Silent cold-sensing neurons drive cold allodynia in neuropathic pain states

Published: May 3, 2020, 9 p.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.02.073999v1?rss=1 Authors: macdonald, d. I., Luiz, a. P., Millet, Q., Emery, E. C., wood, j. n. Abstract: Neuropathic pain patients often experience innocuous cooling as excruciating pain. The cell and molecular basis of this cold allodynia is little understood. We used in vivo calcium imaging of sensory ganglia to investigate the activity of peripheral cold-sensing neurons in three mouse models of neuropathic pain: oxaliplatin-induced neuropathy, partial sciatic nerve ligation and ciguatera poisoning. In control mice, cold-sensing neurons were few in number and small in size. In neuropathic animals with cold allodynia, a set of normally silent large-diameter neurons became sensitive to cooling. Many silent cold-sensing neurons expressed the nociceptor markers NaV1.8 and CGRP. Ablating these neurons diminished cold allodynia. Blocking KV1 voltage-gated potassium channels was sufficient to trigger de novo cold sensitivity in silent cold-sensing neurons. Thus silent cold-sensing neurons are unmasked in diverse neuropathic pain states and cold allodynia results from peripheral sensitization caused by altered nociceptor excitability. Copy rights belong to original authors. Visit the link for more info