RT Journal Article
SR Electronic
T1 Pregabalin Silences Oxaliplatin-Activated Sensory Neurons to Relieve Cold Allodynia
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0395-22.2022
DO 10.1523/ENEURO.0395-22.2022
VO 10
IS 2
A1 Iseppon, Federico
A1 Luiz, Ana P.
A1 Linley, John E.
A1 Wood, John N.
YR 2023
UL http://www.eneuro.org/content/10/2/ENEURO.0395-22.2022.abstract
AB Oxaliplatin is a platinum-based chemotherapeutic agent that causes cold and mechanical allodynia in up to 90% of patients. Silent Nav1.8-positive nociceptive cold sensors have been shown to be unmasked by oxaliplatin, and this event has been causally linked to the development of cold allodynia. We examined the effects of pregabalin on oxaliplatin-evoked unmasking of cold sensitive neurons using mice expressing GCaMP-3 in all sensory neurons. Intravenous injection of pregabalin significantly ameliorates cold allodynia, while decreasing the number of cold sensitive neurons by altering their excitability and temperature thresholds. The silenced neurons are predominantly medium/large mechano-cold sensitive neurons, corresponding to the “silent” cold sensors activated during neuropathy. Deletion of α2δ1 subunits abolished the effects of pregabalin on both cold allodynia and the silencing of sensory neurons. Thus, these results define a novel, peripheral inhibitory effect of pregabalin on the excitability of “silent” cold-sensing neurons in a model of oxaliplatin-dependent cold allodynia.