There is a limited understanding of the mechanisms that cause diabetic neuropathy. This study showed that increased concentrations of methylglyoxal — production of which is enhanced by elevated glucose concentrations — may be involved in metabolic hyperalgesia. After demonstrating that individuals with diabetic neuropathy had high methylglyoxal concentrations, the authors showed that methylglyoxal caused post-translational modifications of the Nav1.8 sodium channel that were associated with increased firing of nociceptive neurons. In mouse models of diabetes, a methylglyoxal scavenger reduced hyperalgesia.