Central modulation of spinal nociceptive synaptic transmission in vivo

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Descending noxious inhibitory system was studied with a combination of in vivo optogenetic and electrophysiological approaches. Locus coeruleus neurons in the brain stem in vivo elicited a slow inward current without eliciting a barrage of synaptic responses in response to noxious cutaneous stimulation, and showed an excitation-inhibition, biphasic firing response. A tonic activation of the locus coeruleus neurons expressing channel rhodopsin by light stimulation excited spinal GABAergic neurons to suppress noxious synaptic transmission. Alpha2 agonist, a chronically used sedative agent, at low doses also activated the descending pontospinal noradrenergic system. The present study represents a new target for the treatment of chronic pain.