Spinothalamic Neurons Research Articles

Sensory innervation of the viscera: peripheral basis of visceral pain.

Sensory innervation of the viscera: peripheral basis of visceral pain.

Differential effects of SP antagonist, RP-67580, on the C-evoked late discharges of the rat spinothalamic and non-projection neurons

Differential effects of SP antagonist, RP-67580, on the C-evoked late discharges of the rat spinothalamic and non-projection neurons

Spinothalamocortical inputs nonpreferentially innervate the superficial and deep cortical layers of SI

Using a combined anterograde and retrograde tracing technique, we examined the distribution pattern of the thalamocortical cells which projected to superficial layers of the hand region of the primary somatosensory cortex (hSI), and quantitatively analyzed the retrogradely labeled cells which putatively contacted terminals of the spinothalamic tract (STT) in the squirrel monkey and the macaque. Less than 25% of the superficial hSI projecting cells were putatively contacted by terminals of cervical enlargement spinothalamic neurons. These cells were primarily located in ventro-posterior lateral, ventroposterior inferior and centrolateral nuclei. Although the number of superficial hSI projecting cells numbered less than 20% of the total hSI projecting cells, their patterns of location and their proportion of overlap with STT terminals within each thalamic nucleus were similar. It is suggested that the spinothalamic nociceptive information input to the cortex equally accesses both superficial and deep SI.

Chronic effects of topical application of capsaicin to the sciatic nerve on responses of primate spinothalamic neurons

The responses of 144 spinothalamic tract (STT) cells were recorded in 15 anesthetized macaque monkeys ( Macaco fascicularis). Three to 4 weeks prior to the acute experiment, the sciatic nerve was surgically exposed on one or both sides so that capsaicin or vehicle could be applied. Responses of STT cells recorded in 3 experimental groups were compared: untreated (21 cells), vehicle-treated (40 cells), and capsaicin-treated (83 cells). The background activity of cells in the vehicle- and capsaicin-treated groups was the same as in the untreated group (that is, cells on the side contralateral to surgery). Responses to innocuous (BRUSH) and noxious (PINCH) mechanical stimuli were unchanged by vehicle or by capsaicin treatment. However, responses to other noxious (PRESSURE and SQUEEZE) mechanical stimuli were significantly increased in the vehicle-treated group. Compared with a large reference population, all experimental groups showed a significant increase in overall responsiveness to mechanical stimuli (as determined by cluster analysis), greatest in the vehicle-treated group. Responses to noxious heat stimuli were significantly reduced in the capsaicin-treated group for 45°C and 47°C stimuli. Volleys in A fibers, probably Aδ fibers, evoked prolonged responses in many STT cells of all treatment groups. Electron microscopic counts of axons in the sciatic nerves of animals treated with capsaicin showed a reduced number of C fibers but no appreciable loss of myelinated axons. This loss of unmyelinated sensory fibers was presumably responsible for the reduction in the responses of the STT cells to noxious heat stimuli. Increased responses to some noxious mechanical stimuli and to A fiber volleys may have been the consequence of several factors, including surgical manipulation, a chemical action of vehicle and a contralateral action of capsaicin treatment.

Nitric oxide synthase is found in some spinothalamic neurons and in neuronal processes that appose spinal neurons that express Fos induced by noxious stimulation

To determine if nitric oxide (NO) and Fos immunoreactivity induced by noxious stimulation were colocalized in spinothalamic neurons, double-staining immunocytochemical techniques were combined with retrograde neuroanatomical tracing procedures. Initial studies on three rats demonstrated that Fos and nitric oxide synthase (NOS), the synthesizing enzyme for nitric oxide, did not coexist in spinothalamic tract neurons. However, some spinothalamic neurons were found to contain NOS and some NOS immunoreactive processes were found to appose Fos containing neurons. Thus the remainder of the study: (1) analyzed the relationship of NOS positive neuronal processes with Fos stained neurons using a Fos immunocytochemical technique in combination with either NOS immunofluorescence or NADPH-diaphorase histochemistry; and (2) quantitated the number of NOS containing cells that project to the thalamus using a combined immunofluorescent-retrograde tracing procedure. Both NOS-like immunoreactive (NOS IR) neuronal processes and NADPH-diaphorase positive neuronal processes in the dorsal horn of the lumbar spinal cord were found to oppose Fos positive neurons located in laminae I and II of the dorsal horn. Approximately 40% of Fos-labeled cells in these superficial laminae were found to be in apposition to or in close proximity to NOS labeled neuronal processes. Examination of spinal cord section for NOS-containing spinothalamic tract neurons revealed that lamina X was the onyl spinal cord region containing such double-labeled neurons. Further quantification revealed that approximately 10% of NOS positive neurons in lamina X were double-labeled with Fluorogold. These findings support the hypothesis that nitric oxide is involved in nociceptive events occuring in the spinal cord in response to a peripheral noxious stimulus and further indicate that nitric oxide may contribute to the central transmission of spinothalamic information.

Spinothalamic and propriospinal neurones in the upper cervical cord of the rat: terminations of primary afferent fibres on soma and primary dendrites.

Experiments were performed on rats to determine whether primary afferents from the upper cervical region terminate directly on spinothalamic and propriospinal neurones. The central terminations of primary afferents from the upper cervical region were identified by diffusely filling their axons with horseradish peroxidase. Spinothalamic neurones or propriospinal neurones were identified in the same experimental animals by using retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. Approximately 3-11% of spinothalamic cells in laminae 4-6 of spinal segments C2-4 received apparent synaptic contacts from primary afferents on the soma or primary dendrites. Approximately 18-36% of propriospinal neurones with axons descending to lower thoracic or lumbar levels received apparent synaptic contacts on the soma or primary dendrites. These data provide anatomical evidence that spinothalamic and long propriospinal neurones in the upper cervical cord are excited directly by primary afferents. The data also help to clarify the neural circuitry underlying somatic sensation and reflex movements evoked by neck receptors.

Organization of the serotonergic innervation of spinal neurons in rats—I. Neuropeptide coexistence in varicosities innervating some spinothalamic tract neurons but not in those innervating postsynaptic dorsal column neurons

Previous studies have suggested that peptides such as substance P and thyrotropin-releasing hormone coexist with serotonin in the same varicosities in the ventral horn and intermediate gray of the spinal cord in rat. However, coexistence of these peptides with serotonin is rare in fibers in the superficial dorsal horn. Since it has been proposed that serotonergic fibers in the superficial dorsal horn act to modulate nociception, it was hypothesized that the serotonergic neurons that contain neither substance P nor thyrotropin-releasing hormone might constitute a specifically antinociceptive subset of serotonergic neurons. This being the case, it would be expected that different types of serotonergic neurons innervate nociceptive and non-nociceptive spinal neurons. In order to test this hypothesis, a group of cells that include nociceptive neurons (spinothalamic tract neurons) and a group of predominantly non-nociceptive neurons (postsynaptic dorsal column neurons) in the spinal cord of rat were retrogradely labeled. Sections of the spinal cord containing retrogradely labeled spinothalamic tract or postsynaptic dorsal column neurons were stained for serotonin and either substance P or thyrotropin-releasing hormone using two-color immunohistochemistry. A retrogradely labeled cell was classified as “apposed” if there was no discernible distance between an immunohistochemically labeled varicosity and the cell. Eighty per cent of spinothalamic tract and 83% of postsynaptic dorsal column profiles were apposed by serotonin-immunoreactive varicosities in the spinal cord. Thirty-one per cent of the spinothalamic tract profiles that were apposed by serotonergic varicosities were apposed by serotonergic varicosities that were also stained for thyrotropin-releasing hormone. The distribution of the latter spinothalamic neurons was similar to that reported for spinothalamic tract neurons responsive to joint movement. In addition, at least 63% of the spinothalamic tract profiles which were apposed by serotonergic varicosities were apposed by “serotonin-only” varicosities, including most spinothalamic tract neurons in the marginal zone, suggesting that at least some “serotonin-only” neurons are antinociceptive. However, contrary to the hypothesis, at least 94% of the postsynaptic dorsal column profiles apposed by serotonergic varicosities were apposed by “serotonin-only” varicosities. These findings suggest that there may be a relationship between the sensory modality to which a spinal neuron responds and the type of serotonergic innervation it receives. However, it appears that “serotonin-only” neurons may not constitute a specifically antinociceptive category of serotonergic neurons.

Response properties of upper cervical spinothalamic neurons in cats. A possible explanation for the unusual sensory symptoms associated with upper cervical lesions in humans.

Lesions in the foramen magnum and upper cervical spinal cord often cause an unusual array of sensory changes and atrophic weakness, primarily involving the ipsilateral forelimb. Furthermore, small midline myelotomies performed at C1 often lead to widespread analgesia covering most of the body in patients with chronic pain. These observations challenge physicians' understanding of anatomy and physiology in the upper cervical region. Using single cell recording techniques the authors have shown that spinothalamic neurons in the second cervical segment of cats have complex response properties, often responding to stimuli throughout the body. These findings together with a review of clinical and basic science literature are used to provide explanations for the unusual signs and symptoms observed in patients with upper cervical and foramen magnum lesions.

Pain modulation: From a negative to a positive feedback loop?

D escending excitatory systems that modulate spinal nociceptive processing have been demonstrated electrophysiologically and the existence of functional excitatory spinobulbospinal loops has been proposed time and again, not only in reflexology,27*33 but also in the study of pain. In this respect, Giesler and his colleagueslg described a population of lumbosacral spinothalamic neurons in the monkey, which were driven by heterotopic noxious inputs. Stimulation of some bulbar reticular areas produced a profound excitation of these cells and lesions of descending spinal pathways also reduced the size of their excitatory receptive fields. Excitatory spinobulbospinal loops were also demonstrated in the cat by Cervero and Wolstencroft,l” who were able to show reciprocal excitation between descending pathways from reticular areas in the rostra1 ventral medulla (RVM) and spinoreticular neurons. These authors also reported the existence of tonic and phasic descending excitatory influences from bulbar-reticular structures on spinal viscerosomatic nociceptive neurons.34 However, we must seriously debate the question addressed by Howard that is: is there any reason to believe that these systems are not more than just laboratory curiosities and are active under physiological or pathological conditions? In other words, do these systems work naturally, and, if so, how? These are not trivial questions since what is being proposed in

Intracardiac phenylbiguanide causes excitation of spinal neurons by activation of cardiac sympathetic afferents

The responses of spinothalamic, spinoreticular, and unidentified spinal neurons to intracardiac administration of phenyl-biguanide, a 5-HT 3 receptor agonist, were examined in anesthetized cats and monkeys. Eighteen neurons were excited, 5 were inhibited, and 12 were unresponsive to this stimulus. Results suggest that cardiac sympathetic afferents mediate the excitatory responses produced by phenylbiguanide, because bilateral cervical vagotomy failed to block these responses, and aortic injections of phenylbiguanide had little effect on cell activity.

Bowditch Lecture. Renal afferent inputs to ascending spinal pathways.

Studies of renal afferent fibers and their functions have continued since the work of Pines in 1959 (Fiziol. Zh. SSSR Im. I M Sechenova 45: 1339-1347, 1959). The kidney contains mechanoreceptors and chemoreceptors that appear to have two major functions. First, renal mechano- and chemoreceptors evoke a variety of renorenal reflexes, while more global cardiovascular reflexes are primarily evoked by renal mechanoreceptors. A second function of renal afferent fibers is to cause the pain of renal disease. Recent studies suggest that renal afferent fibers may also regulate secretion of vasopressin from the pituitary gland. Substantial evidence indicates that, although most renal afferent fibers enter the spinal cord, their functions depend to a large extent on supraspinal circuitry. Thus our research has focused on defining characteristics of spinal neurons that relay renal information to the brain. In the cat, neurons in the L2-T11 segments with excitatory responses to renal A delta and C fiber input project to the medial medullary reticular formation and to the caudal and rostral ventrolateral medulla. Renal afferent information reaches these cells by way of the least splanchnic nerve and by way of more than one dorsal root. In the monkey spinothalamic neurons in the L3-T10 segments respond to renal nerve stimulation. Excitatory responses predominate, but inhibitory responses occur in L2 and L3. These cells also respond to renal A delta and C fibers. Stimulation of renal mechanoreceptors by occlusion of the ureteropelvic junction or renal vein excites feline spinoreticular neurons. Graded increases in renal vein pressure produce graded increases in cell responses. Activation of renal chemoreceptors increases activity of spinal interneurons. Within the L2-T11 segments, cells responding to ureteral occlusion are located caudally, cells with responses to renal artery occlusion are located rostrally, and cells responding to renal vein occlusion are located in between. The differential locations of cells with these inputs suggests the existence of a coding mechanism for different renal receptor populations. Distention of the renal pelvis is a potent stimulator of primate spinothalamic neurons. These neurons encode renal pelvic pressures in the noxious range and appear to be important in mechanisms of renal pain.

Substance P innervation of the rat and cat thalamus. I. Distribution and relation to ascending spinal pathways.

An antiserum for substance P (SP) with minimal cross-reactivity for other tachykinins was employed to map the distribution of SP-positive nerve fibers and terminals in the thalamus of cats and rats with special emphasis on the innervation by these fibers of nuclei related to the somatosensory system. In both species SP innervation is predominantly along the midline, in medial and posterior thalamic regions, and sparser in sensory relays for specific modalities. Among the most densely innervated nuclei are the parafascicular, paraventricular, rhomboid, central medial and parts of mediodorsal, lateral posterior, and ventral lateral geniculate. SP innervation of somatosensory-related nuclei is also evident in central lateral nucleus, posterior complex (PO), and in ventroposterolateral (VPL) nucleus of both cats and rats. In VPL of cats SP fibers and terminals are present along its ventral and lateral border, a paralaminar area in which spinothalamic fibers have been shown to terminate and where neurons responsive to noxious stimuli have been reported. Also in rats the SP innervation of VPL is similar to that of spinothalamic tract fibers. The SP innervation of somatosensory thalamic nuclei may be supplied, at least in part, by spinothalamic afferent as suggested by the depletion of SP after anterolateral chordotomy but not after ablation of the dorsal column nuclei. The presence of SP-positive spinothalamic neurons in the spinal cord is reported in the following paper.

Enhancement of spinothalamic neuron responses to chemical and mechanical stimuli following combined micro-iontophoretic application of n-methyl- d-aspartic acid and substance P

A role for sensitization of nociceptors in the generation of primary hyperalgesia is well documented. More recent work has begun to define a role of an increased excitability of neurons within the spinal cord in the generation of secondary hyperalgesia. The present study demonstrates increased responses of primate spinothalamic neurons following co-administration of n-methyl- d-aspartic acid (NMDA) and substance P (SP) by micro-iontophoresis. Wide dynamic range and high threshold STT neurons in laminae I-VI showed an increased frequency of discharges following application of NMDA which was characterized by a slow onset to peak discharge rate and a slow return to background levels of discharge. Combined application of NMDA with SP resulted in an enhancement of responses to NMDA that often long outlasted the administration of SP. This increase in response of the cells to NMDA was not produced by repeated application of NMDA alone or following combined application of NMDA with an SP analog. NMDA responses were reduced or prevented in all cases by co-application of an NMDA-receptor antagonist. Finally, long-lasting potentiation of NMDA responses by SP was paralleled by enhanced responses to mechanical stimulation of skin. It is proposed that a mechanism involving the combined synaptic release of excitatory amino acids and peptides leads to secondary hyperalgesia.

Morphine enhances the activity of thermoreceptive cold-specific lamina I spinothalamic neurons in the cat

The possibility that morphine might differentially affect spinal neurons responsive to small-diameter thermoreceptive-specific afferents was tested. Systemic morphine enhanced a portion or all of the stimulus-response function of 7 of 9 lamina I spinothalamic tract cells specifically sensitive to cold applied to the glabrous hindpaw in the cat. This result contrasts strongly with the predominant inhibition of nociceptive lamina I neurons by morphine.

Somatosensory response properties of contralaterally projecting spinothalamic and nonspinothalamic neurons in the second cervical segment of the cat

1. The upper cervical spinal cord contains over one-third of the cells of the spinothalamic tract (STT). This study investigated response properties of contralaterally projecting STT neurons in C2 of the cat by the use of single-unit, microelectrode recordings. Standard antidromic stimulation and collision techniques were used to identify STT units projecting to the contralateral thalamus. Once an STT unit was found, its receptive field (RF) and responses to cutaneous stimuli such as touch, pressure, deep muscle squeeze, tap, noxious pinch, and heat were characterized. C2 units that were not activated from the contralateral thalamus (non-STT units) were also characterized. The locations of thalamic stimulation electrodes and spinal recording sites were reconstructed from electrolytic lesions. 2. A total of 48 STT and 68 non-STT units were well characterized. RF sizes were classified as small, intermediate, large, or whole body. Each unit was also classified as having one of two possible response types: simple units were those with homogeneous responses within the RF and were classified as low threshold (LT), high threshold (HT), wide dynamic range (WDR), deep, or tap. Complex units were those that responded differently in different regions of the RF. 3. The average depth of non-STT units subdivided by RF size was 2.1 +/- 0.6 (SD) mm for cells with small RFs, 2.4 +/- 0.8 mm for cells with intermediate RFs, 2.8 +/- 0.3 mm for cells with large RFs, and 2.7 +/- 0.5 mm for cells with whole-body RFs. The average depth of non-STT units based on response type was 2.0 +/- 0.5 mm for LT, 2.3 +/- 0.7 mm for HT, 2.1 +/- 0.7 mm for WDR, 2.6 +/- 0.9 mm for deep, 2.6 +/- 0.5 mm for tap, and 2.4 +/- 0.2 mm for complex. 4. A somatotopic organization along the rostrocaudal length of C2 and upper C3 was observed for non-STT units with small- and intermediate-size RFs. The average distance of the recording sites from the rostralmost dorsal rootlet of C2 was 3.8 +/- 2.1 mm for units with RFs on the face, 7.1 +/- 4.3 mm for units with RFs on the neck, and 11.9 +/- 5.1 mm for units with RFs on the forelimb. 5. The average threshold for antidromic activation of STT units was 175 +/- 120 microA. Most C2 STT units were activated from the ventroposterior region of the thalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

Intracellular study of electrophysiological features of primate spinothalamic tract neurons and their responses to afferent inputs

1. Intracellular recordings were made from 43 spinothalamic (STT) neurons in the lumbosacral region of the spinal cord in anesthetized macaque monkeys. The antidromic responses of these neurons to electrical stimulation of the ventral posterior lateral (VPL) nucleus of the thalamus were examined, and orthodromic responses to electrical stimulation of the sural nerve or to mechanical stimulation of hindlimb skin were recorded to study the electrophysiological features of these neurons and their responses to afferent inputs. 2. The resting membrane potential of the neurons ranged from -26 to -70 mV and the antidromic latency from 2.3 to 9.1 ms. Three of the neurons were located in lamina 1 and were recorded so briefly that only antidromic and spontaneous activity could be studied. The rest of the neurons were located in laminae III-V and were of the wide-dynamic-range (WDR) type. 3. The antidromic action potentials recorded in the somas of STT neurons typically showed a fast rising phase and a short initial segment-somadendritic (IS-SD) delay. After repetitive antidromic stimulation, a progressive elongation of the IS-SD delay, widening of the spike, and failure of the SD spike were observed. 4. The afterpotential of the antidromic action potential consisted of a fast afterhyperpolarization (AHPf) and sometimes a delayed depolarization (DD) and a slow afterhyperpolarization (AHPs). The amplitude and the duration of the AHPs were progressively increased when longer trains of stimuli were used. When the membrane potential was hyperpolarized, the amplitude of the AHPs decreased, suggesting an involvement of K+ and/or Cl- ions. However, the AHPs completely disappeared when the strength of stimulation was adjusted to a level just below the threshold for the axon, suggesting that it was unlikely that recurrent inhibition contributed to the AHPs. 5. The background activity of 32 STT neurons was analyzed. The membrane potential at which spikes were triggered in these neurons was around -42 mV. The width and the rise time of the spontaneous spikes were shorter than those of antidromic action potentials, although the maximum rate of rise was similar. The heights of the spontaneous spikes were slightly shorter than those of antidromic action potentials. 6. Three types of background activity have been observed. One type had a very low average spontaneous rate with a bursting firing pattern, consisting of a few spikes superimposed on a depolarization. This type of activity was seen mostly in lamina I neurons. The second type of activity had a moderate to high spontaneous rate with a fairly constant interval between spikes.(ABSTRACT TRUNCATED AT 400 WORDS)

Ultrastructural localization of substance P, met‐enkephalin, and somatostatin immunoreactivity in lamina X of the primate spinal cord

The ultrastructural localization of substance P (SP), met-enkephalin (MENK), and somatostatin (SS) in the lamina X area surrounding the central canal of the macaque monkey was examined by the indirect peroxidase-antiperoxidase method. The most common synaptic terminals in lamina X were simple terminals (S) with small rounded or pleomorphic clear vesicles; one to two dense-core vesicles were occasionally also present. These were found on soma, dendrites, and dendritic spines, in all regions of lamina X. A second class of terminal with round or oval clear vesicles was glomerular (G) in shape, with scalloped edges, and contained many mitochondria. These large terminals had several synaptic contacts onto dendrites, spines, and small terminals and were found mainly in the lateral region. The third class (L) contained small clear vesicles and several vesicles with large, dense cores (100-125 nm), and also contacted dendrites, mainly lateral to the canal. The fourth class of terminal (D) contained small clear vesicles and several vesicles with small, dense cores (75-100 nm); these contacted dendrites and somata in all areas. Very few terminals with flat vesicles were identified. There was an unequal distribution of immunoreactivity among the several terminal classes identified in lamina X. Most SP terminals were S terminals, but SP L terminals were also common; few were D terminals. MENK terminals were usually either S terminals or D terminals; L terminals were rarely MENK positive. SS terminals were commonly D terminals or S terminals; L terminals were also rarely SS positive. Only SP terminals were identified as G terminals. Synaptic targets of SP, MENK, and SS terminals were most commonly dendrites. In addition to unlabelled neurons, peptidergic neurons and their processes were also synaptic targets of terminals containing the same peptide. The distributions of these peptides in primate lamina X differ from that of the same peptides in primate superficial dorsal horn. These differences are important, in consideration of some of the parallels that may be drawn between the lamina X area and the superficial dorsal horn; both areas have high concentrations of the same peptides, receive nociceptive primary afferents, and contain spinothalamic and other projection neurons. Nevertheless, comparison of the distribution of immunoreactivity among terminal classes indicates that neurochemical organization at the ultrastructural level is quite distinct in each of the two areas. This may also reflect other roles of the lamina X area, including its involvement in visceral functions, although it would be expected that this element might be less prominent at the cervical levels we investigated.

Modification of the responses of primate spinothalamic neurons to mechanical stimulation by excitatory amino acids and an N-methyl- d-aspartate antagonist

Excitatory amino acids (EAAs) are likely to play a key role in sensory transmission in the spinal cord. In the present study, the microiontophoresis technique was used to investigate the effects of l-glutamate (GLUT), N-methyl- d-aspartate (NMDA), and quisqualate (QUIS), as well as an NMDA receptor antagonist, AP-7, on the discharges evoked in nociceptive primate spinothalamic tract (STT) neurons by mechanical stimulation of the skin. Responses to innocuous brushing of the skin were facilitated by GLUT and NMDA (and in some neurons by QUIS) and sometimes reduced by AP-7. GLUT also facilitated the responses to noxious mechanical stimuli. The results are consistent with anatomical evidence for the presence of synapses that contain EAAs on primate STT cells and with the proposal that the co-release of EAAs and neuropeptides may contribute to hyperalgesia.

Cardiopulmonary sympathetic afferent excitation of lower thoracic spinoreticular and spinothalamic neurons

1. Responses of spinoreticular (SRT) and spinothalamic (STT) neurons located in the T7-T9 segments to cardiopulmonary sympathetic afferent (CPS) stimuli were studied in 27 cats that were anesthetized with alpha-chloralose. 2. CPS stimulation excited 32 SRT and 10 STT neurons. Each neuron was also excited by stimulation of the left greater splanchnic nerve (SPL) and had a somatic receptive field that was most commonly located on the upper abdomen and over the lower rib cage. An additional 12 SRT and 3 STT neurons received input from SPL and somatic structures but failed to respond to CPS stimulation. 3. CPS stimulation evoked early responses (23 cells) or both early and late responses (19 cells) that had average latencies of 12.7 +/- 1.8 and 88.2 +/- 13.1 (SE) ms, respectively. Latencies of responses to SPL stimulation were significantly shorter and averaged 8.1 +/- 0.9 and 46.1 +/- 7.1 ms. Magnitudes of early responses to SPL stimulation were significantly greater than responses to CPS stimulation; however, late responses were not different. 4. Responses to CPS stimulation were inhibited by a prior conditioning stimulus applied to SPL. Greatest inhibition occurred at a conditioning-test interval of 40 ms, and inhibition lasted for at least 300 ms. Inhibition of responses to SPL stimulation could be evoked by conditioning stimuli applied to CPS; however, the inhibition was significantly less than that evoked by SPL stimulation on responses to CPS stimulation. 5. Thirty-eight neurons were tested for responses to injection of bradykinin (4 micrograms/kg) into the left atrium. Discharge rate of 17 cells increased from 5 +/- 2 to 12 +/- 4 Hz. Four cells were tachyphylactic to repeated injections. Injections of bradykinin into the thoracic aorta did not significantly alter cell activity. Bilateral cervical vagotomy had no effect on responses to intracardiac bradykinin. 6. The results indicate that lower thoracic SRT and STT neurons are excited by CPS stimuli including noxious stimulation of the heart. However, comparison of these responses with previously reported responses of upper thoracic SRT and STT neurons indicate that there is a decrease in effectiveness of CPS stimuli from upper to lower thoracic segments. Convergence of CPS and abdominal inputs onto lower thoracic pain pathways could explain abdominal pain that is occasionally associated with cardiac disease.

Direct catecholaminergic innervation of primate spinothalamic tract neurons

Catecholaminergic axonal varicosities identified by immunocytochemical staining for dopamine-beta-hydroxylase were observed at the light microscopic level apposing the somata of retrogradely labeled spinothalamic tract neurons in the monkey spinal cord. Three retrogradely labeled and two intracellularly labeled spinothalamic neurons were serially sectioned and examined at selected intervals at the electron microscopic level. Electron microscopic study revealed that axonal boutons directly contacted the somata and/or dendrites of lamina I, IV, and V spinothalamic tract neurons. All of the profiles apposing one of the retrogradely labeled lamina I spinothalamic tract neurons were categorized from eight planes of section spaced at 1-micron intervals. Of the 305 profiles counted that were adjacent to this soma, 17 (5.6%) stained positively for dopamine-beta-hydroxylase. Of these 17 appositions, three were followed in serial sections to confirm that they had synaptic thickenings and alignment of vesicles along the membrane contacting the spinothalamic tract soma. Catecholaminergic boutons were observed apposing the somata and dendrites of intracellularly filled STT cells characterized as high threshold and wide dynamic range neurons. These observations clearly indicate a direct innervation of spinothalamic tract neurons by catecholaminergic neurons, providing anatomical data to support previous physiological findings demonstrating that catecholamines modulate nociceptive transmission.