Spinothalamic Neurons Research Articles

Superficial Dorsal Horn of the Adult Human Spinal Cord

Golgi studies in the adult human spinal cord reveal 10 cell types in the first three laminae. Five are Golgi Type II or ipsilateral proprioneurons of short or long range--the latter including Waldeyer cells. Several of the cells in this group have dendrites that help to form interlaminar boundaries on the gray-white boundary. Two of the four cell types in Lamina II have dendritic fields that correspond exactly to the primary afferent terminal axonal fields described in the cat by Rethelyi (1977). Three cell types, one in each lamina, can be tentatively homologized with monkey spinothalamic cells described by other authors. Our previously described classification method based on dendritic patterns suggests that the Golgi Type II interneurons and ipsilateral proprioneurons belong to two different cell families (and Waldeyer cells to a third), whereas the putative spinothalamic neurons are all different cell types.

Raphe magnus inhibition of primate T 1-T 4 spinothalamic cells with cardiopulmonary visceral input

Effects of stimulation of nucleus raphe magnus on upper thoracic spinothalamic tract neurons were determined. Experiments were performed on 15 monkeys ( Macaca fascicularis) anesthetized with α-chloralose. Forty-two T 1−T 4 spinothalamic tract neurons with viscerosomatic inputs were studied. Stimulation of nucleus raphe magnus inhibited activity of all 42 neurons. Thirty-two of these cells had background activity. The magnitude of the inhibition of background activity was related to the raphe magnus stimulus current. Current strengths as low as 300 μA (100 Hz, 0.2 msec duration) completely inhibited most cells. Current thresholds averaged 80 ± 10 μA and were unrelated to the type of somatic or visceral input the cell received, or to the cell location. Conditioning stimuli applied to nucleus raphe magnus inhibited cell responses to electrical stimulation of cardiopulmonary sympathetic Aδ and C afferent fibers. However, in order to demonstrate preferential inhibition of responses to C fiber input it was necessary to use 200 msec trains of raphe stimuli which were concurrent with the cell response to sympathetic afferent stimuli. Twenty-five spinothalamic neurons were tested for responses to intracardiac injections of bradykinin and 17 cells increased their discharge rate. Stimulation of nucleus raphe magnus (280 ± 25 μA) near the peak of the response reduced activity of all 17 cells from 26 ± 3 to 4 ± 1 spikes/sec ( P < 0.001). Raphe stimulation inhibited responses of 41 of 41 cells to noxious pinch and responses of 15 of 15 wide dynamic range and the 1 low threshold cell to blowing hair. The results establish the capacity of the raphe-spinal pathway to modulate activity of upper thoracic spinothalamic tract neurons including their response to potentially noxious cardiac stimuli. It is therefore possible that descending inhibitory systems may modulate ascending information related to cardiac pain and perhaps account for myocardial ischemic attacks which occur without pain.

Responses of thoracic spinothalamic and spinoreticular cells to coronary artery occlusion.

Spinothalamic and spinoreticular neurons in the C8-T5 spinal segments were examined for responsiveness to occlusion of the left main, left circumflex (CX), or left anterior descending (LAD) coronary artery in monkeys and cats. Four types of cell response to occlusion were observed, as follows: 1) cell activity increased (6 responses) or decreased (1 response) to myocardial ischemia produced by the occlusion; 2) cell activity increased at the onset of occlusion, adapted, and then increased again as ischemia developed (6 responses); 3) cell activity increased at the onset or release of occlusion, and rapidly adapted (13 responses) or remained elevated throughout the occlusion (2 responses); and 4) no response to occlusion (14 tests). Among the types of responses to occlusion, both the magnitude of increased cell activity as well as the spontaneous discharge rates were similar. There were no differences in types of response according to coronary artery ligated. Fourteen cells were tested for responses to separate occlusions of the LAD and CX. Ten cells responded differently to the two occlusions, and four cells exhibited similar responses. C-fiber input onto a neuron was significantly related to whether a cell exhibited a response to cardiac ischemia. Since every cell with C-fiber input did not respond to ischemia, however, this input was not sufficient to predict whether a cell would respond to ischemia. All cells had somatic fields, and all cells responded to noxious stimulation of the somatic field. Some cells also received input from hair movement. The modality of the effective somatic stimulus was not related to type of response to coronary artery occlusion. Spinothalamic and spinoreticular neurons responded similarly to occlusion. Type of response was neither related to cell location in spinal cord nor to projection site in brain. We conclude that spinothalamic and spinoreticular neurons respond to coronary artery occlusion. Different neurons may receive input from different regions of the heart as well as from different types of visceral afferents, resulting in various responses to occlusion. The population of cells excited from ischemia of a given portion of myocardium may determine how the brain interprets the noxious information and refers pain to different somatic structures.

Greater splanchnic excitation of primate T1-T5 spinothalamic neurons.

Effects of electrical stimulation of the left greater splanchnic nerve (SPL) on T1-T5 spinothalamic (STT) neurons were determined. Eighty-five STT neurons were studied in 36 anesthetized monkeys (Macaca fascicularis). All neurons were excited by manipulation of their somatic receptive fields and by electrical stimulation of cardiopulmonary (CP) sympathetic afferent fibers. SPL stimulation excited 63 (74%) STT neurons. There was an increasing percentage of cells with SPL input at more caudal segments and in deeper laminae. Both SPL and CP sympathetic stimulation elicited early or both early and late responses. Latencies to cell activation were usually shorter for CP sympathetic stimulation than for SPL stimulation (5.4 +/- 0.8 versus 11.3 +/- 2.0 ms for early responses and 44.2 +/- 4.2 versus 111.0 +/- 6.6 ms for late responses). The maximum number of spikes per SPL or CP sympathetic stimulus was determined. In the T2 and T3 segments, early responses to CP sympathetic stimulation were significantly greater. However, at more caudal segments, responses to CP sympathetic input decreased while responses to SPL input increased until at T4 there was no difference in the two responses. In T5, responses to SPL input were greater. No differences in the magnitudes of late responses were observed in any of the segments. The response of six cells to SPL stimulation was inhibited by a train of conditioning stimuli applied to the left thoracic vagus nerve. Maximum inhibition occurred at a CT interval of 50 ms and test responses were significantly reduced at CT intervals as great as 200 ms. Bilateral vagotomy eliminated the inhibitory effect. Cutting the left sympathetic chain between the T5 and T6 rami communicantes eliminated 27% of the response to SPL stimulation. More caudal cuts reduced the response further until 71% of the response was abolished by a cut between T8 and T9. Lesions in the dorsolateral column of the spinal cord had little effect on the responses, while lesions of the lateral and ventrolateral columns reduced or abolished the responses. We conclude that SPL stimulation excites T1-T5 STT neurons by way of extraspinal and intraspinal pathways. SPL information is integrated with information from a variety of other visceral and somatic sources. SPL input to cells with somatic fields in the chest region may explain the clinical phenomenon of chest pain associated with abdominal disorders.

Vagal afferent inhibition of spinothalamic cell responses to sympathetic afferents and bradykinin in the monkey.

Effects of stimulating the left thoracic vagus nerve on the responses of spinothalamic neurons to electrical stimulation of cardiopulmonary sympathetic afferent fibers and to intracardiac injections of bradykinin were determined. Experiments were performed on 39 monkeys (Macaca fascicularis) tranquilized with ketamine and anesthetized with alpha-chloralose. The 30 spinothalamic cells studied had the following characteristics. They were excited by manipulation of their somatic receptive fields, were excited by electrical stimulation of cardiopulmonary sympathetic afferent fibers, and exhibited viscerosomatic convergence. Responses of 15 of 19 cells to sympathetic afferent test stimuli were inhibited by conditioning stimuli applied to left thoracic vagus nerve. A conditioning-test interval of 40-50 msec resulted in maximal inhibition of responses to both A delta and C fiber sympathetic afferents. A long time course of inhibition was present to at least a conditioning-test interval of 200 msec. Left thoracic vagus nerve stimulation inhibited 14 of 14 cells responding to intracardiac injection of bradykinin. Entrainment of activity of five cells to the cardiac cycle occurred in response to bradykinin. In each case, left thoracic vagus nerve stimulation, in addition to reducing frequency of cell discharge, disrupted the cardiac related pattern of cell activity. Bilateral cervical vagotomy abolished all inhibitory effects of left thoracic vagus nerve stimulation. These results demonstrate that vagal afferents may participate in processing of information related to cardiac pain.

Diffuse noxious inhibitory controls (DNIC) involve trigeminothalamic and spinothalamic neurones in the rat.

Fifty-eight lumbar dorsal horn and trigeminal nucleus caudalis neurones which could be activated by both innocuous and noxious peripheral stimuli have been recorded in the anaesthetized rat. Using transcutaneous electrical stimulation to produce A and C fibre activity in these neurones from the hindpaw or facial receptive fields the ability of a distant noxious (mechanical or thermal) stimulus applied to the nose, tail, ears and paws to inhibit the neuronal activity was demonstrated. These effects have been termed diffuse noxious inhibitory controls (DNIC). DNIC produced powerful long-lasting inhibitions on all units studied in accordance with our previous results. Approximately 40% of these convergent neurones could be antidromically activated from the contralateral ventrobasal thalamus. Similar neuronal characteristics, effects of DNIC and proportions of projection cells were found in both the dorsal horn and trigeminal complex. However, the spinothalamic tract cells conducted more rapidly than the trigeminothalamic neurones. These results indicate that DNIC can produce comparable effects on the thalamic representation of the efferent activity of these spinal cord and trigeminal neurones. The possible role of DNIC in nociception is discussed.

Responses of thoracic spinothalamic neurons to intracardiac injection of bradykinin in the monkey.

Bradykinin stimulates afferent fibers arising in the heart and may be involved in the mediation of anginal pain and the pain associated with myocardial infarction. The sensation of pain requires that noxious information reach the brain. The purpose of the present study was to determine whether the spinothalamic tract is involved in transmitting noxious information from the heart to the brain. Bradykinin was injected (0.3-3.5 micrograms/kg) into the heart via a catheter in the left atrium while we recorded from single spinothalamic cells in the C8 to T5 spinal segments. Thirty-one of 41 cells responded to bradykinin. The responses of 12 cells were characterized by both an increase in discharge rate and entrainment of cell activity with the cardiac cycle. Eighteen cells responded with only an increased rate, and one cell exhibited only entrainment of cell activity with the cardiac cycle. The mean onset of increased cell activity occurred 15 seconds following drug injection, and the average duration of the response was 54 seconds. Thirty cells increased their mean discharge rate from 11 +/- 2.5 to 29 +/- 4.4 spikes/second. Thus, some spinothalamic cells probably received input from both mechanosensitive and chemosensitive afferents. Tachyphylaxis to repeated doses of bradykinin was observed in 41% of cells. Cells responding to bradykinin had a spontaneous discharge rate that was significantly greater than that of nonresponding cells. Cells did not require input from C-fiber afferents to respond to bradykinin. No statistically significant relationships were found among anatomical locations (laminae and segments) and responses to bradykinin, although cells in lamina I seemed to be less responsive than more ventrally located cells. We conclude that the spinothalamic tract may be involved in the sensation of cardiac pain.

Responses of primate spinothalamic neurons located in the sacral intermediomedial gray (stilling's nucleus) to proprioceptive input from the tail

Extracellular and intracellular recordings were obtained from 24 spinothalamic neurons located in the intermediomedial gray (Stilling's nucleus) in the S2 and S3 spinal segments of anesthetized adult monkeys ( Macaca fascicularis). Most units were spontaneously active. They lacked cutaneous receptive fields but could be excited by subcutaneous receptors. Bending the tail to one side of the animal's body axis excited cells located on the contralateral side of the cord and inhibited ipsilateral cells. The firing rate of each cell was a reproducible function of the angle of the portion of the tail distal to the innervated segment. Cells responded with a burst of spikes to electrical stimulation of low threshold ipsilateral primary afferent fibers in the homosegmental dorsal root. The latency of the underlying synaptic potential was 0.5–0.7 from the time of arrival of the afferent volley at the cord, indicating monosynaptic input. Low intensity stimulation of the contralateral homosegmental dorsal root inhibited background activity. The latency of the underlying inhibitory synaptic potential was 0.8–1.1 ms, suggesting crossed disynaptic inhibition. We conclude that sacral spinothalamic tract neurons located in the intermediomedial gray participate in signalling the spatial orientation of the animal's tail.

Characteristics of primate spinothalamic tract neurons receiving viscerosomatic convergent inputs in T3-T5 segments.

Characteristics of primate spinothalamic tract neurons receiving viscerosomatic convergent inputs in T3-T5 segments.

Convergence of cutaneous and pelvic visceral nociceptive inputs onto primate spinothalamic neurons

The responses of 66 primate spinothalamic neurons to natural stimulation the the urinary bladder and testicle were studied with extracellular recording techniques in order to elucidate the neural basis for referral of visceral pain. Thirty-eight out of 53 cells located at the thoraco-lumbar junction or in sacral segments responded to noxious cutaneous stimuli, and 84% of these also exhibited phasic and/or tonic excitatory responses to distension of the urinary bladder. Seventeen out of 20 of these units, all located at the thoraco-lumbar junction, were excited by compression of the ipsilateral testicle. The response was graded with the compressive force. Excitatory responses to noxious heat and an irritant chemical (KC1) applied to the exposed testicular surface were also observed. Twelve sacral units having inputs from deep receptor of the tail exhibited mixed excitatory and inhibitory responses to bladder distension. A further 2 cells located at the thoracolumbar junction responded only to cutaneous tactile stimuli, and 13 cells located at the lumbosacral enlargement were tonically inhibited by bladder distension. It is concluded that spinothalamic neurons that convey nociceptive input from the skin may also respond to noxious visceral stimuli. Such viscero-somatic convergence provides a neural substrate for the phenomenon of cutaneous referral of visceral pain.

Rostrocaudal and laminar distribution of spinothalamic neurons in the high cervical spinal cord of the cat

In the cat, retrogradely labelled spinothalamic tract cells were found in contralateral medial laminae VI and lateral laminae VII–VIII and ipsilateral lateral laminae VII–VIII and medial laminae VI of the C1, C2, C3 and C4 segments. The proportion of cells in each ipsilateral laminae was similar in each segment but the proportion in contralateral medial laminae VI decreased while the proportion in contralateral laminae VII–VIII increased caudally.

Descending inhibition of spinal neurons in the cardiopulmonary region by electrical stimulation of vagal afferent nerves

Neurons in the left upper thoracic spinal cord of cats anesthetized with chloralose and relaxed with succinylcholine were activated by electrical stimulation of sympathetic chains or by pinching of the skin. Most neurons were spontaneously active, and 22 of the 51 neurons studied were antidromically activated from the spinomedullary junction, demonstrating their projection to higher centers. Stimulation of the central cut ends of either cervical vagus resulted in inhibition of firing in 26 neurons, acceleration in 6 neurons, both effects in 2 neurons, and no effect in the remaining 17 neurons. The parameters of stimulation determined whether inhibition or facilitation was produced in the two neurons that showed either effect. Two spinal neurons were fired by vagal stimulation with latencies of 16 and 20 msec. Activity in vagal afferent fibers is believed to impinge upon brain stem structures that have been shown by others to cause descending inhibition (and facilitation) of spinothalamic and spinoreticular neurons. This would provide a mechanism for modulation of sensory information from the cardiopulmonary region.

Effects of stimulating in raphe nuclei and reticular formation on response of spinothalamic neurons to mechanical stimuli

Effects of stimulating in raphe nuclei and reticular formation on response of spinothalamic neurons to mechanical stimuli

Postsynaptic inhibition of primate spinothalamic neurons by stimulation in nucleus raphe magnus

Postsynaptic inhibition of primate spinothalamic neurons by stimulation in nucleus raphe magnus

Effects of peripherally and centrally administered serotonin on primate spinothalamic neurons.

Serotonin has actions at several different levels of the neural system responsible for nociception. When injected into the arterial circulation of a muscle, serotonin excites small myelinated and unmyelinated fibers supplying nociceptors (Mense & Schmidt, 1974; Fock & Mense, 1976; Mense, 1977). Serotonin is thus an algesic agent in terms of its peripheral action. By contrast, serotonin is thought to be one of the synaptic transmitters in the central nervous system pathways that mediate stimulation-produced analgesia (Akil & Mayer, 1972; Akil & Liebeskind, 1975; Yaksh, 1979; Yaksh & Wilson, 1979).

Spinothalamic and spinomedullary neurons in macaques: A single and double retrograde tracer study

The location and perikaryal size of spinothalamic cells and of spinal neurons projecting to the dorsal column nuclei has been compared in adult monkeys ( Macaco fascicularis) in which horseradish peroxidase has been injected in either the ventrobasal complex or the dorsal medulla. Spinothalamic neurons are found mainly in lamina I and in the lateral portions of laminae IV-VI throughout the side of the cord contralateral to the thalamic injection. Spinomedullary neurons are most ipsilateral to the medullary injection, in medial portions of laminae IV-VI throughout cervical levels but laterally, in the same laminae, in lumbar segments. At these levels, spinothalamic and spinomedullary neurons are also found along the lateral border of the ventral horn; neurons in this location, labelled by either injection, are large (40–65 μm in diameter), and are indistinguishable from ‘spinal border cells’ at the origin of the ventral spinocerebellar tract. Computer-assisted measurement of perikaryal size reveals that the mean values for dorsal horn neurons of the two systems differ significantly, although a sizeable fraction of both neuronal populations have identical cytological characteristics, including perikaryal size. A double-labelling strategy employing horseradish peroxidase and [ 3H]-apo-horseradish peroxidase has been applied (a) to identify simultaneously cells of origin of the two ascending systems and to appreciate better their topographical relationships, and (b) to answer the question of whether at least some of these spinal neurons have axons which, by way of collateral branching, reach both targets. The distribution of neurons at the origin of the two ascending tracts in animals with injection of the two tracers is identical to that revealed in animals in which only horseradish peroxidase has been injected. While primarily single-labelled neurons are found throughout the cord, some large dorsal horn neurons in both brachial and lumbosacral enlargements are labelled by both cytoplasmic horseradish peroxidasepositive granules and by reduced silver grains on the overlying emulsion. These double-labelled cells are interpreted as having an axon which gives origin, presumably at spinal cord levels, to collaterals ascending to both the ipsilateral medulla and the contralateral thalamus. Systematic evaluation of the extent to which ascending pathways to various supraspinal targets originate from common spinal neurons may provide new insights into the functional mechanisms of ascending spinal systems.

Spinothalamic neurones in the cat: some electrophysiological observations

Spinothalamic neurones in the cat: some electrophysiological observations

Excitability changes in lumbosacral spinothalamic neurons produced by non-noxious mechanical stimuli and by graded electrical stimuli applied to the face

The changes in the excitability of lumbosacral spinothalamic neurons produced by activating afferents in the trigeminal nerve using electrical or mechanical stimuli was investigated in cats anesthetized with alpha-chloralose. In most spinothalamic neurons, weak electrical stimuli or step identations of the skin of the face produced an increase followed by decrease in the excitability of these cells. In experiments in which the effect of activating specific groups of trigeminal afferent fibers on these excitability changes was evaluated, the suppression could be produced by activating only the fastest conducting cutaneous afferent fibers. Step indentations of the facial skin affected the excitability of spinothalamic neurons in a manner similar to electrical stimuli. The duration of the suppression phase appeared to be largely independent of the duration of the step identation of the facial skin. It was concluded that the descending system mediating the suppression phase is activated largely by cutaneous afferents from rapidly adapting receptors. The effects of subtotal spinal cord lesions on the excitation and suppression phases produced by facial stimulation indicate that the pathways mediating the suppression descend bilaterally in the dorsal part of the lateral fasciculus. The excitation phase appears to be mediated largely by pathways in the dorsal part of the ipsilateral lateral fasciculus.

Excitation of primate spinothalamic neurons by cutaneous C-fiber volleys.

1. The responses of spinothalamic tract cells in the lumbosacral spinal cords of anesthetized monkeys were examined following electrical stimulation of the sural nerve or the application of noxious thermal and mechanical stimuli to the skin on the lateral aspect of the foot. 2. The spinothalamic tract neurons were classified as wide dynamic range (WDR), high-threshold (HT), or low-threshold (LT) cells on the basis of their responses to mechanical stimuli. 3. All of the WDR and HT spinothalamic tract cells tested responded to volleys in A- and C-fibers. However, strong C-fiber responses were more common in HT than in WDR cells. 4. The responses atributed to C-fibers were graded with the size of the C-fiber volley. The latencies of the responses attributed to C-fibers indicated that the fastest afferents involved had a mean conduction velocity of 0.9 m/s. The responses remained after anodal blockade of conduction in A-fibers. 5. Temporal summation of the responses of spinothalamic tract cells was demonstrated both to brief trains of stimuli at 33 Hz and to single stimuli repeated at 1- to 2-s intervals. The latter phenomenon is often called "windup." 6. The responses of several spinothalamic tract cells to noxious heat pulses could still be elicited during anodal blockade of conduction in A-fibers. Similarly, it was possible to demonstrate an excitatory action of noxious mechanical stimuli despite interference with conduction in A-fibers by anodal current. 7. The cells investigated were located either in the marginal zone or in the layers of the dorsal horn equivalent to Rexed's laminae IV-VI in the cat. The cells were generally activated antidromically from the caudal part of the ventral posterior lateral nucleus of the thalamus.

Responses of primate spinothalamic neurons to graded and to repeated noxious heat stimuli.

1. The responses of primate spinothalamic tract cells innervating the glabrous skin of the foot to noxious thermal stimuli have been examined. 2. Of the 41 cells studied, 98% responded to noxious thermal stimuli. Heating the cutaneous receptive field with a series of stimuli from 35 to 43, 47, and 50 degrees C produced a graded increase in discharge rate. The responses were characterized by an onset, which occurred after the temperature change had either slowed or stopped, an acceleration in the discharge up to a peak, and then an adaptation to a new base-line level. The time constants of adaptation were faster than those reported for C polymodal nociceptors. 3. No systematic differences were found in the responses to noxious thermal stimuli of cells with wide dynamic range receptive fields and of cells with narrow dynamic range, high-threshold receptive fields. There were also no differences in the responses of cells located in the marginal zone and of cells located in the neck of the dorsal horn. 4. The relationship between peak frequency and final skin temperature with a 30 s stimulus duration can best be described by a power function with an exponent of 2.1. An increase in the stimulus duration to 120 s resulted in an increase in the exponent of the power function to 3.2. 5. Repetition of the series of 30-s heat stimuli resulted in an increase in peak frequency, total impulse count, and background activity. Repetition of stimuli having a duration of 120 s produced an increase in the peak frequency at 43 and 45 degrees C, a smaller increase at 47 degrees C, and a decrease at 50 degrees C. Background activity was increased by the lower temperature stimuli, but was decreased following higher temperature stimuli. 6. In six additional cells, the skin was heated with three consecutive presentations at each temperature level (43, 45, 47, and 50 degrees C) for 30 s. No change was observed in the peak frequencies of the responses to successive stimuli of the same intensity. However, the exponent of the power function relating the average peak frequency for the six cells to changes in skin temperature was 3.9. This exponent was larger than that seen when two series of graded heat stimuli of 120 s duration were used, indicating more sensitization despite the fact the total time of exposure to noxious heat was less. 7. A role for both high-threshold and wide dynamic range spinothalamic cells in transmitting nociceptive information to the diencephalon is postulated.