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Eur J Neurosci. 2013 Feb;37(3):417-28. doi: 10.1111/ejn.12048. Epub 2012 Nov 9.

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

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1
Clermont Université, Université d'Auvergne, Neuro-Dol, BP 10448, F-63000, Clermont-Ferrand & Inserm U1107, F-63001 Clermont-Ferrand, France.

Abstract

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 GABA(A) 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 GABA(B) 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 GABA(B) 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 GABA(B) 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.

PMID:
23136905
DOI:
10.1111/ejn.12048
[Indexed for MEDLINE]
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