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Rodolfo Delgadolezama - One of the best experts on this subject based on the ideXlab platform.
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gabaa receptors mediate motoneuron tonic inhibition in the turtle spinal cord
Neuroscience, 2011Co-Authors: Alberto Castro, Justo Aguilar, Carmen Andres, Ricardo Felix, Rodolfo DelgadolezamaAbstract:Abstract GABA A receptors mediating tonic inhibitory currents are present in neurons from hippocampus, cerebellum, sensory cortex and thalamus. These receptors located at peri- and extra-synaptic sites are constituted mainly by α 4/6 and α 5 subunits which confer them high affinity for GABA and low desensitization. Immunohistochemical and in vitro hybridization studies have shown the expression of these subunits, while functional studies have reported the presence of GABAergic tonic currents in spinal Dorsal horn neurons. However, the presence of this inhibitory current has not been documented in motoneurons. In addition, we previously reported that the monosynaptic reflex is facilitated by furosemide, an antagonist of the α 4/6 GABA A receptors, without affecting the Dorsal Root Potential, which suggests the presence of a GABAergic tonic inhibitory current in motoneurons. The aim of this work was to investigate the presence of high affinity GABA A receptors in motoneurons. By intracellular recordings made with sharp electrodes and the whole-cell patch clamp recording technique we show here that the membrane input resistance and the monosynaptic excitatory post-synaptic Potential (EPSPs) are significantly increased by bicuculline. Likewise, the depression of the EPSPs and the input membrane resistance normally induced by muscimol was partially reverted by 20 μM bicuculline and abolished when the concentration of the antagonist was raised to 100 μM. Last, bicuculline at low concentration did not affect the holding current as occur with the high concentration that block the tonic inhibitory GABAergic current. Together these results suggest that the excitability in motoneurons may be tonically inhibited by high affinity GABA A receptors.
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pre and postsynaptic modulation of monosynaptic reflex by gabaa receptors on turtle spinal cord
The Journal of Physiology, 2010Co-Authors: Wendy Bautista, Justo Aguilar, Jose Emanuel Loezaalcocer, Rodolfo DelgadolezamaAbstract:There is growing evidence that activation of high affinity extrasynaptic GABAA receptors in the brain, cerebellum and spinal cord substantia gelatinosa results in a tonic inhibition controlling postsynaptic excitability. The aim of the present study was to determine if GABAA receptors mediating tonic inhibition participate in the modulation of monosynaptic reflex (MSR) in the vertebrate spinal cord. Using an in vitro turtle lumbar spinal cord preparation, we show that conditioning stimulation of a Dorsal Root depressed the test monosynaptic reflex (MSR) at long condition–test intervals. This long duration inhibition is similar to the one seen in mammalian spinal cord and it is dependent on GABAA as it was completely blocked by 20 μm picrotoxin (PTX) or bicuculline (BIC) or 1 μm gabazine, simultaneously depressing the Dorsal Root Potential (DRP) without MSR facilitation. Interestingly 100 μm picrotoxin or BIC potentiated the MSR, depressed the DRP, and produced a long lasting motoneurone after-discharge. Furosemide, a selective antagonist of extrasynaptic GABAA receptors, affects receptor subtypes with α4/6 subunits, and in a similar way to higher concentrations of PTX or BIC, also potentiated the MSR but did not affect the DRP, suggesting the presence of α4/6 GABAA receptors at motoneurones. Our results suggest that (1) the turtle spinal cord has a GABAA mediated long duration inhibition similar to presynaptic inhibition observed in mammals, (2) GABAA receptors located at the motoneurones and primary afferents might produce tonic inhibition of monosynaptic reflex, and (3) GABAA receptors modulate motoneurone excitability reducing the probability of spurious and inappropriate activation.
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heterosynaptic modulation of the Dorsal Root Potential in the turtle spinal cord in vitro
Experimental Brain Research, 2007Co-Authors: Raul E Russo, Rodolfo Delgadolezama, Jorn HounsgaardAbstract:In the somatosensory system, the flow of sensory information is regulated at early stages by presynaptic inhibition. Recent findings have shown that the mechanisms generating the primary afferent depolarization (PAD) associated with presynaptic inhibition are complex, with some components mediated by a non-spiking mechanism. How sensory inputs carried by neighbouring afferent fibres interact to regulate the generation of PAD, and thus presynaptic inhibition, is poorly known. Here, we investigated the interaction between neighbouring primary afferents for the generation of PAD in an in vitro preparation of the turtle spinal cord. To monitor PAD we recorded the Dorsal Root Potential (DRP), while the simultaneous cord dorsum Potential (CDP) was recorded to assess the population postsynaptic response. We found that the DRP and the CDP evoked by a primary afferent test stimulus was greatly reduced by a conditioning activation of neighbouring primary afferents. This depression had early and late components, mediated in part by GABAA and GABAB receptors, since they were reduced by bicuculline and SCH 50911 respectively. However, with the selective stimulation of C and Adelta fibres in the presence of TTX, the early and late depression of the DRP was replaced by facilitation of the GABAergic and glutamatergic components of the TTX-resistant DRP. Our findings suggest a subtle lateral excitatory interaction between primary afferents for the generation of PAD mediated by a non-spiking mechanism that may contribute to shaping of information transmitted by C and Adelta fibres in a spatially confined scale in analogy with the retina and olfactory bulb.
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Dorsal Root Potential produced by a ttx insensitive micro circuitry in the turtle spinal cord
The Journal of Physiology, 2000Co-Authors: Raul E Russo, Rodolfo Delgadolezama, Jorn HounsgaardAbstract:Primary afferent fibres enter the spinal cord via Dorsal Roots and establish synaptic contacts with a wide variety of neurones. Some of these contacts occur in synaptic arrangements wherein primary afferent terminals are both pre- and postsynaptic to axon terminals and dendrites (see Willis & Coggeshall, 1991, for review). This suggests a complex regulation of information transfer at the early stages of somatosensory processing. A broad repertoire of ionotropic and metabotropic receptors in primary afferent terminals (Coggeshall & Carlton, 1997) might contribute to this regulation. Among ionotropic receptors, GABAA receptors are thought to mediate presynaptic inhibition and to be the main generators of synaptically evoked primary afferent depolarization (Rudom’n & Schmidt, 1999; Willis, 1999). Primary afferent terminals also contain ionotropic receptors for glutamate (Liu et al. 1994; Coggeshall & Carlton, 1997) but their function is not well known. In the present study, we used the Dorsal Root Potential (DRP) in a slice preparation of the turtle spinal cord to monitor the voltage response in primary afferent terminals evoked by activation of Dorsal Root fibres. We found that a component of the evoked DRP was insensitive to the blocking of GABAA receptors. Rather, it depended on the activation of AMPA and NMDA receptors. A DRP with GABA- and glutamate-mediated components was still recorded in the presence of TTX. These results suggest that interactions between primary afferent terminals can be mediated by a TTX-insensitive, probably non-spiking micro-circuit.
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rapid report Dorsal Root Potential produced by a ttx insensitive micro circuitry in the turtle spinal cord
2000Co-Authors: Raul E Russo, Rodolfo Delgadolezama, Jorn HounsgaardAbstract:1. The mechanisms underlying the Dorsal Root Potential (DRP) were studied in transverse slices of turtle spinal cord. DRPs were evoked by stimulating one filament in a Dorsal Root and were recorded from another such filament. 2. The DRP evoked at supramaximal stimulus intensity was reduced but not eliminated after blockade of GABA A receptors. The remaining component was eliminated by blocking NMDA and AMPA receptors. 3. The DRP was reduced but not eliminated after blockade of AMPA receptors. The early component of the remaining DRP was dependent on GABA A receptors and the residual component on NMDA receptors. 4. The DRP was reduced but not eliminated by TTX. GABA A , NMDA and AMPA receptors contributed to the generation of the TTX-insensitive DRP. The early component of the DRP in the presence of TTX depended on GABA A receptor activation, and the late component mainly on the activation of NMDA receptors. 5. Our results show that part of the DRP is generated by a TTX-resistant, probably non-spiking micro-circuit with separate components mediated by GABA and glutamate.
Jorn Hounsgaard - One of the best experts on this subject based on the ideXlab platform.
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heterosynaptic modulation of the Dorsal Root Potential in the turtle spinal cord in vitro
Experimental Brain Research, 2007Co-Authors: Raul E Russo, Rodolfo Delgadolezama, Jorn HounsgaardAbstract:In the somatosensory system, the flow of sensory information is regulated at early stages by presynaptic inhibition. Recent findings have shown that the mechanisms generating the primary afferent depolarization (PAD) associated with presynaptic inhibition are complex, with some components mediated by a non-spiking mechanism. How sensory inputs carried by neighbouring afferent fibres interact to regulate the generation of PAD, and thus presynaptic inhibition, is poorly known. Here, we investigated the interaction between neighbouring primary afferents for the generation of PAD in an in vitro preparation of the turtle spinal cord. To monitor PAD we recorded the Dorsal Root Potential (DRP), while the simultaneous cord dorsum Potential (CDP) was recorded to assess the population postsynaptic response. We found that the DRP and the CDP evoked by a primary afferent test stimulus was greatly reduced by a conditioning activation of neighbouring primary afferents. This depression had early and late components, mediated in part by GABAA and GABAB receptors, since they were reduced by bicuculline and SCH 50911 respectively. However, with the selective stimulation of C and Adelta fibres in the presence of TTX, the early and late depression of the DRP was replaced by facilitation of the GABAergic and glutamatergic components of the TTX-resistant DRP. Our findings suggest a subtle lateral excitatory interaction between primary afferents for the generation of PAD mediated by a non-spiking mechanism that may contribute to shaping of information transmitted by C and Adelta fibres in a spatially confined scale in analogy with the retina and olfactory bulb.
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Dorsal Root Potential produced by a ttx insensitive micro circuitry in the turtle spinal cord
The Journal of Physiology, 2000Co-Authors: Raul E Russo, Rodolfo Delgadolezama, Jorn HounsgaardAbstract:Primary afferent fibres enter the spinal cord via Dorsal Roots and establish synaptic contacts with a wide variety of neurones. Some of these contacts occur in synaptic arrangements wherein primary afferent terminals are both pre- and postsynaptic to axon terminals and dendrites (see Willis & Coggeshall, 1991, for review). This suggests a complex regulation of information transfer at the early stages of somatosensory processing. A broad repertoire of ionotropic and metabotropic receptors in primary afferent terminals (Coggeshall & Carlton, 1997) might contribute to this regulation. Among ionotropic receptors, GABAA receptors are thought to mediate presynaptic inhibition and to be the main generators of synaptically evoked primary afferent depolarization (Rudom’n & Schmidt, 1999; Willis, 1999). Primary afferent terminals also contain ionotropic receptors for glutamate (Liu et al. 1994; Coggeshall & Carlton, 1997) but their function is not well known. In the present study, we used the Dorsal Root Potential (DRP) in a slice preparation of the turtle spinal cord to monitor the voltage response in primary afferent terminals evoked by activation of Dorsal Root fibres. We found that a component of the evoked DRP was insensitive to the blocking of GABAA receptors. Rather, it depended on the activation of AMPA and NMDA receptors. A DRP with GABA- and glutamate-mediated components was still recorded in the presence of TTX. These results suggest that interactions between primary afferent terminals can be mediated by a TTX-insensitive, probably non-spiking micro-circuit.
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rapid report Dorsal Root Potential produced by a ttx insensitive micro circuitry in the turtle spinal cord
2000Co-Authors: Raul E Russo, Rodolfo Delgadolezama, Jorn HounsgaardAbstract:1. The mechanisms underlying the Dorsal Root Potential (DRP) were studied in transverse slices of turtle spinal cord. DRPs were evoked by stimulating one filament in a Dorsal Root and were recorded from another such filament. 2. The DRP evoked at supramaximal stimulus intensity was reduced but not eliminated after blockade of GABA A receptors. The remaining component was eliminated by blocking NMDA and AMPA receptors. 3. The DRP was reduced but not eliminated after blockade of AMPA receptors. The early component of the remaining DRP was dependent on GABA A receptors and the residual component on NMDA receptors. 4. The DRP was reduced but not eliminated by TTX. GABA A , NMDA and AMPA receptors contributed to the generation of the TTX-insensitive DRP. The early component of the DRP in the presence of TTX depended on GABA A receptor activation, and the late component mainly on the activation of NMDA receptors. 5. Our results show that part of the DRP is generated by a TTX-resistant, probably non-spiking micro-circuit with separate components mediated by GABA and glutamate.
Malcolm Lidierth - One of the best experts on this subject based on the ideXlab platform.
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Local and diffuse mechanisms of primary afferent depolarization and presynaptic inhibition in the rat spinal cord
The Journal of Physiology, 2006Co-Authors: Malcolm LidierthAbstract:Two types of Dorsal Root Potential (DRP) were found in the spinal cord of urethane-anaesthetized rats. Local DRPs with short latency-to-onset were evoked on Roots close to the point of entry of an afferent volley. Diffuse DRPs with a longer latency-to-onset were seen on more distant Roots up to 17 segments from the volley entry zone. The switch to long latency-to-onset occurred abruptly as a function of distance along the cord and could not be explained by conduction delays within the Dorsal columns. Long-latency DRPs were also present and superimposed on the short-latency DRPs on nearby Roots. Both local and diffuse DRPs were evoked by light mechanical stimuli: von Frey hair thresholds were ≤ 1 gram force Changes in excitability of the terminals of sural nerve afferents were used to confirm that both local and diffuse DRPs were associated with primary afferent depolarization (PAD). These effects were potent: the area of the antidromic volley evoked in the sural nerve by intraspinal microstimulation in the L4/5 spinal segment was increased by 109 ± 50% (mean ±s.d.; n= 5) by nearby conditioning stimuli, and by 52 ± 12% (n= 6) with stimuli applied 9–13 mm (5–8 segments) away. The time course of the changes in terminal excitability closely matched those of the DRPs. Reduction of the field Potentials evoked in the Dorsal horn by stimulation of Dorsal Roots was also shown to accompany both local and diffuse DRPs. The area of the monosynaptically evoked field Potential was reduced by 48 ± 19% (n= 7) with nearby conditioning stimulation and 16 ± 9% (n= 10) with stimulation 9–12 mm distant. Evidence is presented that this inhibition includes a presynaptic component. Similar effects were seen with field Potentials evoked by sural nerve stimulation. It is concluded that diffuse DRPs are mediated through propriospinal networks which may contribute to the gating of sensory information flow during natural behaviour as they respond to weak mechanical stimuli and provoke presynaptic inhibition.
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Dorsal horn cells connected to the lissauer tract and their relation to the Dorsal Root Potential in the rat
Journal of Neurophysiology, 1998Co-Authors: Malcolm Lidierth, Patrick D WallAbstract:We have examined the role of Dorsal horn cells that respond to Lissauer tract stimulation in regulating primary afferent depolarization (PAD). PAD was monitored by recording the Dorsal Root Potential (DRP) in the Roots of the lumbar cord. Recordings were made of the discharges of Lissauer tract-responsive cells, and their discharges were correlated with the DRPs occurring spontaneously and those evoked by stimulation. Electrical microstimulation of the Lissauer tract (<10 microA; 200 micros) was used to activate the tract selectively and evoke a characteristic long-latency DRP. Cells that were excited by Lissauer tract stimulation were found in the superficial laminae of the Dorsal horn. They exhibited low rates of ongoing discharge and responded to Lissauer tract stimulation typically with a burst of impulses with a latency to onset of 5.6 +/- 2.7 ms (mean +/- SD) and to termination of 13.6 +/- 4.1 ms (n = 105). Lissauer tract-responsive cells in L5 were shown to receive convergent inputs from cutaneous and muscle afferents as they responded to stimulation of the sural nerve (100%, n = 19) and the nerve to gastrocnemius (95%, n = 19). The latency of the response to sural nerve stimulation was 3.7 +/- 1.5 ms and to gastrocnemius nerve stimulation, 8.3 +/- 3.6 ms. Stimulation through a microelectrode at a depth of 1.5 mm in the sensorimotor cortex (100 microA, 200 micros) evoked a response in 17 of 31 Lissauer tract-responsive cells (55%) with a latency to onset of 21.9 +/- 2.8 ms (n = 17). Stimulation of the sural nerve, nerve to gastrocnemius or sensorimotor cortex was shown to depress the response of Lissauer tract-responsive cells to a subsequent Lissauer tract stimulus. The ongoing discharges of Lissauer tract-responsive cells were correlated to the spontaneous DRP using spike-triggered averaging. Of 123 cells analyzed in this way, 117 (95%) were shown to be correlated to the DRP. In addition, the peaks of spontaneous negative DRPs in spinally transected animals were detected in software. Perievent time histograms triggered from these peaks showed the discharge of Lissauer tract-responsive cells to be correlated to the spontaneous DRPs in 57 of 62 cells (92%) recorded. We conclude that these data provide compelling evidence that the Lissauer tract, and the Dorsal horn cells that it excites, mediate the PAD evoked from multiple neural pathways.
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five sources of a Dorsal Root Potential their interactions and origins in the superficial Dorsal horn
Journal of Neurophysiology, 1997Co-Authors: Patrick D Wall, Malcolm LidierthAbstract:Wall, Patrick D. and Malcolm Lidierth. Five sources of a Dorsal Root Potential: their interactions and origins in the superficial Dorsal horn. J. Neurophysiol. 78: 860–871, 1997. The Dorsal Root po...
Raul E Russo - One of the best experts on this subject based on the ideXlab platform.
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heterosynaptic modulation of the Dorsal Root Potential in the turtle spinal cord in vitro
Experimental Brain Research, 2007Co-Authors: Raul E Russo, Rodolfo Delgadolezama, Jorn HounsgaardAbstract:In the somatosensory system, the flow of sensory information is regulated at early stages by presynaptic inhibition. Recent findings have shown that the mechanisms generating the primary afferent depolarization (PAD) associated with presynaptic inhibition are complex, with some components mediated by a non-spiking mechanism. How sensory inputs carried by neighbouring afferent fibres interact to regulate the generation of PAD, and thus presynaptic inhibition, is poorly known. Here, we investigated the interaction between neighbouring primary afferents for the generation of PAD in an in vitro preparation of the turtle spinal cord. To monitor PAD we recorded the Dorsal Root Potential (DRP), while the simultaneous cord dorsum Potential (CDP) was recorded to assess the population postsynaptic response. We found that the DRP and the CDP evoked by a primary afferent test stimulus was greatly reduced by a conditioning activation of neighbouring primary afferents. This depression had early and late components, mediated in part by GABAA and GABAB receptors, since they were reduced by bicuculline and SCH 50911 respectively. However, with the selective stimulation of C and Adelta fibres in the presence of TTX, the early and late depression of the DRP was replaced by facilitation of the GABAergic and glutamatergic components of the TTX-resistant DRP. Our findings suggest a subtle lateral excitatory interaction between primary afferents for the generation of PAD mediated by a non-spiking mechanism that may contribute to shaping of information transmitted by C and Adelta fibres in a spatially confined scale in analogy with the retina and olfactory bulb.
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Dorsal Root Potential produced by a ttx insensitive micro circuitry in the turtle spinal cord
The Journal of Physiology, 2000Co-Authors: Raul E Russo, Rodolfo Delgadolezama, Jorn HounsgaardAbstract:Primary afferent fibres enter the spinal cord via Dorsal Roots and establish synaptic contacts with a wide variety of neurones. Some of these contacts occur in synaptic arrangements wherein primary afferent terminals are both pre- and postsynaptic to axon terminals and dendrites (see Willis & Coggeshall, 1991, for review). This suggests a complex regulation of information transfer at the early stages of somatosensory processing. A broad repertoire of ionotropic and metabotropic receptors in primary afferent terminals (Coggeshall & Carlton, 1997) might contribute to this regulation. Among ionotropic receptors, GABAA receptors are thought to mediate presynaptic inhibition and to be the main generators of synaptically evoked primary afferent depolarization (Rudom’n & Schmidt, 1999; Willis, 1999). Primary afferent terminals also contain ionotropic receptors for glutamate (Liu et al. 1994; Coggeshall & Carlton, 1997) but their function is not well known. In the present study, we used the Dorsal Root Potential (DRP) in a slice preparation of the turtle spinal cord to monitor the voltage response in primary afferent terminals evoked by activation of Dorsal Root fibres. We found that a component of the evoked DRP was insensitive to the blocking of GABAA receptors. Rather, it depended on the activation of AMPA and NMDA receptors. A DRP with GABA- and glutamate-mediated components was still recorded in the presence of TTX. These results suggest that interactions between primary afferent terminals can be mediated by a TTX-insensitive, probably non-spiking micro-circuit.
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rapid report Dorsal Root Potential produced by a ttx insensitive micro circuitry in the turtle spinal cord
2000Co-Authors: Raul E Russo, Rodolfo Delgadolezama, Jorn HounsgaardAbstract:1. The mechanisms underlying the Dorsal Root Potential (DRP) were studied in transverse slices of turtle spinal cord. DRPs were evoked by stimulating one filament in a Dorsal Root and were recorded from another such filament. 2. The DRP evoked at supramaximal stimulus intensity was reduced but not eliminated after blockade of GABA A receptors. The remaining component was eliminated by blocking NMDA and AMPA receptors. 3. The DRP was reduced but not eliminated after blockade of AMPA receptors. The early component of the remaining DRP was dependent on GABA A receptors and the residual component on NMDA receptors. 4. The DRP was reduced but not eliminated by TTX. GABA A , NMDA and AMPA receptors contributed to the generation of the TTX-insensitive DRP. The early component of the DRP in the presence of TTX depended on GABA A receptor activation, and the late component mainly on the activation of NMDA receptors. 5. Our results show that part of the DRP is generated by a TTX-resistant, probably non-spiking micro-circuit with separate components mediated by GABA and glutamate.
Joan J Kendig - One of the best experts on this subject based on the ideXlab platform.
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enflurane actions on spinal cords from mice that lack the β3 subunit of the gabaa receptor
Anesthesiology, 2001Co-Authors: Shirley M E Wong, Gong Cheng, Gregg E Homanics, Joan J KendigAbstract:BACKGROUND: Gamma-aminobutyric acid type A (GABA(A)) receptors are considered important in mediating anesthetic actions. Mice lacking the beta3 subunit of this receptor (beta3-/-) have a higher enflurane minimum alveolar concentration (MAC) than wild types (+/+). MAC is predominantly determined in spinal cord. METHODS: The authors measured three population-evoked responses in whole spinal cords, namely, the excitatory postsynaptic Potential (pEPSP), the slow ventral Root Potential (sVRP), and the Dorsal Root Potential. Synaptic and glutamate-evoked currents from motor neurons in spinal cord slices were also measured. RESULTS: Sensitivity of evoked responses to enflurane did not differ between +/+ and -/- cords. The GABA(A) receptor antagonist bicuculline significantly (P < 0.05) attenuated the depressant effects of enflurane on pEPSP, sVRP and glutamate-evoked currents in +/+ but not -/- cords. The glycine antagonist strychnine elevated the pEPSP to a significantly greater extent in -/- than in +/+ cords, but the interactions between strychnine and enflurane did not differ between -/- and +/+ cords. CONCLUSIONS: Similar enflurane sensitivity in spinal cords from -/- and +/+ mice was coupled with a decreased role for GABA(A) receptors in mediating the actions of enflurane in the former. This finding implies that other anesthetic targets substitute for GABA(A) receptors. Increase in glycine receptor-mediated inhibition was found in -/- cords, but the glycine receptor does not appear to be a substitute anesthetic target. This mutation thus led to a quantitative change in the molecular basis for anesthetic depression of spinal neurotransmission in a fashion not predicted by the mutation itself. The results argue against an immutable dominant role for GABA(A) receptors in mediating spinal contributions to MAC.
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propofol and barbiturate depression of spinal nociceptive neurotransmission
Anesthesiology, 1992Co-Authors: Brian A Jewett, Lisa M Gibbs, Ariel Tarasiuk, Joan J KendigAbstract:Barbiturates are often described as non-analgesic or even hyperalgesic agents; the newer intravenous anesthetic agent propofol is said to be non-analgesic. Both propofol and barbiturates occupy sites on the GABAA receptor. The present study was designed to compare the effects of propofol and barbiturates on nociceptive-related neurotransmission in neonatal rat spinal cord; to search for actions that might be hyperalgesic; and to determine the extent to which propofol depression of nociceptive neurotransmission is mediated by GABAA receptors. The monosynaptic reflex, a slow ventral Root Potential (slow VRP) and the Dorsal Root Potential (DRP) were recorded from isolated neonatal (1-5 days old) superfused rat spinal cords in response to electrical stimulation of a lumbar Dorsal Root. The slow VRP and the DRP are related to nociception. Propofol (0.5-10 microM), pentobarbital (1-10 microM), and thiopental (1-10 microM) reversibly depressed the slow VRP. Dose-response curves were monophasic and linear over this range. The monosynaptic reflex was unaffected. The GABAA agonist muscimol (0.2-1 microM) also depressed the slow VRP. Propofol and barbiturate slow VRP depression was antagonized by the GABAA antagonist bicuculline (1 microM). Propofol depressed the response evoked by direct application of substance P. The DRP is a GABAA-mediated depolarization of primary afferent nerve terminals that diminishes the effectiveness of nociceptive input. Propofol and thiopental increased electrically evoked DRP amplitude and increased the DRP evoked by application of muscimol. Both propofol and barbiturates thus depressed the nociceptive-related slow VRP and enhanced the antinociceptive DRP; their effective concentrations are at or close to the general anesthetic range for these agents. No anti-analgesic or hyperalgesic effect was observed. (ABSTRACT TRUNCATED AT 250 WORDS)