Segmental disinhibition suppresses C-fiber inputs to the rat superficial medullary dorsal horn via the activation of GABAB receptors

• Published in: The European journal of neuroscience Vol. 37; no. 3; pp. 417 - 428
• Main Authors: Melin, Céline, Jacquot, Florian, Dallel, Radhouane, Artola, Alain
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01-02-2013; Blackwell
• Subjects: Action Potentials - drug effects; Animals; Baclofen - analogs & derivatives; Baclofen - pharmacology; Biological and medical sciences; Central nervous system; chronic pain; dorsal horn; Electrophysiology; Fundamental and applied biological sciences. Psychology; GABA-B Receptor Agonists - pharmacology; GABA-B Receptor Antagonists - pharmacology; GABAA receptors; glycine receptors; Male; Morphine - pharmacology; Nerve Fibers, Myelinated - physiology; Nerve Fibers, Unmyelinated - physiology; Posterior Horn Cells - metabolism; Posterior Horn Cells - physiology; Rats; Rats, Inbred Strains; Receptors, GABA-B - metabolism; Receptors, Glycine - antagonists & inhibitors; Receptors, Glycine - metabolism; sensory processing; synaptic inhibition; Synaptic Transmission - drug effects; trigeminal nerve; Vertebrates: nervous system and sense organs; Spinal cord; chronic pain; glycine receptors; Rat; receptors; dorsal horn; Rodentia; Central nervous system; synaptic inhibition; Electrophysiology; Posterior spinal horn; Nerve fiber C; Vertebrata; Chronic; sensory processing; Mammalia; Pain; Trigeminal nerve; Animal; Glycine receptor; GABA; Gabaergic receptor B; Gabaergic receptor A
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.12048

Specialized primary afferents, although they terminate in different laminae within the dorsal horn (DH), are known to interact through local circuit excitatory and inhibitory neurons. That a loss of segmental inhibition probably contributes to persistent pain hypersensitivity during chronic pain raises the question as to how disinhibition‐induced changes in cross‐modal interactions account for chronic pain symptoms. We sought to characterize how pharmacological blockade of glycine and gamma‐aminobutyric acid (GABA) receptors modifies synaptic transmission between primary afferent fibers and second‐order neurons by recording field potentials in the superficial medullary dorsal horn (MDH) of anesthetized rats. Transcutaneous electrical stimulation evokes three negative field potentials elicited by, from earliest to latest, Aβ‐, Aδ‐ and C‐fiber primary afferents. Blocking segmental glycine and/or GABAA receptors, with strychnine and bicuculline, respectively, strongly facilitates Aβ‐ and Aδ‐fiber‐evoked polysynaptic field potentials but, conversely, inhibits, or even abolishes, the whole C‐fiber field potential. Blocking segmental GABAB receptors, with phaclofen, reverses such suppression of C‐fiber field potentials. Interestingly, it also potentiates C‐fiber field potentials under control conditions. Finally, activation of segmental GABAB receptors, with baclofen, preferentially inhibits C‐fiber field potentials. Our results suggest that activation of A‐fiber primary afferents inhibits C‐fiber inputs to the MDH by the way of polysynaptic excitatory pathways, last‐order GABAergic interneurons and presynaptic GABAB receptors on C‐fiber primary afferents. Under physiological conditions, activation of such local DH circuits is closely controlled by segmental inhibition but it might contribute to paradoxically reduced pain hypersensitivity under pathological disinhibition.
Blocking glycine and/or GABA(A) receptors in the medullary dorsal horn (MDH) strongly facilitates Aβ‐ and Aδ‐fiber‐evoked polysynaptic field potentials but, conversely, inhibits C‐fiber ones. Suppression of C‐fiber field potentials is prevented by blocking segmental GABA(B) receptors. Activation of A‐fiber primary afferents might thus inhibit C‐fiber inputs to the MDH through polysynaptic excitatory pathways, last‐order GABAergic interneurons and presynaptic GABA(B) receptors on C‐fiber terminals.