Cold aggravates abnormal excitability of motor axons in oxaliplatin‐treated patients

• Published in: Muscle & nerve Vol. 61; no. 6; pp. 796 - 800
• Main Authors: Bennedsgaard, Kristine, Ventzel, Lise, Grafe, Peter, Tigerholm, Jenny, Themistocleous, Andreas C., Bennett, David L., Tankisi, Hatice, Finnerup, Nanna B.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.06.2020; Wiley Subscription Services, Inc
• Subjects: allodynia; Axons; Channel gating; Clinical Research Short Report; Clinical Research Short Reports; Cold; Colorectal cancer; Colorectal carcinoma; Cooling; Cooling effects; Excitability; Motor neurons; nerve excitability testing; neuropathy; Oxaliplatin; oxaliplatin toxicity; Pain; Pain perception; Peripheral nerves; Potassium; potassium channel dysfunction; Potassium channels; Potassium channels (voltage-gated); Refractory period; Sensory testing; Skin temperature; sodium channel dysfunction; Sodium channels (voltage-gated); neuropathy; allodynia; nerve excitability testing; sodium channel dysfunction; oxaliplatin toxicity; potassium channel dysfunction
• DOI: 10.1002/mus.26852
• ISSN: 0148-639X

Introduction Cold allodynia is often seen in the acute phase of oxaliplatin treatment, but the underlying pathophysiology remains unclear. Methods Patients scheduled for adjuvant oxaliplatin for colorectal cancer were examined with quantitative sensory testing and nerve excitability tests at baseline and after the second or third oxaliplatin cycle at different skin temperatures. Results Seven patients were eligible for examination. All patients felt evoked pain and tingling when touching something cold after oxaliplatin infusion. Oxaliplatin decreased motor nerve superexcitability (P < .001), increased relative refractory period (P = .011), and caused neuromyotonia‐like after‐activity. Cooling exacerbated these changes and prolonged the accommodation half‐time. Discussion The findings suggest that a combined effect of oxaliplatin and cooling facilitates nerve excitability changes and neuromyotonia‐like after‐activity in peripheral nerve axons. A possible mechanism is the slowing in gating of voltage‐dependent fast sodium and slow potassium channels, which results in symptoms of cold allodynia.