School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, Australia; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, United States; Department of Neurobiology, University of Pittsburgh, Pittsburgh, United States
Tyler J Browne
School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, Australia
Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan
Sally A Dickinson
School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, Australia
Jacqueline A Iredale
School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, Australia
Mark A Gradwell
School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, Australia
Phillip Jobling
School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, Australia
Robert J Callister
School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, Australia
Christopher V Dayas
School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, Australia
School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, Australia
Nociceptive information is relayed through the spinal cord dorsal horn, a critical area in sensory processing. The neuronal circuits in this region that underpin sensory perception must be clarified to better understand how dysfunction can lead to pathological pain. This study used an optogenetic approach to selectively activate spinal interneurons that express the calcium-binding protein calretinin (CR). We show that these interneurons form an interconnected network that can initiate and sustain enhanced excitatory signaling, and directly relay signals to lamina I projection neurons. Photoactivation of CR interneurons in vivo resulted in a significant nocifensive behavior that was morphine sensitive, caused a conditioned place aversion, and was enhanced by spared nerve injury. Furthermore, halorhodopsin-mediated inhibition of these interneurons elevated sensory thresholds. Our results suggest that dorsal horn circuits that involve excitatory CR neurons are important for the generation and amplification of pain and identify these interneurons as a future analgesic target.