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Papers of the Week

Papers: 9 Nov 2019 - 15 Nov 2019

Animal Studies

2019 Nov 12



Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn.


Smith KM, Browne TJ, Davis OC, Coyle A, Boyle KA, Watanabe M, Dickinson SA, Iredale JA, Gradwell MA, Jobling P, Callister RJ, Dayas CV, Hughes DI, Graham BA
Elife. 2019 Nov 12; 8.
PMID: 31713514.


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.