Peripheral Gating of Nociception Investigated with a Decerebrate, Arterially Perfused Preparation of the Rat

Abstract

There is growing evidence that sensory neurons within the dorsal root ganglia (DRGs) are equipped with mechanisms for “gating” nociceptive information before it enters the central nervous system. However, direct in vivo evidence remains limited due to the anatomical inaccessibility of the DRG. Here, we developed a decerebrate, arterially perfused preparation of the rat (of either sex) that allows simultaneous recordings from the C8 spinal nerve (SN) and dorsal root (DR), with full access to the corresponding DRG in the absence of anesthesia. The C8 segment contributes to the median nerve supplying the forepaw, which was used for sensory stimulation. Spikes in DR were recorded and temporally matched to their origin spikes in the SN. Noxious mechanical stimulation to the forepaw increased firing in both the SN and the DR, and application of GABA (200 µM) or the GABA reuptake inhibitor, NO-711 (200 µM), directly into the DRG significantly reduced firing frequency only in the DR without affecting SN activity. Spike sorting revealed that this reduction in the spike rate from SN to DR, a phenomenon we term here as “filtering,” was greater for C-fiber spikes compared with A-fiber spikes. Innocuous stimuli (brush/cotton bud strokes and proprioceptive stimulation) also increased firing in both SN and DR, but GABA application into the DRG failed to reduce DR firing rates. Taken together, our findings lend direct support to the hypothesis of peripheral gating of the nociceptive signaling at the DRG and highlight the therapeutic potential of these peripheral structures.