Peripheral GABA(A) receptors: Evidence for peripheral primary afferent depolarization

S. M. Carlton, S. Zhou, R. E. Coggeshall

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

We propose that the primary afferent depolarization that follows GABA(A) receptor activation in the spinal cord also occurs in the periphery. As evidence, the present study localizes β2/β3 and α1 subunits of the GABA(A) receptor on 10-14% of the unmyelinated primary afferents axons in the glabrous skin of the cat paw. Behavioral studies demonstrate that local peripheral injection of the GABA(A) agonist muscimol at a low concentration (2.0μM) attenuates, and at a high concentration (1mM) enhances, formalin-induced nociceptive behaviors. Intraplantar injection of muscimol alone at a high dose evokes thermal hyperalgesia. Bicuculline, a GABA(A) antagonist, prevents these muscimol-induced changes in behavior. The muscimol-induced effects are due to local rather than systemic or central activation of GABA(A) receptors, as such effects are not observed in the contralateral paw.We interpret these findings to indicate that activation of GABA(A) receptors by low concentrations of muscimol depolarizes peripheral primary afferent terminals, a phenomenon we call peripheral primary afferent depolarization, in turn reducing the size of the peripheral action potentials and concomitantly reducing the amount of algogenic substances released from the peripheral terminals of these fibers. This sequence of events presumably results in a reduction in nociceptor activation. Higher concentrations of muscimol further depolarize GABA(A) receptor-containing terminals, which then initiates action potentials in nociceptors analogous to the appearance of dorsal root reflexes that arise following activation of GABA(A) receptors on central primary afferent terminals. These latter events reverse the analgesic effects of GABA(A) ligands and lead to potentiation of nociceptive input. Thus, the present study provides anatomical and behavioral evidence supporting a bimodal role for GABA(A) receptors in the modulation of peripheral nociceptive transmission. Copyright (C) 1999 IBRO.

Original languageEnglish (US)
Pages (from-to)713-722
Number of pages10
JournalNeuroscience
Volume93
Issue number2
DOIs
StatePublished - Jul 1999

Fingerprint

Muscimol
GABA-A Receptors
Nociceptors
Action Potentials
GABA-A Receptor Agonists
GABA-A Receptor Antagonists
Injections
Bicuculline
Spinal Nerve Roots
Hyperalgesia
gamma-Aminobutyric Acid
Formaldehyde
Axons
Reflex
Analgesics
Spinal Cord
Cats
Ligands
Skin

Keywords

  • Bicuculline
  • Muscimol
  • Nociceptors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Peripheral GABA(A) receptors : Evidence for peripheral primary afferent depolarization. / Carlton, S. M.; Zhou, S.; Coggeshall, R. E.

In: Neuroscience, Vol. 93, No. 2, 07.1999, p. 713-722.

Research output: Contribution to journalArticle

Carlton, S. M. ; Zhou, S. ; Coggeshall, R. E. / Peripheral GABA(A) receptors : Evidence for peripheral primary afferent depolarization. In: Neuroscience. 1999 ; Vol. 93, No. 2. pp. 713-722.
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