Quantitative sensory test correlates with neuropathy, not with pain
The mechanisms giving rise to most chronic pain conditions are still largely unknown and only for a few cases, such as gain-of-function mutations of the voltage-gated sodium channel NaV1.7, are processes well defined at a molecular level. It is therefore a straightforward approach to compare a group of patients harbouring those NaV1.7 mutations3 with patients suffering from neuropathic pain for which the underlying mechanisms are still unknown. Importantly, a control group suffering from neuropathy without pain was included to separate effects resulting from the underlying neuropathy from those leading to pain. Quantitative sensory profiles were assessed, and epidermal nerve fiber density was analysed in all patients. Rare variants of NaV1.7 were found in approximately 10% of the patients with painful diabetic neuropathy, but in none of the patients from the nonpainful neuropathy group. The functional characterization of the yet unknown variants revealed gain-of-function changes, supporting their causal role for the pain.