GABA‐receptor control of the amplitude and duration of the neuronal responses to formalin in the rat spinal cord

Abstract

The GABAergic inhibitory system in the dorsal horn of the spinal cord has been implicated in the modulation of pain, including the control of nociceptive transmission during inflammation. This electrophysiological study examined the effects of the GABAA and GABAB receptor antagonists, bicuculline and CGP35348, on the magnitude and duration of the formalin response. The responses of spinal nociceptive dorsal horn neurones to subcutaneous injection of formalin into the hindpaw in the anaesthetized rat were recorded. Both phases of the formalin response were monitored, and the antagonists were administered either simultaneously with formalin or 50 min after injection of formalin. Bicuculline (50 microg), the GABAA antagonist, administered simultaneously with formalin significantly increased the magnitude of the overall response, especially the second phase, and also abolished the silent interphase period. In addition, 50 min after injection of formalin, bicuculline increased the duration of the second phase in a dose-dependent manner. CGP35348 (250 microg), the GABAB antagonist, administered 50 min after injection of formalin also increased the duration of the second phase significantly, but had no effect on the magnitude of the response or the silent interphase when administered simultaneously with formalin. These results show that GABAA- and GABAB-receptor-mediated inhibitions are involved in controlling the duration of the second phase of the formalin response, and that GABAA-receptor-mediated inhibition also contributes to the manifestation of the silent interphase period and the magnitude of the second phase. Thus, GABA neurones are critical in determining the level and duration of nociceptive information transmitted through the spinal cord during inflammation.

Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives

“…At physiologic pH GABA is poorly permeable to the BBB but the pH of the CSF is acidic relative to the plasma, which makes GABA esters prodrugs that cross the BBB release GABA in the CNS through the action of esterases . GABA B receptors are involved in the modulation of nociception at the spinal cord and brainstem . Recently, it was demonstrated that the activation of GABA B receptors in the thalamus by baclofen, an agonist of GABA B receptor, or blockage by the antagonist CGP35348, induced an antinociceptive effect .…”

Chloride regulation in the pain pathway

“…In contrast, spontaneous nociceptive behavior is facilitated by GABA A receptor antagonists (Kaneko and Hammond, 1997) and inhibited by GABA A receptor agonists (Dirig and Yaksh, 1995; Kaneko and Hammond, 1997) in the formalin model. This behavioral profile is mirrored by changes in activity in dorsal horn neurons (Green and Dickenson, 1997). Given evidence that formalin evoked nociceptive behavior depends, at least in part, on capsaicin sensitive afferents (Peterson et al, 1997), and that afferent activity evoked during phase I of the formalin test (McCall et al, 1996) is comparable to that evoked by capsaicin (Schmelz et al, 2000), differences in GABA A receptor dependent signaling in these acute models is unlikely to depend on the initial afferent activity or which fibers are activated.…”

Administration of baclofen, a γ‐aminobutyric acid type B agonist in the thalamic ventrobasal complex, attenuates allodynia in monoarthritic rats subjected to the ankle‐bend test

“…Several studies have implicated GABA B receptors in pain‐processing mechanisms in the spinal cord (Castro‐Lopes et al, 1995; Dirig and Yaksh, 1995; Lin et al, 1996; Green and Dickenson, 1997) and brainstem (Thomas et al, 1995, 1996; Hammond et al, 1998; Pinto et al, 2003). In the thalamic VB, a decrease in GABA B 1b receptor mRNA was recently observed on the side contralateral to the arthritic joint of MA rats (Ferreira‐Gomes et al, 2004).…”