Axonal excitability changes and acute symptoms of oxaliplatin treatment: In vivo evidence for slowed sodium channel inactivation

OBJECTIVE: Neurotoxicity is the most frequent dose-limiting side effect of the anti-cancer agent oxaliplatin, but the mechanisms are not well understood. This study used nerve excitability testing to investigate the pathophysiology of the acute neurotoxicity. METHODS: Questionnaires, quantitative sensory tests, nerve conduction studies and nerve excitability testing were undertaken in 12 patients with high-risk colorectal cancer treated with adjuvant oxaliplatin and in 16 sex- and age-matched healthy controls. Examinations were performed twice for patients: once within 3 days after oxaliplatin treatment (post-infusion examination) and once shortly before the following treatment (recovery examination). RESULTS: The most frequent post-infusion symptoms were tingling paresthesias and cold allodynia. The most prominent nerve excitability change was decreased superexcitability of motor axons which correlated with the average intensity of abnormal sensations (Spearman Rho = 0.80, p < .01). The motor nerve excitability changes were well modeled by a slowing of sodium channel inactivation, and were proportional to dose/m2 with a half-life of about 10d. CONCLUSIONS: Oxaliplatin induces reversible slowing of sodium channel inactivation in motor axons, and these changes are closely related to the reversible cold allodynia. However, further studies are required due to small sample size in this study. SIGNIFICANCE: Nerve excitability data provide an index of sodium channel dysfunction: an objective biomarker of acute oxaliplatin neurotoxicity

To quantum mechanics through random fluctuations at the Planck time scale

We show that (in contrast to a rather common opinion) QM is not a complete theory. This is a statistical approximation of classical statistical mechanics on the {\it infinite dimensional phase space.} Such an approximation is based on the asymptotic expansion of classical statistical averages with respect to a small parameter $\alpha.$ Therefore statistical predictions of QM are only approximative and a better precision of measurements would induce deviations of experimental averages from quantum mechanical ones. In this note we present a natural physical interpretation of $\alpha$ as the time scaling parameter (between quantum and prequantum times). By considering the Planck time $t_P$ as the unit of the prequantum time scale we couple our prequantum model with studies on the structure of space-time on the Planck scale performed in general relativity, string theory and cosmology. In our model the Planck time $t_P$ is not at all the {\it "ultimate limit to our laws of physics"} (in the sense of laws of classical physics). We study random (Gaussian) infinite-dimensional fluctuations for prequantum times $s\leq t_P$ and show that quantum mechanical averages can be considered as an approximative description of such fluctuations.Comment: Discussion on the possibility to go beyond Q

Pain in platin-induced neuropathies: A systematic review and meta-analysis

INTRODUCTION: Platin-induced peripheral neuropathy (PIPN) is a common cause of PN in cancer patients. The aim of this paper is to systematically review the current literature regarding PIPN, with a particular focus on epidemiological and clinical characteristics of painful PIPN, and to discuss relevant management strategies. METHODS: A systematic computer-based literature search was conducted on the PubMed database. RESULTS: This search strategy resulted in the identification of 353 articles. After the eligibility assessment, 282 articles were excluded. An additional 24 papers were identified by scanning the reference lists. In total, 95 papers met the inclusion criteria and were used for this review. The prevalence of neuropathic symptoms due to acute toxicity of oxaliplatin was estimated at 84.6%, whereas PN established after chemotherapy with platins was estimated at 74.9%. Specifically regarding pain, the reported prevalence of pain due to acute toxicity of oxaliplatin was estimated at 55.6%, whereas the reported prevalence of chronic peripheral neuropathic pain in PIPN was estimated at 49.2%. CONCLUSION: Peripheral neuropathy is a common complication in patients receiving platins and can be particularly painful. There is significant heterogeneity among studies regarding the method for diagnosing peripheral neuropathy. Nerve conduction studies are the gold standard and should be performed in patients receiving platins and complaining of neuropathic symptoms post-treatment

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