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

Abstract

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.

Keywords: allodynia; nerve excitability testing; neuropathy; oxaliplatin toxicity; potassium channel dysfunction; sodium channel dysfunction.

Figure 1

Nerve excitability testing for the motor nerve. A) Strength‐duration time constant, B) threshold electrotonus, and C) recovery cycle. Dark line: baseline; gray line: follow‐up without cooling; blue (triangle) line: follow‐up with cooling. Filled lines: means; dashed lines: standard errors [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Afterpotentials after maximum CMAP at baseline, follow‐up, and follow‐up with cooling. The number of afterpotentials increased with cooling. Only six of the seven patients are shown due to excess voluntary activity in one patient. CMAP, compound muscle action potential; OXP, oxaliplatin