GABA(A) and 5-HT3 receptors are involved in dorsal root reflexes: Possiblerole in periaqueductal gray descending inhibition

The dorsal root reflex (DRR) is a measure of the central excitability of pr esynaptic inhibitory circuits in the spinal cord. Activation of the periaqu eductal gray (PAG), a center for descending inhibition of spinal cord nocic eptive transmission, induces release of variety of neurotransmitters in the spinal cord, including GABA and serotonin (5-HT). GABA has been shown to b e involved in generation of DRRs. In this study, pharmacological agents tha t influence DRRs and their possible mechanisms were investigated. DRRs were recorded in anesthetized rats from filaments teased from the cut central s tump of the left L-4 or L-5 dorsal root, using a monopolar recording electr ode. Stimulating electrodes were placed either on the left sciatic nerve or transcutaneously in the left foot. Animals were paralyzed and maintained b y artificial ventilation. Drugs were applied topically to the spinal cord. A total of 64 units were recorded in 34 Sprague-Dawley rats. Peripheral rec eptive fields were found for nine of these units. In these units, DRRs were evoked by brush, pressure, and pinch stimuli. Nine units were tested for a n effect of electrical stimulation in the periaqueductal gray on the DRRs. In eight cases, DRR responses were enhanced following PAG stimulation. The background activity was 4.2 +/- 1.9 spikes/s (mean +/- SE; range: 0-97.7; n = 57). The responses to agents applied to the spinal cord were (in spikes/ s): artificial cerebrospinal fluid, 7.1 +/- 3.6 (range: 0-86.9; n = 25); 0. 1 mM GABA, 16.8 +/- 8.7 (range: 0-191.0; n = 22); 1.0 mM GABA, 116.0 +/- 26 .5 (range: 0.05-1001.2; n = 50); and 1.0 mM phenylbiguanide (PBG), 68.1 +/- 25.3 (range: 0-1,073.0; n = 49). Bicuculline (0.5 mM, n = 27) and ondanset ron (1.0 mM, n = 10) blocked the GABA and PBG effects, respectively (P< 0.0 5). Significant cross blockade was also observed. It is concluded that GABA (A) receptors are likely to play a key role in the generation of DRRs, but that 5-HT3 receptors may also contribute. DRRs can be modulated by supraspi nal mechanisms through descending systems.