Recruitment of Spinoparabrachial Neurons by Dorsal Horn Calretinin Neurons

Highlights

• Activation of CR neurons elicits mechanical allodynia and increased spontaneous pain

• CR neurons engage pain processing sites such as the parabrachial nucleus and the amygdala

• CR neurons directly engage spinoparabrachial neurons to elicit nocifensive responses

• Reduced excitatory output from CR neurons impairs sensitivity to painful stimuli

Summary

The dorsal horn of the spinal cord is the first integration site of somatosensory inputs from the periphery. In the superficial layers of the dorsal horn, nociceptive inputs are processed by a complex network of excitatory and inhibitory interneurons whose function and connectivity remain poorly understood. We examined the role of calretinin-expressing interneurons (CR neurons) in such processing and show that they receive direct inputs from nociceptive fibers and polysynaptic inputs from touch-sensitive Aβ fibers. Their activation by chemogenetic or optogenetic stimulation produces mechanical allodynia and nocifensive responses. Furthermore, they monosynaptically engage spinoparabrachial (SPb) neurons in lamina I, suggesting CR neurons modulate one of the major ascending pain pathways of the dorsal horn. In conclusion, we propose a neuronal pathway in which CR neurons are positioned at the junction between nociceptive and innocuous circuits and directly control SPb neurons in lamina I.