgery. Patients will receive fish oil capsules containing n-3 LCPUFAs or corn oil daily for 8 months. The primary endpoint is the prevalence of OIPN at 8 months defined as relevant symptoms, including one of the following: abnormal nerve conduction screening, abnormal vibration threshold test, abnormal skin biopsy, or abnormal pinprick test. Additional endpoints include the intensity and severity of OIPN-related neuropathic pain, patient-reported OIPN symptoms, quality of life, mental health symptoms, body composition, and cognitive evaluation. Furthermore, we will evaluate inflammatory biomarkers in blood samples and skin biopsies, including the potential OIPN biomarker neurofilament light protein (NfL) which will be measured before each cycle of chemotherapy. Discussion If readily available fish oil supplementation alleviates OIPN prevalence and severity, it will significantly improve the lives of both cancer survivors and palliative cancer patients receiving oxaliplatin; it will improve their quality of life, optimize chemotherapeutic treatment plans by lowering the need for dose reduction or premature cessation, and potentially increase survival. Trial registration ClinicalTrial.gov identifier: NCT05404230 Protocol version: 1.2, April 25th. 202

Additional file 1 of Study protocol: fish oil supplement in prevention of oxaliplatin-induced peripheral neuropathy in adjuvant colorectal cancer patients – a randomized controlled trial. (OxaNeuro)

Additional file 1: Supplementary Table 1. Overview of trial outcomes in the OxaNeuro project. Supplementary Table 2. Overview of blood samples and preparation. Supplementary Table 3. Appendix 3 Overview of skin biopsies. Supplementary Table 4. List of trial sites. Supplementary Table 5. World Health Organization Trial Registration Data Set

Association of sensory phenotype with quality of life, functionality, and emotional well-being in patients suffering from neuropathic pain

International audienceABSTRACT: Neuropathic pain highly affects quality of life, well-being, and function. It has recently been shown based on cluster analysis studies that most patients with neuropathic pain may be categorized into 1 of 3 sensory phenotypes: sensory loss, mechanical hyperalgesia, and thermal hyperalgesia. If these phenotypes reflect underlying pathophysiological mechanisms, they may be more relevant for patient management than underlying neurological diagnosis or pain intensity. The aim of this study was thus to examine the impact of these sensory phenotypes on mental health, functionality, and quality of life. Data of 433 patients from the IMI/EuroPain network database were analyzed, and results of HADS-D/A, Pain Catastrophizing Scale, Euro Quality of Life 5D/-VAS, Brief Pain Inventory, and Graded Chronic Pain Scale between the sensory phenotypes were compared using multiple regression analysis. There was no difference in chronic pain grade, pain intensity, depression, or anxiety scores between phenotypes. Pain interference (Brief Pain Inventory) was higher (P = 0.002); self-reported health state lower (Euro Quality of Life 5D VAS, P = 0.02); and problems regarding mobility (P = 0.008), usual activities (P = 0.004), and self-care (P = 0.039) more prominent (EQ5-D) in the sensory loss compared with the thermal hyperalgesia phenotype. Patients with sensory loss also showed higher pain catastrophizing scores (P = 0.006 and 0.022, respectively) compared with the 2 other groups. Sensory phenotype is associated with the impact of neuropathic pain conditions on well-being, daily functionality, and quality of life but is less associated with pain intensity. These results suggest that the somatosensory phenotype should be considered for personalized pain management. Copyrigh