Responses of feline raphespinal neurons to urinary bladder distension.

Effects of distending the urinary bladder were studied on extracellular activity of 77 raphespinal neurons in 19 alpha-chloralose anesthetized cats. Neurons were activated antidromically from thoracic spinal cord; recording sites were located in nucleus raphe magnus (NRM). Mean conduction velocity was 48 +/- 2 m/s. Urinary bladder distension (UBD) increased activity in 12 cells and decreased activity in 17 cells. Spontaneous bladder contractions also affected activity in raphespinal neurons responsive to UBD. Noxious pinch stimulus applied to proximal hindlimbs or forelimbs either increased or decreased activity in 28 raphespinal neurons. No cells were excited both by UBD and pinching of skin and deep tissues of the limbs. Thus, excitatory viscerosomatic convergence was not observed with the stimuli tested in raphespinal neurons examined in this study. Urinary bladder input to descending projection neurons in NRM might participate in descending modulation of dorsal horn neurons. In addition, micturition reflexes might be affected by urinary bladder input to these neurons.

Segmental organization of visceral and somatic input onto C3-T6 spinothalamic tract cells of the monkey.

1. Referred pain of visceral origin has three major characteristics: visceral pain is referred to somatic areas that are innervated from the same spinal segments as the diseased organ; visceral pain is referred to proximal body regions and not to distal body areas; and visceral pain is felt as deep pain and not as cutaneous pain. The neurophysiological basis for these phenomena is poorly understood. The purpose of this study was to examine the organization of viscerosomatic response characteristics of spinothalamic tract (STT) neurons in the rostral spinal cord. Interactions were determined among the following: 1) segmental location, 2) effects of input by cardiopulmonary sympathetic, greater splanchnic, lumbar sympathetic, and urinary bladder afferent fibers, 3) location of excitatory somatic field, e.g., hand, forearm, proximal arm, or chest, 4) magnitude of response to hair, skin, and deep mechanoreceptor afferent input, and 5) regional specificity of thalamic projection sites. 2. A total of 89 STT neurons in segments C3-T6 were characterized for responses to visceral and somatic stimuli. Neurons were activated antidromically from the contralateral ventroposterolateral oralis or caudalis nuclei of the thalamus. Cell responses to visceral and somatic stimuli were not different on the basis of the thalamic site of antidromic activation. Recording sites for 61 neurons were located histologically; 87% of lesion sites were located in laminae IV-VII or X. There was no relationship between response properties of the neurons and spinal laminar location. 3. Different responses to visceral stimuli were observed in three zones of the rostral spinal cord: C3-C6, C7-C8, and T1-T6. In C3-C6, urinary bladder distension (UBD) and electrical stimulation of greater splanchnic and lumbar sympathetic afferent fibers inhibited STT cells. Electrical stimulation of cardiopulmonary sympathetic afferents increased cell activity in C5 and C6 and either excited or inhibited STT cells in C3 and C4. In the cervical enlargement (C7-C8), STT cells generally were either inhibited or showed little response to stimulation of visceral afferent fibers. In T1-T6, input from greater splanchnic and cardiopulmonary sympathetic afferent nerves increased activity of STT cells. Lumbar sympathetic afferent input inhibited cells in T1-T2 and had little effect on cells in T3-T6, whereas UBD decreased cell activity in all segments studied. 4. In general, stimulation of somatic structures increased activity of STT neurons in segments that received primary afferent innervation from the excitatory somatic receptive field or in the segments immediately adjacent to these segments. Only input from the forelimb, especially the hand, markedly excited cells in C7 and C8.+

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.

Inhibitory effects of phrenic afferent fibers on primate lumbosacral spinothalamic tract neurons.

Studies were conducted to determine if electrical or mechanical stimulation of phrenic afferent fibers (PHR) would inhibit the activity of lumbosacral spinothalamic tract (STT) neurons. Twelve monkeys were anesthetized, paralyzed, and artificially ventilated. Extracellular action potentials were recorded from 78 STT neurons located in L2-S3 spinal segments. Electrical stimulation of PHR reduced the activity of 65%, did not affect 33%, and excited 1% of STT neurons. Mechanical stimulation of the diaphragm reduced the activity of 63%, did not effect 34%, and excited 1% of lumbosacral STT neurons. Distention of the urinary bladder (UBD) inhibited 52%, did not affect 23%, excited 23%, and elicited a biphasic response in 1% of STT neurons. However, there was no correlation between the effect of PHR and UBD or somatic classification of the neurons. We conclude that electrical or mechanical stimulation of PHR can produce a generalized inhibition of lumbosacral STT neurons. This inhibitory effect of PHR is similar to inhibitory effects reported for a variety of other afferent systems.

Convergence of phrenic and cardiopulmonary spinal afferent information on cervical and thoracic spinothalamic tract neurons in the monkey: implications for referred pain from the diaphragm and heart.

1. Spinothalamic tract (STT) neurons in the C3-T6 spinal segments were studied for their responses to stimulation of phrenic and cardiopulmonary spinal afferent fibers. A total of 142 STT neurons were studied in 44 anesthetized, paralyzed monkeys (Macaca fascicularis). All neurons were antidromically activated from the ventroposterolateral nucleus and/or medial thalamus. 2. Electrical stimulation of phrenic afferent fibers (PHR) excited 43/58 (74%), inhibited 2/58 (3%), and did not affect 13/58 (13%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of PHR than were neurons with somatic fields confined to the distal limb. Mechanical stimulation of PHR by probing the exposed diaphragm excited 11/22 (50%), inhibited 3/22 (14%), and did not affect 8/22 (36%) cervical STT neurons. 3. The technique of minimum afferent conduction velocity (MACV) was used to obtain information about the identity of the PHR that excited 35 cervical STT neurons. Evidence was obtained for excitation of these neurons by group II and III PHR. The mean +/- SE MACV for all neurons was 14 +/- 2 m/s. 4. Electrical stimulation of cardiopulmonary spinal afferent fibers excited 41/57 (72%), inhibited 8/57 (14%), and did not affect 8/57 (14%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of cardiopulmonary spinal afferents than were neurons with somatic fields confined to the distal limb. 5. Excitatory convergence of PHR and cardiopulmonary spinal afferent input was observed for 36/57 (63%) cervical STT neurons. 6. Electrical stimulation of PHR excited 36/84 (43%), inhibited 25/84 (30%), and did not affect 23/84 (27%) of thoracic STT neurons. All of these neurons received excitatory cardiopulmonary spinal afferent input. 7. Neurons were more likely to be excited by electrical stimulation of PHR if they were located in C3-C6 spinal segments. Furthermore, the net excitatory effect of PHR input decreased in more caudal segments, such that thoracic STT neurons were weakly excited relative to cervical STT neurons. 8. We conclude that cervical STT neurons with excitatory somatic fields that include or are restricted to proximal sites are excited by electrical or mechanical stimulation of PHR. Those effects demonstrate a physiological substrate for pain referred from the diaphragm to the shoulder in patients with pleural effusions or subphrenic abscesses.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiovascular responses to static exercise in man: central and reflex contributions.

1. To assess the contributions of muscle chemoreflexes and central signals of motor command to cardiovascular to static exercise, blood pressure and heart rate were measured during three separate conditions: (i) isometric handgrip contractions, (ii) entrapment of metabolites produced by these contractions within the contracting muscles (chemoreflex effect), and (iii) attempted contractions of acutely paralysed muscles at three levels of effort (command effect). 2. The chemoreflex was assessed during circulatory occlusion applied as the contraction ceased. Paralysis was produced by local infusion of lignocaine distal to a sphygmomanometer cuff inflated above systolic pressure. 3. Blood pressure and heart rate increased progressively during isometric contraction of 33 and 50% maximal voluntary strength (for 120 and 75 s respectively). Muscle chemoreflexes during occlusion also increased blood pressure in proportion to the duration of contraction but did not increase heart rate. During attempted contraction of paralysed muscles at three measured levels of motor command, blood pressure and heart rate increased, but only heart rate was graded with the level of command. 4. The pattern of cardiovascular response for the muscle chemoreflex (as indicated by the ratio of the changes in heart rate and blood pressure) differed from that for isometric contractions and for motor commands in isolation. The pattern for contractions and for moderate but not high intensities of motor command was similar. 5. These data suggest that cardiovascular responses to moderate intensities of static contraction can be produced primarily by motor command, but that both motor command and muscle chemoreflexes contribute to cardiovascular responses at higher intensities of static exercise. When studied in isolation, central motor command and muscle chemoreflexes do not produce the same pattern of circulatory responses.

Urinary bladder and hindlimb stimuli inhibit T1-T6 spinal and spinoreticular cells.

Upper thoracic spinal neurons are primarily excited by cardiopulmonary spinal afferent input but are excited and inhibited by splanchnic afferent input. These data suggest that the greater the number of segments between a spinal neuron and spinal afferent input the greater the probability that the afferent input will inhibit the spinal neuron. Based on this idea we hypothesized that visceral (urinary bladder) and somatic (hindlimb) afferent input would inhibit upper thoracic spinal neurons. To test this hypothesis the activities of 69 spinal and 27 spinoreticular tract neurons in 45 alpha-chloralose-anesthetized cats were studied. Only neurons excited by both visceral and somatic thoracic afferent input were studied. Urinary bladder distension (UBD) inhibited 48 (50%), excited 6 (6%), and did not affect 41 (43%) of these neurons. Also, UBD inhibited the excitatory responses of these cells to noxious visceral and somatic stimuli. Hindlimb pinch also inhibited greater than 50% of the neurons. These data indicate that visceral and somatic afferent input to the lumbosacral spinal cord inhibits the activity of upper thoracic neurons. This inhibitory effect may play a role in localization of sensory and motor responses to noxious stimuli.

Cardiac and abdominal vagal afferent inhibition of primate T9-S1 spinothalamic cells.

Effects of electrically stimulating vagal afferents were determined on lumbosacral spinothalamic tract (STT) neurons in the T9-S1 segments. Stimulating left or right vagal afferents inhibited 20 (50%) and excited 4 (10%) of 40 STT neurons. Vagal stimulation reduced activity of the 20 inhibited cells by 71 +/- 6% and reduced the average activity of all 40 STT neurons by 28% from 11.5 +/- 1.3 to 8.3 +/- 1.4 impulses/s (P less than 0.01). Effects of activating thoracic and abdominal or just abdominal vagal afferents were also determined. Stimulating right abdominal vagal afferents inhibited 4 (11%), excited 1 (3%), and did not affect 30 (86%) of the STT neurons and overall did not significantly affect STT cell activity. In contrast, in 33 of these cells stimulation of afferents in the right cervical vagus inhibited 16 (48%), excited 2 (6%), and did not affect 15 (45%) neurons and overall significantly reduced cell activity by 29% (P less than 0.01). These data and those of Ammons et al. (J. Neurophysiol. 50: 926-940, 1983; Circ Res. 53: 603-612, 1983; J. Neurophysiol. 54: 73-89, 1985) suggest that cardiopulmonary but not abdominal vagal afferent input reduces STT cell activity in many spinal segments. This inhibitory vagal reflex may play a role in protecting the heart.

Urinary bladder and hindlimb afferent input inhibits activity of primate T2-T5 spinothalamic tract neurons.

1. Extracellular recordings were made from 41 spinothalamic tract (STT) neurons on the left side of the T2-T5 spinal segments of 20 monkeys (Macaca fascicularis) anesthetized with alpha-chloralose. Manipulation of the left triceps-chest region and electrical stimulation of cardiopulmonary sympathetic afferent fibers excited these cells. 2. Isotonic urinary bladder distensions (UBD) to pressures between 20 and 80 cmH2O reduced the spontaneous activity in 33 of 41 cells. Cell activity was significantly reduced by UBD at 20 cmH2O. Distensions to 40, 60, and 80 cmH2O produced progressively greater reductions in spontaneous discharge. Activity was decreased throughout distension in 29 cells (tonic inhibition) and at the onset of distension in 3 neurons (phasic inhibition). In one cell, inhibition followed a brief excitation at the onset of distension (phasic excitation-tonic inhibition). Spontaneous bladder contractions also inhibited STT cell activity. 3. Inhibition by UBD was observed in STT cells characterized as wide dynamic range, high threshold, and high threshold inhibitory. No correlation existed between cell type or laminar location and inhibition by urinary bladder distension. Cells excited by cardiopulmonary sympathetic afferent A delta- and C-fibers had a significantly greater tendency to be inhibited by UBD (17 of 18) than cells activated by A delta- but not C-fibers (13 of 20). 4. Urinary bladder distension and pinch of the hindlimbs also reduced activity of STT cells excited by input from cardiopulmonary sympathetic afferents and from the proximal forelimb. 5. Urinary bladder distension to 40, 60, or 80 cmH2O produced a greater absolute but smaller relative reduction in the firing frequency of STT cells as spontaneous activity increased. Thus the magnitude of this inhibitory effect may depend on whether the inhibitory effect is measured as an absolute or relative change in cell activity. 6. Convergent inhibitory input from somatic regions also was observed. Noxious pinch of the hamstring region of the right hindlimb decreased activity in 32 of 39 cells. Left hindlimb pinch inhibited 21 of 38 cells, and 15 of 29 cells were inhibited by right triceps pinch. 7. Convergent inhibitory input from the hamstring region of the hindlimbs and from the urinary bladder to upper thoracic STT cells may be important for coding the intensity and location of noxious visceral and somatic stimuli and for organizing the appropriate sequence of motor responses when multiple noxious stimuli are present.

Effects of blood pressure on force production in cat and human muscle.

In anesthetized cats reducing local arterial pressure from 125 to 75 Torr decreased blood flow (53 +/- 5%) and force production (57 +/- 7%) in soleus and medial gastrocnemius. Force was produced in these muscles by aerobic, slowly fatiguing fibers. Similar reductions in arterial pressure did not affect force production in caudofemoralis, which contains mainly fast-fatiguing fibers. In human subjects the electromyogram produced by the ankle extensors during rhythmic constant-force contractions increased as the contracting muscles were raised above the heart during legs-up tilt. This suggests that force production of active muscle fibers at a given level of activation fell with muscle perfusion pressure, thus requiring augmentation of muscle activity to sustain the standard contractions. Because aerobic fibers contributed to these contractions, it appears that force production of human muscle fibers is sensitive to small changes in perfusion pressure and, presumably, blood flow. The critical dependence of developed muscular force on blood pressure is of importance to motor control and may also play a significant role in cardiovascular control during exercise.

Effect of spontaneous exercise on reflex slowing of the heart in decerebrate cats.

Exercise has been shown to reduce the ability of the baroreflex to slow the heart, and signals arising from cerebral cortex may cause this reduction. To test whether signals arising from the cerebral cortex are required to cause this inhibition, reflex slowing of the heart was assessed in decerebrate cats during rest and spontaneous walking. This reflex was quantified by the relation between systolic blood pressure and the subsequent heart beat interval or its inverse, beat to beat heart rate, during transient rises in pressure caused by injections of phenylephrine. Reflex slowing of the heart was reduced during spontaneous exercise compared to rest. Exercise may inhibit reflex cardiac slowing by activating beta-adrenoceptors that inhibit vagal effects on the heart. To test whether activation of beta-adrenoceptors caused the inhibition of reflex cardiac slowing produced by spontaneous walking in these decerebrate cats, the ability of the baroreflex to slow the heart during blockade of beta-receptors by propranolol was tested in 3 cats. Propranolol did not abolish the inhibitory effect of spontaneous walking on this reflex. These data indicate that the cerebral cortex and beta-adrenoceptors are not required for exercise to inhibit reflex cardiac slowing.

Cardiovascular responses and the sense of effort during attempts to contract paralysed muscles: role of the spinal cord.

To determine whether spinal transection affects the cardiovascular response and the sense of effort which accompany attempts to contract paralysed muscles in normal subjects, paraplegic patients tried to contract paralysed leg muscles. During attempted contractions, paraplegic subjects reported a sense of effort but did not change heart rate or blood pressure. However, these subjects had a normal cardiovascular response to handgrip contractions. These data suggest that pathways descending to and arising from the spinal cord below the lesion are required to generate a cardiovascular response but are not necessary for the sense of effort.

Blockade of the pressor response to muscle ischemia by sensory nerve block in man.

Differential nerve block from peridural anesthesia was used to determine a) if the pressor response to muscle ischemia in man is caused by stimulation of small sensory nerve fibers and b) if these fibers contribute to cardiovascular-respiratory responses during dynamic exercise. Four men exercised at 50-100 W for 5 min. Muscle ischemia and a sustained pressor response were produced by total circulatory occlusion of both legs beginning 30 s before the end of exercise and continuing for 3 min postexercise. During regression of full motor and sensory block, motor strength recovered while sensory block continued; the pressor response was blocked as long as sensory anesthesia persisted (two subjects). During blockade of the pressor response, cardiovascular-respiratory responses to exercise gradually returned from augmented to normal (preblock) levels. Sensory blockade was incomplete in two subjects and the pressor response was not fully blocked. We conclude that stimulation of small sensory fibers during ischemia elicits the pressor response, but that these fibers appear not to contribute to cardiovascular-respiratory responses during mild dynamic exercise with adequate blood flow.

Cardiovascular responses to muscle ischemia in man--dependency on muscle mass.

We sought to determine whether the pressor response to exercise-induced muscle ischemia is related to the mass of tissue rendered ischemic. Six men repeatedly exercised for 5 min at a fixed load between 75 and 150 W (bicycle ergometer). Thirty seconds before the end of exercise, circulation to one calf, two calves, one leg, and two legs was arrested with pneumatic cuffs in successive tests with 15-min recovery periods interspersed. Each occlusion was maintained until the 3rd min of exercise recovery. During postexercise occlusion we observed 1) mean arterial pressure (MAP) was elevated in proportion to the mass of ischemic muscle, 2) forearm blood flow (FBF) was elevated during the overlap of occlusion with exercise but did not show a uniform response during the following 3 min of occlusion--either vasoconstriction or vasodilation occurred, 3) heart rate (HR) was elevated only when two legs were occluded, and 4) occlusion did not affect ventilation or endtidal CO2. We conclude that the ischemic pressor response is muscle mass-dependent. Our findings suggest that the baroreflex alters peripheral vascular resistance so as to aid in the maintenance of elevated MAP.