Axon terminals possessing α 2C-adrenergic receptors densely innervate neurons in the rat lateral spinal nucleus which respond to noxious stimulation

Abstract

The lateral spinal nucleus (LSN) in the rat spinal cord contains projection neurons that are densely innervated by peptidergic varicosities which probably originate from spinal interneurons. The α 2C-adrenoceptor (α 2C-AR) is present on axon terminals in this nucleus and therefore norepinephrine is likely to modulate input to LSN neurons. We investigated the involvement of LSN neurons in nociceptive transmission and their relationship with axons that possess α 2C-ARs. Double-labeling immunostaining experiments showed that α 2C-ARs are present on axon terminals of excitatory and inhibitory interneurons that frequently contain colocalised peptides. Electron microscopy revealed that α 2C-AR terminals are presynaptic to dendrites and somata of LSN neurons and predominantly form asymmetric synapses. We retrogradely labeled LSN neurons that project to the caudal ventrolateral medulla and combined this with induction of c-Fos expression by peripheral noxious thermal stimulation along with immunolabelling for the α 2C-AR and the substance P (neurokinin-1) receptor. This enabled us to identify neuronkinin-1 projection neurons in the LSN that express c-Fos and to determine if such cells receive contacts from α 2C-AR terminals. The results show that some LSN neurons are activated by noxious stimulation and that this input is likely to be modulated by norepinephrine acting on α 2C-ARs which are present on axon terminals that are presynaptic to LSN neurons.