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

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.