Contribution of Loss of Large Fiber Function to Pain in 2 Samples of Oncology Patients

Abstract

Numbness associated with neuropathic pain suggests the loss of function in myelinated, large diameter sensory neurons. The purpose of this study was to examine the relationships between pain severity and subjective (i.e., severity of numbness) and objective (i.e., loss of light touch sensations, vibration thresholds) measures of loss of large fiber function in adult survivors with chemotherapy-induced peripheral neuropathy (CIN, n=426) and breast cancer patients with persistent post-surgical pain (n=80). For both samples, average pain and numbness were evaluated using a 0 to 10 numeric rating scale (NRS). Loss of light touch sensations in the hands and feet of patients with CIN and in the upper arm of patients at 5 and 6 months following breast cancer surgery were assessed using Semmes Weinstein monofilaments. Loss of vibration in the hands and feet of patients with CIN was assessed using a biothesiometer. Pearson Product Moment correlation coefficients were calculated between average pain and the number or percentage of sites with loss of light touch sensations, mean vibration thresholds, and the severity of numbness. For both pain conditions, average pain scores were significantly correlated with objective measures of large fiber function (r = 0.12 to 0.34; all, p<.05) and numbness (r = 0.22 to 0.52; all, p<.008). Our findings, in two independent samples of oncology patients, suggest that loss of function of myelinated, large diameter fibers contributes to the severity of neuropathic pain.

CYP3A genetic variation and taxane-induced peripheral neuropathy: a systematic review, meta-analysis, and candidate gene study

“…Our data suggest that development of peripheral neuropathy during chemotherapy is a greater risk in patients who have diabetes in keeping with previous literature (Hershman et al, 2016;Molassiotis et al, 2019). Advanced age has been a reported a risk factor in the literature (Tanabe et al, 2013;Schneider et al, 2015;Bao et al, 2016;Hershman et al, 2016;Tanabe et al, 2017;Bandos et al, 2018;Miaskowski et al, 2018;Molassiotis et al, 2019;Sánchez-Barroso et al, 2019;Hiramoto et al, 2022;Rattanakrong et al, 2022), and our data show a trend towards age being a risk factor, but this was not significant presumably because of a lack of power. Sex was also significantly associated with development of PN: 91% of cases were female.…”

“…Diagnosis, assessment, and management of CIPN is challenging. Key patient characteristics increasing the risk of CIPN (including PN severity and long-duration PN), have been identified (summarised in Table 1), including obesity (Bao et al, 2016;Bandos et al, 2018)/high body mass index (BMI) (Bao et al, 2016;Hiramoto et al, 2022), and advanced age (Tanabe et al, 2013;Schneider et al, 2015;Bao et al, 2016;Hershman et al, 2016;Tanabe et al, 2017;Bandos et al, 2018;Miaskowski et al, 2018;Molassiotis et al, 2019;Sánchez-Barroso et al, 2019;Hiramoto et al, 2022;Rattanakrong et al, 2022), although age has been contested as an independent risk factor (Eckhoff et al, 2015b;Johnson et al, 2015;Barginear et al, 2019;Sánchez-Barroso et al, 2019;Valentine, 2020). Multimorbidity/co-morbidity (Loprinzi et al, 2007;Lavoie Smith et al, 2011;Reeves et al, 2012;Tanabe et al, 2013;de la Morena Barrio et al, 2015;Bao et al, 2016;Fernandes et al, 2016;Hershman et al, 2016;Molassiotis et al, 2019) is a further risk factor.…”

Duloxetine prevents bortezomib and paclitaxel large-fiber chemotherapy-induced peripheral neuropathy (LF-CIPN) in sprague dawley rats

“…Since there are currently few preclinical models of LF-CIPN available, 16,17 we first developed a model using the response to selective large-fiber activation with high frequency electrical stimulation of the rat’s tail, referred to in the literature as the Current Perception Threshold (CPT) protocol. 18 Our results demonstrate that Bortezomib and Paclitaxel, whose anti-cancer mechanisms are quite different, 26 but that can both cause large-fiber neuropathy in patients, 27 produce an elevation of CPT in the rat, supporting the suggestion that Bortezomib and Paclitaxel cause loss of large-fiber function. Since the CPT protocol selectively activates large-fibers, and does not therefore produce pain, it is possible that this technique could be used as a biomarker for the study of large-fiber CIPN in oncology patients receiving neurotoxic chemotherapy drugs as well as to objectively evaluate the response of LF-CIPN to Duloxetine and potentially other treatment modalities.…”