C-nociceptors sensitized to cold in a patient with small-fiber neuropathy and cold allodynia

Cold allodynia is a common sign of neuropathic pain patients but its underlying mechanisms are still largely unknown, partly because the populations of neurons responding to cold stimuli and their transduction mechanisms have not been fully determined. We report a patient with a small-fiber neuropathy of unknown origin, whose main complaint is cold allodynia. Microneurographic recordings showed ongoing spontaneous activity and abnormal responses to cold and menthol in identified subtypes of C-nociceptors. These findings provide the first direct evidence in human of abnormal peripheral nociceptor behavior potentially responsible for cold allodynia. The responsiveness of C-nociceptors to menthol suggests an abnormal expression or function of TRPM8 channels in this patient with a small-fiber polyneuropathy.