Ventricular excitation maps using tissue Doppler acceleration imaging: potential clinical application.

OBJECTIVES: The purpose of this study is to validate the use of tissue Doppler acceleration imaging (TDAI) for evaluation of the onset of ventricular contraction in humans. BACKGROUND: Tissue Doppler acceleration imaging can display the distribution, direction and value of ventricular acceleration responses to myocardial contraction and electrical excitation. METHODS: Twenty normal volunteers underwent TDAI testing to determine the normal onset of ventricular acceleration. Two patients with paroxysmal supraventricular tachycardia and 30 patients with permanent pacemakers underwent introduction of esophageal and right ventricular pacing electrodes, respectively, and were studied to visualize the onset of pacer-induced ventricular acceleration. Eight patients with dual atrioventricular (AV) node and 20 patients with Wolff-Parkinson-White (WPW) syndrome underwent TDAI testing to localize the abnormal onset of ventricular acceleration, and the results were compared with those of intracardiac electrophysiology (ICEP) tests. RESULTS: The normal onset and the onset of dual AV node were localized at the upper interventricular septum (IVS) under the right coronary cusp within 25 ms before the beginning of the R wave in the electrocardiogram (ECG). In all patients in the pacing group, the location and timing of the onset conformed to the positions and timing of electrodes (100%). In patients with WPW syndrome, abnormal onset was localized to portions of the ventricular wall other than the upper IVS at the delta wave or within 25 ms after the delta wave in the ECG. The agreement was 90% (18 of 20) between the abnormal onset and the position of the accessory pathways determined by ICEP testing. CONCLUSIONS: These results suggest that TDAI is a useful noninvasive method that frequently is successful in visualizing the intramural site of origin of ventricular mechanical contraction.

Temporal profile of the directional tuning of the discharge of dorsal premotor cortical cells.

This study examined the directional modulation of dorsal premotor (PMd) cells as a function of time in an instructed delay, reaching task that systematically varied direction and accuracy constraints. In two monkeys, the activity of 150 PMd cells was recorded and the preferred direction (PD) of the firing as a function of time, the PD trajectory, was calculated. Forty-one cells had nearly continuous significant directional tuning of at least 1 s duration (mean duration 1694 +/- 754 ms) that began in the instructed delay period and continued into the movement period. The PD gradually changed in time (mean change of 47.7 +/- 40.8 degrees), a change best described as a rotation. The change in the directional tuning as a function of time is consistent with the hypothesis that the PMd plays a role in the non-standard mapping of sensory stimuli into motor commands.

Relationship of cerebellar Purkinje cell simple spike discharge to movement kinematics in the monkey.

The simple spike discharge of 231 cerebellar Purkinje cells in ipsilateral lobules V and VI was recorded in three monkeys trained to perform a visually guided reaching task requiring movements of different directions and distances. The discharge of 179 cells was significantly modulated during movement to one or more targets. Mean simple spike rate was fitted to a cosine function for direction tuning, a simple linear function for distance modulation, and a multiple linear regression model that included terms for direction, distance, and target position. On the basis of the fit to the direction and distance models, there were more distance-related than direction-related Purkinje cells. The simple spike discharge of most direction-related cells modulated at only one target distance. The preferred directions for the simple spike tuning were not uniformly distributed across the workspace. The discharge of most distance-related cells modulated along only one movement direction. On the basis of the multiple linear regression model, simple spike discharge was also correlated with target position, in addition to direction and distance. Approximately half of the Purkinje cells had simple spike activity associated with only a single parameter, and only a small fraction of the cells with all three. The multiple regression model was extended to evaluate the correlations as a function of time. Considerable overlap occurred in the timing of the simple spike correlations with the parameters. The latency for correlation with movement direction occurred mainly in a 500-ms interval centered on movement onset. The correlations with target position also occurred around movement onset, in the range of -200-500 ms. Distance correlations were more variable, with onset latencies from -500 to 1,000 ms. These results demonstrate that the simple spike discharge of cerebellar Purkinje cells is correlated with movement direction, distance, and target position. Comparing these results to motor cortical discharge shows that the correlations with these parameters were weaker in Purkinje cell simple spike discharge, and that, for the majority of Purkinje cells, the simple spike discharge was significantly related to only a single movement parameter. Other differences between simple spike responses and those of motor cortical cells include the nonuniform distribution of preferred directions and the extensive overlap in the timing of the correlations. These differences suggest that Purkinje cells process, encode, and use kinematic information differently than motor cortical neurons.

Movement kinematics encoded in complex spike discharge of primate cerebellar Purkinje cells.

Monkeys performed a multijoint arm-reaching task that systematically varied movement direction and distance. Purkinje cell activity was recorded from 231 task-related cells, and the complex spike discharge was analyzed in relation to distance and direction. The complex spike activity of 123 Purkinje cells changed significantly relative to the background rate. Of these 123, the activity of 85 cells was related to distance and/or direction. The complex spike activity of 54 of these 85 cells fitted a cosine tuning curve for direction, generally at one distance. Using a simple linear regression model, the complex spike activity of 56 cells was significantly correlated with movement distance, usually in one direction. We conclude that the complex spike discharge of Purkinje cells is spatially tuned and strongly related to movement kinematics.

Inhibition of spinal nociceptive neurons by microinjections of somatostatin into the nucleus raphe magnus and the midbrain periaqueductal gray of the anesthetized cat.

The effects of somatostatin (SOM) after intravenous application and intracerebral microinjection into the medullary nucleus raphe magnus (NRM) or into the periaqueductal gray (PAG) on the spinal nociceptive transmission was quantitatively studied in the anesthetized cat. Noxious heat-evoked responses of multireceptive lumbar spinal dorsal horn neurons were reversibly depressed to 56.6 +/- 9.7% of the control after systemically applied SOM (7 micrograms/kg i.v.; 7 micrograms/kg per h infusion rate). At 11 of 14 brainstem microinjection sites in the NRM and PAG, SOM (2.5 micrograms/microliter) attenuated the heat-evoked responses to 58.9 +/- 6.2% (n = 5) (NRM) and 64.4 +/- 6.3% (n = 6) (PAG) of the control. After microinjection, maximal inhibition was reached within 8-14 min (NRM) or 23-29 min (PAG), respectively. Inhibition was reversible within 60 min after the injection. Thus, SOM has an antinociceptive potency by activating descending inhibition of nociceptive dorsal horn neurons from the NRM and PAG.

Temporal encoding of movement kinematics in the discharge of primate primary motor and premotor neurons.

1. Several neurophysiological studies of the primary motor and premotor cortices have shown that the movement parameters direction, distance, and target position are correlated with the discharge of single neurons. Here we investigate whether the correlations with these parameters occur simultaneously (i.e., parallel processing), or sequentially (i.e., serial processing). 2. The single-unit data used for the analyses presented in this paper are the same as those used in our earlier study of neuronal specification of movement parameters. We recorded the activity of single neurons in the primary motor and premotor cortices of two rhesus monkeys (Macaca mulatta) while the animals performed reaching movements made in a horizontal plane. Specifically, the animals moved from a centrally located start position to 1 of 48 targets (1 cm2) placed at eight different directions (0-360 degrees in 45 degrees intervals) and six distances (1.4-5.4 cm in 0.8-cm increments) from the start position. 3. We analyzed 130 task-related cells; of these, 127 (99 in primary motor cortex, 28 near the superior precentral sulcus) had average discharges that were significantly modulated with the movement and were related to movement direction, distance, or target position. To determine the temporal profile of the correlation of each cell's discharge with the three parameters, we performed a regression analysis of the neural discharge. We calculated partial R2s for each parameter and the total R2 for the model as a function of time. 4. The discharge of the majority of units (73.2%) was significantly correlated for some time with all three parameters. Other units were found that correlated with different combinations of pairs of parameters (21.3%), and a small number of units appeared to code for only one parameter (5.5%). There was no obvious difference in the presence of correlations between cells recorded in the primary motor versus premotor cortices. 5. On average we found a clear temporal segregation and ordering in the onset of the parameter-related partial R2 values: direction-related discharge occurred first (115 ms before movement onset), followed sequentially by target position (57 ms after movement onset) and movement distance (248 ms after movement onset). Some overlap in the timing of the correlation of these parameters was evident. We found a similar sequential ordering for the latency of the peak of the R2 curves (48, 254, and 515 ms after movement onset, respectively, for direction, target position, and distance).(ABSTRACT TRUNCATED AT 400 WORDS)

Differential effects of spinalization on discharge patterns and discharge rates of simultaneously recorded nociceptive and non-nociceptive spinal dorsal horn neurons.

Recordings were made simultaneously from 2-5 neurons at the same site in the lumbar spinal dorsal horn of pentobarbital-anesthetized rats. Neurons were classified as low-threshold (LT) or multireceptive (MR) according to their responses to non-noxious mechanical or noxious radiant heat stimuli of the skin. At the same recording sites neurons could be encountered which belong to different classes and/or which had mechanoreceptive fields which did not overlap. Cold blocks of the upper or lower thoracic cord or transsections of the upper cervical cord were made to evaluate the effects of spinalization on both the rate and pattern of background activity and/or noxious heat-evoked responses of different dorsal horn neurons under identical experimental conditions. At 24 of 27 recording sites, spinalization had qualitatively or quantitatively different effects on the rate of background activity of simultaneously recorded neurons. Interspike interval (ISI) means of background activity were significantly reduced in 29 of 65 (44.6%) neurons, prolonged in 23 of 65 (35.4%) neurons, or unchanged in 13 of 65 (20%) neurons. MR neurons displayed a significantly higher incidence of decreased background activity 17 of 45 (37.8%) and a lower incidence of increased background activity (18 of 45, 40%) during spinalization than the LT neurons from which 1 of 12 (8.3%) decreased and 8 of 12 (66.6%) increased background activity. Almost all (95.4%) neurons changed their discharge patterns after spinalization. At 9 of 27 recording sites, the discharge patterns of simultaneously recorded neurons were affected differently by spinalization as revealed by the coefficient of dispersion of the interspike intervals (ISI), indicating changes in the tendency to discharge action potential in clusters (bursts). At the same recording sites the level of noxious heat-evoked responses of simultaneously recorded MR neurons was also differentially affected by spinalization. Nociceptive responses were significantly enhanced in 19 of 37 (51.4%) neurons (137.8 +/- 142.6% of control, mean +/- SD), reduced in 13 of 37 neurons (35.1%) (by 58.9 +/- 20.9%) and/or unchanged in 5 of 37 (13.5%) neurons. It is concluded that no general 'tone' of descending antinociception exists and that tonic descending excitatory and inhibitory systems may be active simultaneously modulating both the level and pattern of neuronal discharges.

Spatial patterns of functional activation of the cerebellum investigated using high field (4 T) MRI.

Using single and multislice functional MRI at high field strength (4 T) we studied cerebellar activation in 12 subjects making a series of alternating wrist flexion and extension movements against constant inertial loads. Three spatial patterns of activation were observed: (i) parasagittal bands of activity localized primarily in the ipsilateral intermediate and lateral zones of the cerebellar hemispheres, (ii) medio-lateral bands which in some subjects followed the contour of individual folia and (iii) fragmented regions of activation covering extensive areas of the cerebellum. Bilateral activation of the cerebellum was observed in all subjects with measurable activity. Mean statistically significant activation intensity ranged from 2.34 to 13.54% above baseline.

Neuronal specification of direction and distance during reaching movements in the superior precentral premotor area and primary motor cortex of monkeys.

1. Single-unit neuronal activity was recorded in the primary motor and superior precentral premotor areas of two rhesus monkeys during an arm reaching task. The task involved moving a cursor displayed on a video terminal using a draftsman's arm-type manipulandum. From a centrally located start box the animal was required to move to 1 of 48 target boxes at eight different directions (0-360 degrees in 45 degrees intervals) and six distances (1.4-5.4 cm in 0.8-cm increments). Both direction and distance for the upcoming movement were unpredictable. 2. The activity of 197 arm movement-related cells was recorded and evaluated for each of the 48 targets. Histological examination showed the cells to be primarily in the primary motor cortex or in the premotor area around the superior precentral sulcus. Each cell's discharge was aligned on movement onset and averaged over five trials for each target. Movement kinematics including hand path velocity were also determined. The task time was divided into three epochs, a premovement period (PT), a movement period (MT), and total time (TT = PT+MT). For each epoch the average firing was correlated with the direction and distance of the movement using various regression procedures. 3. An analysis of variance (ANOVA) showed that the majority of neurons were modulated significantly by movement direction in each of the three time periods, PT (73.7%), MT (68.3%), and TT (78.5%). The relationship of the firing to direction was fit to a cosine tuning function for each significantly modulated cell. In 86.3% of the cells the firing was correlated significantly with a cosine function of movement direction in TT. A cell's preferred direction varied little for different movement distances. The mean difference in preferred direction for the smallest possible change in distance (0.8 cm) was 12.8 +/- 11.4 degrees (SD) and 17.1 +/- 14.7 degrees for the largest change in distance (4.0 cm). 4. Correlation analysis revealed that the activity of the majority of cells was modulated significantly by distance along at least one direction in each of the three time periods, PT (46.8%), MT (68.8%), and TT (67.7%). Subsequently, a univariate linear regression model was used to quantify a cell's discharge as a function of distance. For the regressions of firing with distance with a statistically significant correlation (r > 0.8), the mean slope was 3.59 +/- 0.17 spikes.s-1.cm-1 for the total time. The existence of a significant distance modulation was not invariably correlated with a cell's preferred movement direction.(ABSTRACT TRUNCATED AT 400 WORDS)

Characteristics of propriospinal modulation of nociceptive lumbar spinal dorsal horn neurons in the cat.

The segmental and laminar origin of propriospinal antinociceptive systems in the cat spinal cord and the modes to activate them are characterized. The experiments were performed on pentobarbital-anesthetized cats with a high cervical spinalization. Recordings were made from single lumbar spinal dorsal horn neurons responding to noxious radiant skin heating and to innocuous mechanical skin stimuli. The segmental and laminar origin of heterosegmental, propriospinal neurons modulating background activity and nociceptive responses were identified and the conditions to activate them were characterized. Conditioning noxious front paw stimulation and superfusion of the cervical enlargement with L-glutamate, but not with substance P, reduced noxious heat-evoked responses of about 50% of all lumbar neurons tested. Glutamate superfusions of the lower thoracic or upper sacral spinal cord enhanced background activity and reduced nociceptive responses of most lumbar spinal dorsal horn neurons. Superfusions with substance P or somatostatin were ineffective. Glutamate microinjections into the superficial layers of the thoracic, upper lumbar or sacral dorsal horn ipsi- or contralateral to the recording sites or into lamina VIII of the ipsilateral thoracic or upper lumbar cord reduced noxious heat-evoked responses with or without changes in the level of background activity. It is concluded that propriospinal neurons originating from circumscribed areas of the cervical, thoracic, lumbar or sacral spinal cord independently modulate background activity and noxious heat-evoked responses of multireceptive lumbar spinal dorsal horn neurons. The incidence and efficacy of propriospinal antinociceptive stimulation sites was found to be as high as for the classical region of endogenous antinociception, the midbrain periaqueductal gray.

Distance- and error-related discharge of cells in premotor cortex of rhesus monkeys.

Previous work on the premotor cortex has emphasized its role in preparation for movement. In this study, we concentrated on the activity that occurs during a movement, particularly when the required movement amplitude is unexpectedly changed by introduction of a visuo-spatial error. In two rhesus monkeys, discharge of premotor neurons was recorded during a multi-joint reaching movement. Units could be divided into two categories: (1) those whose discharge monotonically increased or decreased with movement amplitude; and (2) those whose discharge was modulated with the unexpected change in amplitude but not monotonically. We suggest that the latter class of cells may be detecting or responding to a visuo-motor error. Thus, the premotor cortex is not only involved in preparation but plays a role in the ongoing control of movement execution.

Evidence that C1 and C2 propriospinal neurons mediate the inhibitory effects of viscerosomatic spinal afferent input on primate spinothalamic tract neurons.

1. Lumbosacral spinothalamic tract (STT) neurons can be inhibited by noxious pinch of the contralateral hindlimb or either forelimb and by electrical stimulation of cardiopulmonary sympathetic, splanchnic, and hypogastric afferents. A previous study found that spinal transections between C2 and C4 sometimes abolished the inhibitory effect of spinal afferent input and sometimes left it intact. This suggested that propriospinal neurons in the C1 and C2 segments might mediate this effect. To test whether neurons in the C1 and C2 segments were involved in producing this inhibitory effect, the magnitude of the reduction in neural activity was measured in the same STT neuron before and after spinal transection at C1 or between C3 and C7. 2. All neurons were antidromically activated from the contralateral thalamus and thoracic spinal cord. For us to accept a neuron for analysis, the characteristics of the somatic input and the latency and shape of the antidromatic spike produced by spinal cord stimulation had to be the same before and after the spinal transection. Also, spinal transection often causes a marked increase in spontaneous cell activity, which may affect the magnitude of an inhibitory response. To avoid this confounding problem, a cell was accepted for analysis only if it showed marked inhibition of high cell activity evoked by somatic pinch before spinal transection. For analysis 13 STT neurons met these criteria: 6 neurons were in monkeys with C1 transections, and 7 neurons were in animals with transections between C3 and C7.(ABSTRACT TRUNCATED AT 250 WORDS)

Responses of neurons in ventroposterolateral nucleus of primate thalamus to urinary bladder distension.

The purpose of this study was to examine effects of a noxious visceral stimulus, urinary bladder distension (UBD), on cells in the ventroposterolateral (VPL) nucleus of anesthetized monkeys. We hypothesized that processing of visceral information in the VPL nucleus of the thalamus is similar to spinothalamic tract (STT) organization of visceral afferent input. Urinary bladder distension excites sacral and upper-lumbar STT cells that have somatic input from proximal somatic fields; whereas, thoracic STT cells are inhibited by UBD. Extracellular action potentials of 67 neurons were recorded in VPL nucleus. Urinary bladder distension excited 22 cells, inhibited 9 cells, and did not affect activity of 36 cells. Seventeen of 22 cells excited by UBD also received convergent somatic input from noxious squeeze of the hip, groin, or perineal regions. No cells activated only by innocuous somatic stimuli were excited by UBD. Five of 9 cells inhibited by UBD had upper-body somatic fields. There was a significant tendency for VPL neurons excited by UBD to have proximal lower-body somatic fields that were excited by noxious stimulation of skin and underlying muscle (P less than 0.001). Antidromic activation of 4 thalamic neurons affected by UBD showed that visceral input stimulated by UBD reached the primary somatosensory (SI) cortex.

Projection of nodose ganglion cells to the upper cervical spinal cord in the rat.

Afferent fibers mediating pain from myocardial ischemia classically are believed to travel in sympathetic nerves to enter the thoracic spinal cord. After sympathectomies, angina pectoris still may radiate to the neck and inferior jaw. Sensory fibers from those regions are thought to enter the central nervous system through upper spinal cord segments. We postulated that axons from nodose ganglion cells might project to cervical cord segments. The purpose of this study was to determine the density and pathway of vagal afferent innervation to the upper cervical spinal cord. Following an injection of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the upper cervical spinal cord, approximately 5.8% of cells in the nodose ganglion contained reaction product. Cervical vagotomy did not diminish the density of WGA-HRP labeled cells in the nodose ganglion. However, a spinal cord hemisection cranial to the injection site eliminated labeling of nodose cells. These data indicate that a portion of vagal afferent neurons project from the nodose ganglion to the upper cervical spinal cord. In addition, vagal afferent fibers reach the spinal cord via a central route rather than through dorsal root ganglia.

Characteristics of midbrain control of spinal nociceptive neurons and nonsomatosensory parameters in the pentobarbital-anesthetized rat.

1. GABAergic mechanisms in the midbrain periaqueductal gray (PAG) have been proposed to control the activity of descending antinociceptive systems and defensive behavior. Here, the effect of neuronal disinhibition by gamma-aminobutyric acid (GABAA) receptor blockade at midbrain sites on spinal neuronal responses to noxious and innocuous skin stimulation was quantitatively characterized. It was compared with the effect of direct neuronal excitation by glutamate microinjections or electrical stimulation at identical sites. Changes in mean arterial blood pressure and other nonsomatosensory responses were also assessed. 2. Responses of 101 multireceptive lumbar spinal dorsal horn neurons to noxious radiant skin heating (50 degrees C, 10 s), innocuous skin brushing, and electrical stimulation of primary afferent A- and C-fibers were recorded in deeply pentobarbital-anesthetized rats. The mean blood pressure was continuously monitored in one carotid artery, and other nonsomatosensory parameters, such as frequency and depth of spontaneous respiration and contractions of abdominal and facial muscles, were classified according to their relative intensity into five groups. 3. A fine, multibarrel glass pipette was constructed for monopolar electrical stimulation and microinjection of the GABAA receptor antagonist bicuculline (40, 200, or 400 pmol), or glutamate (10-50 nmol), or Fast Green dye in 50 or 100 nl at identical sites in the midbrain. 4. Bicuculline microinjections into discrete regions of the PAG selectively abolished spinal neuronal responses to noxious skin stimulation but did not affect brush-evoked responses or responses to electrical A-fiber stimuli. This antinociception was often, albeit not necessarily, accompanied by tachypnoea and abdominal and facial muscle contractions and changes--mostly increases--in mean arterial blood pressure. Injections into other areas of the PAG and adjoining ventral tegmentum (VT) were less effective. The vast majority of injection sites in the lateral tegmentum (LT) were ineffective. 5. Glutamate microinjections at midbrain sites to detect areas of origin of descending antinociceptive neurons were characterized by a high incidence (greater than 50%) of false-negative results, as bicuculline was shown to be effective at numerous glutamate-insensitive sites. Glutamate microinjections into some sites of the PAG and adjoining VT reduced, but did not abolish, spinal neuronal responses to noxious skin heating. Injections into the LT were ineffective. 6. The efficacy of electrical stimulation at midbrain sites on spinal nociceptive responses had no predictive value for the effect of glutamate or bicuculline.(ABSTRACT TRUNCATED AT 400 WORDS)

Spinal somatostatin superfusion in vivo affects activity of cat nociceptive dorsal horn neurons: comparison with spinal morphine.

A controversy exists concerning the role of the neuropeptide somatostatin for the transmission or inhibition of nociceptive information in the spinal cord. To better correlate electrophysiological effects of somatostatin at single cell level with results obtained with intrathecal injections of somatostatin in behaving animals and human pain patients we applied somatostatin to the spinal cord by controlled superfusion of the recording segment in vivo. The hypothesis of an opioid link and possible neurotoxic effects of somatostatin were also addressed. In cats deeply anaesthetized with pentobarbitone, halothane and nitrous oxide, extracellular recordings were made from 27 neurons located in laminae I-VI. All neurons responded to both innocuous mechanical and noxious radiant heat stimuli applied to the glabrous skin of the ipsilateral hindpaw. The dorsal surface of the spinal cord was superfused at the recording segment by means of a Perspex chamber (7 x 7 mm). Somatostatin superfusions at 1.2 microM had no effect on responses to noxious heat. Responses were, however, depressed by somatostatin at 61 microM to 59.7 +/- 5.1% of control and by somatostatin at 1.53 mM to 39.9 +/- 9.5% of control. This inhibition was not antagonized by the mu-opiate antagonist naloxone applied to the spinal cord at concentrations of 2.7 mM, either together with somatostatin, or after the inhibition by somatostatin had fully developed. Neuronal responses were linear functions of the skin temperatures for stimulation intensities between 42 degrees C and 52 degrees C. The slopes of these stimulus response functions were reduced during somatostatin superfusion at 61 microM to 46.8 +/- 9.3% of control, without changing the temperature thresholds for responding (42.5 +/- 0.6 degrees C). Somatostatin superfusion at 61 microM had no effect on the number of action potentials evoked by innocuous skin brushing, or by electrical stimulation of primary afferent A-fibres in cutaneous nerves. The amplitude of intraspinally recorded field potentials evoked by these electrical nerve stimuli was also unaffected by somatostatin. The inhibition of nociceptive spinal dorsal horn neurons by spinally administered morphine was assessed in eight experiments. Morphine reduced noxious heat-evoked responses to 42.1 +/- 9.6% of control at 0.3 mM and to 51.8 +/- 6.9% of control at 3.0 mM. The slopes of the stimulus-response functions were reduced by morphine at 0.3 mM to 53.1 +/- 11.3% of control, without changing the temperature thresholds (42.7 degrees C). Naloxone superfusion (2.7 mM) reliably antagonized the inhibition by morphine. Brush-evoked responses were not, or much less, affected by spinal morphine.(ABSTRACT TRUNCATED AT 400 WORDS)

B-vitamins enhance afferent inhibitory controls of nociceptive neurons in the rat spinal cord.

Afferent inhibition of spinal dorsal horn neuronal responses to noxious skin heating was induced by transcutaneous electrical nerve stimulation in pentobarbital-anesthetized rats. Pretreatment with B vitamins significantly enhanced this afferent inhibition, possibly due to an increase in the synthesis rate of inhibitory neurotransmitters in central neurones.

Blockade of GABAA receptors in the midbrain periaqueductal gray abolishes nociceptive spinal dorsal horn neuronal activity.

Single spinal dorsal horn neuronal responses to noxious skin heating or innocuous skin brushing were recorded in pentobarbital anesthetized rats. The heat-evoked activity was selectively abolished by blockade of GABAA receptors in the midbrain periaqueductal grey (PAG) by microinjections of 40 or 400 pmol bicuculline. It is concluded that antinociceptive output neurons in the PAG that trigger descending inhibition are maximally active when released from tonic GABAergic inhibition.

B vitamins suppress spinal dorsal horn nociceptive neurons in the cat.

To explore the role of vitamin B in neural mechanisms of analgesia, we investigated the effect of a compound of vitamins B1, B6 and B12 (Neurobion, E. Merck) on the nociceptive responses of single neurons in the spinal cord dorsal horn in anesthetized cats. Intrathecal superfusion of Neurobion, using a small pool placed on the spinal surface, produced a significant dose-dependent depression in the responses evoked by noxious skin heating (50 or 52 degrees C, 10 s) of hindfoot skin, but not of spontaneous activity in dorsal horn neurons. These results indicate that the therapeutic effect of vitamin B compounds in the clinical management of pain may involve a suppression of nociceptive transmission at the spinal level.

Inhibition of spinal nociceptive neurons by excitation of cell bodies or fibers of passage at various brainstem sites in the cat.

The relative contribution of cells of origin and fibers of passage to the inhibition of spinal nociceptive neurons from various brainstem sites is not known. The present study therefore quantitatively compares the descending inhibition produced by focal electrical stimulation which indiscriminatively excites all neuronal elements with the inhibition evoked by glutamate microinjections which selectively excite cell bodies at the same sites within the midbrain periaqueductal gray (PAG) and neighboring lateral reticular formation (LRF) and within the medullary nucleus raphe magnus (NRM). In pentobarbital anesthetized cats extracellular recordings were made from 22 lumbar dorsal horn neurons responding to innocuous mechanical skin stimuli and to noxious radiant heating of the glabrous skin at the ipsilateral hindpaw. Glutamate microinjections (1 microliter, 0.5 M) into 6 of 10 sites within the NRM reduced heat-evoked responses in 6 different cats to 69.2 +/- 3.8% of control. Electrical stimulation (180-600 microA) at the same sites and two additional sites in the NRM reduced responses to 50.0 +/- 8.7% of control. At 4 of 10 sites within the PAG glutamate reduced spinal neuronal responses to heat in 4 different cats to 69.4 +/- 6.1% of control. Electrical stimulation at 3 of the same sites and 6 additional sites within the PAG reduced heat-evoked responses to 52.7 +/- 3.5% of control. Microinjections of glutamate into the LRF failed to affect heat-evoked responses in any of the 8 experiments tested, while electrical stimulation at 6 of the same sites in the LRF reduced neuronal responses to heat to 52.4 +/- 7.1% of control.(ABSTRACT TRUNCATED AT 250 WORDS)