Activation of α-adrenoceptors depresses synaptic transmission of myelinated afferents and inhibits pathways mediating primary afferent depolarization (PAD) in the in vitro mouse spinal cord

• Published in: Experimental brain research Vol. 238; no. 5; pp. 1293 - 1303
• Main Authors: Mena-Avila, Elvia, Milla-Cruz, Jonathan J., Calvo, Jorge R., Hochman, Shawn, Villalón, Carlos M., Arias-Montaño, José-Antonio, Quevedo, Jorge N.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2020; Springer Nature B.V
• Subjects: Adrenergic alpha-Agonists - pharmacology; Adrenergic receptors; Agonists; Animals; Animals, Newborn; Biomedical and Life Sciences; Biomedicine; Clonidine; Depolarization; Dorsal horn; Dorsal roots; Electrophysiological Phenomena - drug effects; Electrophysiological Phenomena - physiology; In Vitro Techniques; Mice; Mice, Inbred BALB C; Neonates; Nerve Fibers, Myelinated - physiology; Neural Pathways - physiology; Neurology; Neurons, Afferent - physiology; Neurosciences; Neurotransmitter release; Norepinephrine; Phenylephrine; Receptors, Adrenergic, alpha-1 - drug effects; Receptors, Adrenergic, alpha-1 - physiology; Receptors, Adrenergic, alpha-2 - drug effects; Receptors, Adrenergic, alpha-2 - physiology; Research Article; Sensory neurons; Spinal cord; Spinal Cord Dorsal Horn - physiology; Synaptic transmission; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Primary afferent depolarization; Presynaptic inhibition; Spinal cord; Noradrenaline; Neuromodulation
• ISSN: 0014-4819; 1432-1106
• DOI: 10.1007/s00221-020-05805-y

Somatosensory afferent transmission strength is controlled by several presynaptic mechanisms that reduce transmitter release at the spinal cord level. We focused this investigation on the role of α-adrenoceptors in modulating sensory transmission in low-threshold myelinated afferents and in pathways mediating primary afferent depolarization (PAD) of neonatal mouse spinal cord. We hypothesized that the activation of α-adrenoceptors depresses low threshold-evoked synaptic transmission and inhibits pathways mediating PAD. Extracellular field potentials (EFPs) recorded in the deep dorsal horn assessed adrenergic modulation of population monosynaptic transmission, while dorsal root potentials (DRPs) recorded at root entry zone assessed adrenergic modulation of PAD. We found that noradrenaline (NA) and the α 1 -adrenoceptor agonists phenylephrine and cirazoline depressed synaptic transmission (by 15, 14 and 22%, respectively). DRPs were also depressed by NA, phenylephrine and cirazoline (by 62, 30, and 64%, respectively), and by the α 2 -adrenoceptor agonist clonidine, although to a lower extent (20%). We conclude that NA depresses monosynaptic transmission of myelinated afferents onto deep dorsal horn neurons via α 1 -adrenoceptors and inhibits interneuronal pathways mediating PAD through the activation of α 1 - and α 2 -adrenoceptors. The functional significance of these modulatory actions in shaping cutaneous and muscle sensory information during motor behaviors requires further study.