Spinothalamic Tract Neurons Research Articles

Morphological classes of spinothalamic lamina I neurons in the cat

We examined the morphology and distribution of retrogradely labeled spinothalamic tract (STT) neurons in lamina I (the marginal zone) of the spinal dorsal horn after large injections of cholera toxin subunit B (CTb) or Fast Blue (FB) into the contralateral thalamus of cats. Based on the shape and orientation of the somata and proximal dendrites in horizontal sections, three distinct cell types were identified: (1) fusiform cells with small, spindle-shaped somata and bipolar, longitudinal dendritic arbors; (2) pyramidal cells with triangular somata and three main dendritic origins with primarily longitudinal arborizations; and (3) multipolar cells with larger, multiangular somata and four or more radiating dendritic arbors directed both longitudinally and mediolaterally. These three morphological types differed significantly in the number of primary dendrites and the size of the somata. Subclasses of multipolar cells were noted. Nearly all cells could be categorized into these three classes consistently in horizontal sections. A small number of cells with transitional shapes or with small, round somata were unclassified. The proportional distributions of these cell types were found to vary over the length of the spinal cord (from the third cervical through the coccygeal segments) in three cats. The overall proportions of cell types were 34% fusiform, 36% pyramidal, 25% multipolar, and 5% unclassified. The proportions of pyramidal and multipolar cells were strikingly higher within the C7-8 and L6-7 segments and lowest in the thoracic segments. In contrast, fusiform cells formed about 20% of the labeled lamina I STT population in the C7-8 and L6-7 segments but more than 60% in thoracic segments. Across all nine cats, the proportions were similar within the cervical (C5-8) and lumbosacral (L5-S1) enlargements, although considerable interanimal variability was noted. These distinct morphological types of lamina I STT cells with differential longitudinal distributions probably have different functional roles. They may correspond to the three main physiological classes of lamina I STT cells.

Somatosensory findings in patients with spinal cord injury and central dysaesthesia pain.

To determine whether central pain in patients with spinal cord injury is only dependent on the lesioning of spinothalamic pathways. In sixteen patients with spinal cord injury and central dysaesthesia pain, somatosensory abnormalities in painful denervated skin areas were compared with somatosensory findings in normal skin areas as well as in non-painful denervated skin areas. The threshold values for detection of thermal (heat, cold, heat pain, or cold pain) and tactile stimulation were significantly changed in denervated skin areas although there were no significant differences in the threshold values between painful and non-painful denervated skin areas. The reductions of sensations of touch, vibration, joint position, and two point discrimination in painful and non-painful denervated skin areas were not significantly different. Allodynia (pain caused by non-noxious stimulation) and wind up-like pain (pain caused by repeatedly pricking the skin) were significantly more common in painful than non-painful denervated skin areas. Because pain and thermal sensory perception are primarily mediated to the brain via spinothalamic pathways, whereas the sensations of touch, vibration and joint position are primarily mediated by dorsal column-medial lemniscal pathways, the results indicate that central pain is not only dependent on the lesioning of either dorsal column-medial lemniscal pathways or spinothalamic pathways. The findings of abnormal evoked pain (allodynia and wind up-like pain) may be consistent with the experimental findings of hyperexcitability in nociceptive spinothalamic tract neurons, that may be involved in the pathogenesis of central pain.

Laminar distribution of the cells of origin of the spinocerebral pathways involved in nociceptive transmission and pain modulation in the rat

The laminar distribution of spinomesencephalic, spinothalamic, and spinotelencephalic tract neurons, and the pattern of axonal collateralization in these spinocerebral pathways were studied in the rat by means of retrograde double-labelling of the cells with fluorescent dyes Fluoro-Gold and Primuline O. We found that sources of spinocerebral pathways to the analgesic brainstem centers, as well to thenucl. accumbens and septal nuclei, were mixed together in the marginal zone (lamina I, by Rexed), in the deep dorsal horn (laminae IV–VI), in the area around the central canal (lamina X), and within the lateral spinal nucleus. At the same time, all the above pathways retain their own specific projection fields. Thus, these spinocerebral projections could be characterized as extensive, but not diffuse. We propose that the main effect of activation of the direct spinal inputs to the limbic system is an increase in nociceptive sensitivity, but not a suppression of nocicptive transmission at the the spinal cord level.

Role of GABA receptor subtypes in inhibition of primate spinothalamic tract neurons: difference between spinal and periaqueductal gray inhibition.

1. gamma-Aminobutyric acid (GABA) is thought to inhibit both pre- and postsynaptically the transfer of nociceptive signals from primary afferent fibers to spinal dorsal horn sensory cells, including spinothalamic tract (STT) neurons. The inhibition can be mediated by both GABAA and GABAB receptors. We now attempt to characterize the synaptic inhibition of STT cells by spinal GABAA and GABAB receptors in anesthetized monkeys and to analyze the roles of these two receptor subtypes in the inhibition of STT cellular activity produced by stimulation in the periaqueductal gray (PAG). 2. Iontophoretic release of GABA or muscimol (a selective GABAA receptor agonist) onto STT cells elicited a profound and dose-related inhibition of the responses of all cells tested to noxious cutaneous stimuli. Only four cells (16.7%) were found to be inhibited when baclofen (a selective GABAB receptor agonist) was applied iontophoretically. However, a strong and dose-dependent inhibition of the responses to cutaneous mechanical and thermal stimuli was obtained in all cells examined when baclofen was administered into the dorsal horn through a microdialysis fiber. The inhibitory effects were mainly on nociceptive inputs. 3. The inhibition of cellular activity by GABAA and GABAB agonists could be selectively antagonized by specific antagonists applied through a microdialysis fiber. 4. The excitatory responses evoked by pulsed release of glutamic acid (GLUT) were also inhibited in a dose-related manner by iontophoretic application of GABA and muscimol, but not by baclofen. A high dose of baclofen administered by microdialysis resulted in only a small decrease in GLUT-evoked excitatory responses. 5. Infusion of GABAA and GABAB antagonists into the dorsal horn by microdialysis caused an increase in both background activity and responses to cutaneous stimuli, suggesting that there is a tonic GABAergic inhibition of STT cells. 6. The inhibition of responses to mechanical and thermal stimulation of the cutaneous excitatory receptive field resulting from stimulation in PAG was significantly antagonized in most of the STT cells tested when the GABAA antagonist bicuculline was infused into the spinal dorsal horn through a microdialysis fiber. In contrast, the inhibition produced by PAG stimulation in most of the cells examined was not significantly antagonized by the GABAB antagonists phaclofen or 3-amino-propyl(diethoxymethyl)phophinic acid (CGP35348) administered into the spinal dorsal horn by microdialysis. 7. Our results support the contention that GABAergic mechanisms in the spinal dorsal horn normally exert a tonic modulation of nociceptive inputs through both GABAA and GABAB receptors. The evidence provided here indicates that GABAA receptors located on primate STT neurons contribute to a postsynaptic inhibitory effect on the transmission of peripheral nociceptive inputs. A possible presynaptic GABAA action was not investigated. Our finding of a GABAB-receptor-mediated inhibition is consistent with the view that both pre- and postsynaptic GABAB receptors are involved in inhibitory modulation of spinal nociceptive transmission. Finally, it is suggested from this study that primate spinal GABAA, but not GABAB receptors, are involved in mediating the descending inhibition induced by PAG stimulation.

Chapter 12 Cooperative mechanisms of neurotransmitter action in central nervous sensitization

This chapter focuses on the mechanisms of central sensitization of nociceptive pathways using two animal models—intradermal injection of capsaicin and induction of acute arthritis. It also explores the possibility of provoking sensitization more directly by administering drugs into the dorsal horn, either by iontophoresis or by microdialysis. Central sensitization is characterized in the experiments by the following—(1) changes in the responses of primate spinothalamic tract (STT) neurons to stimulation of the skin, including increased responses to innocuous and marginally noxious stimuli and an enlarged receptive field; (2) behavioral responses to stimulation of the skin in rats indicative of allodynia and/or hyperalgesia; (3) morphological alterations in the dorsal horn in rats and monkeys; and (4) release of neurotransmitters into the dorsal horn, as determined by microdialysis and high performance liquid chromatography (HPLC) in rats and monkeys. Evidence that sensitization of central neurons can occur for periods of up to a few hours without maintained peripheral input comes from both in vivo and in vitro experiments.

Effects of upper cervical spinal cord stimulation on neurons in the lumbosacral enlargement of the cat: spinothalamic tract neurons

Extracellular microelectrode recordings were made from deep spinothalamic tract neurons in the lumbosacral spinal cord of cats anaesthetized with chloralose and paralyzed with gallamine triethiodide. The effects of upper cervical spinal cord stimulation were tested on 43 spinothalamic tract neurons, by stimulation of the ipsilateral dorsolateral funiculus at C3 and rostral C1 using five or six shocks at 333 Hz. The strength of cervical stimulation was adjusted so that the C3 shock was above threshold for antidromic activation of spinocervical tract neurons but the same strength of shock applied at C1 was below threshold for the same neurons. Four of the 43 spinothalamic cells (9%) were not influenced by upper cervical stimulation. The remaining 39 spinothalamic tract cells (91%) were all excited from the upper cervical cord. Twenty-seven of these (63%) were excited more strongly from C3 than from C1, 4 (9%) were excited more strongly from C1 than from C3, and the remaining eight cells (19%) showed no significant differences between their responses to stimulation at C1 and C3. There were no obvious differences between those spinothalamic tract neurons showing differential effects from C1 and C3 and those showing no such effects. The neuronal systems possibly responsible for the differential effects from C3 and C1 on spinothalamic tract neurons are discussed. We conclude that the most likely candidate system for the greater excitation from C3 compared with C1 is the subset of spinocervical tract neurons with axon collaterals in the lumbosacral enlargement and that the spinothalamic tract is a further ascending path, in addition to the postsynaptic dorsal column path, that receives excitatory input from spinocervical axon collaterals. The greater excitation from C1 compared with C3 is interpreted as due to excitation from C1 and a mixture of excitation and inhibition from C3. The responsible neuronal systems seem likely to be either the spinocervical neurons with axon collaterals operating on the spinothalamic tract via inhibitory interneurons, or cells in the lateral cervical nucleus with axons descending to the lumbosacral cord.

NMDA R1 mRNA distribution in motor and thalamic-projecting sensory neurons in the rat spinal cord and brain stem

The N-methyl- D-aspartate (NMDA) receptor is important in both sensory and motor neurotransmission. In this study we examine NMDA R1 mRNA hybridization signal over individual sensory and motor neurons in the spinal cord and brain stem. A significantly greater quantity of NMDA RI mRNA was present in motor neurons of the lumbar spinal cord and hypoglossal nucleus compared to thalamic projecting sensory neurons in the spinal cord dorsal horn, the spinal trigeminal nucleus pars caudalis and the cuneate and gracile nuclei. No significant difference in the quantity of NMDA R1 mRNA was observed between sensory neurons known to relay predominantly nociceptive information (trigeminothalamic and spinothalamic tract neurons) and those that relay predominantly touch and proprioceptive information (dorsal column neurons).

Infusion of substance P or neurokinin A by microdialysis alters responses of primate spinothalamic tract neurons to cutaneous stimuli and to iontophoretically released excitatory amino acids

The responses of 25 spinothalamic tract (STT) neurons to mechanical and thermal stimulation of the skin, as well as to a battery of iontophoretically applied excitatory amino acids (EAAs), were tested before and then during microdialysis of substance P (SP) or neurokinin A (NKA) into the dorsal horn of anesthetized monkeys. Neither peptide had significant effects on the background activity or the responses to mechanical or thermal stimulation of the skin. However, each peptide produced significant increases in the responses to iontophoretic application of one or more EAAs. In addition, following combined application of the EAAs and either SP or NKA, the responses of the cells to mechanical stimulation of the skin increased. Combined application of SP and NKA failed to produce an increase in responses to either the EAAs or to cutaneous stimuli that was greater than that produced by either peptide alone. It is concluded that SP and NKA produce an increase in the responses of STT cells to iontophoretic applications of EAAs and the combined effects of these compounds produce sustained increases in responses to mechanical stimulation of the skin. These changes mimic those observed when STT cells are sensitized by peripheral noxious stimuli, suggesting that the mechanism of induction and expression of sensitization involves the facilitation of dorsal horn neuron responses to EAAs by tachykinins.

Evidence for glutamate as neurotransmitter in trigemino-and spinothalamic tract terminals in the nucleus submedius of cats.

The nucleus submedius in the medial thalamus of cats is an important termination site for lamina I trigemino-and spinothalamic tract (TSTT) neurons, many of which are nociceptive-specific, and the nucleus submedius has been proposed to be a dedicated nociceptive substrate involved in the affective aspect of pain. In the present study, the distribution of glutamate was examined by immunocytochemical methods in order to evaluate the possible role of this amino acid as a neurotransmitter in TSTT terminals in the nucleus submedius. TSTT terminals were identified by anterograde transport of horseradish peroxidase and wheatgerm agglutinin-horseradish peroxidase conjugate from the spinal cord or the medullary dorsal horn. Quantitative analysis of immunogold labelling revealed that TSTT terminals contain about twice the tissue average of glutamate-like immunoreactivity. A strong positive correlation was found between the density of synaptic vesicles and the density of gold particles in these terminals, whereas no relationship was seen between these variables in GABAergic presynaptic dendrites. Enrichment of glutamate-like immunoreactivity (approximately 250% of the tissue average) was also observed in terminals of presumed cortical origin. Presynaptic dendrites and neuron cell bodies in the nucleus submedius were found to contain relatively low levels of glutamate-like immunoreactivity, at or below the tissue average. These observations provide evidence that glutamate is a neurotransmitter in lamina I TSTT terminals in the nucleus submedius. The findings also suggest glutamatergic neurotransmission between cortical afferents and nucleus submedius neurons. Glutamate is therefore likely to be an important mediator of nociceptive processing in the medial thalamus.

Neurokinin 1 and 2 antagonists attenuate the responses and NK1 antagonists prevent the sensitization of primate spinothalamic tract neurons after intradermal capsaicin

1. Activation of neurokinin receptors contributes to the excitation of many dorsal horn neurons by cutaneous sensory stimuli, particularly noxious stimuli. In the present study we investigate the role of neurokinin receptors in the activation of primate spinothalamic tract (STT) neurons by cutaneous mechanical stimuli and by intradermal injection of capsaicin. This was done by testing the responses of these neurons to a battery of cutaneous stimuli before and during infusion by microdialysis of antagonists selective for NK1 and NK2 receptors. 2. The NK1 receptor antagonists cis-3-(2-methoxybenzyl-amino-2-benzhydrylquinuclidine (CP96345) and D-Pro9-[Spiro-y-lactam]-Leu10,Trp11)-Physalaemin(1-11) (GR82334) did not significantly reduce the responses of STT cells to mechanical stimulation of the skin. Both NK1 antagonists did, however, produce a significant reduction in the responses of STT neurons to an intradermal injection of capsaicin. Finally, despite having no effects on responses to mechanical stimuli, both NK1 antagonists prevented the sensitization of the responses to cutaneous stimuli that is usually observed after intradermal injections of capsaicin. 3. The NK2 selective antagonists PhCO-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (GR98400) and [Tyr5,D-Trp6,8,9,Lys10]-NKA (4-10) (MEN10376) had effects very similar to those of the NK1 antagonists, but with an important difference. Neither NK2 antagonist affected the responses of STT neurons to noxious or innocuous mechanical stimulation of the skin, but they did reduce the responses to intradermal capsaicin injections. These compounds failed to prevent capsaicin-induced sensitization. In fact, cells exposed to GR98400 or MEN10376 showed unusually sustained increases in the responses to mechanical stimuli after the first capsaicin injection, suggesting that these compounds actually induced sensitization. 4. These results support the contention that both neurokinin receptors participate in the processing of nociceptive information in the dorsal horn, especially responses to strong stimuli such as intradermal injection of capsaicin. NK1 receptors are also involved in the sensitization of STT neurons after peripheral injury. A clearer understanding of the role of NK2 receptors in sensitization requires further studies with improved antagonists.

The role of the spinothalamic tract in the plastic changes in somatosensory thalamus and cortex caused by inflammation

Dr. Guilbaud describes 15 years of work in her laboratory in which she and her colleagues examined plastic changes in the responses of neurons in the rat somatosensory thalamus and cerebral cortex following the induction of an inflammatory pain state, either by injection of Freund's adjuvant into the tail or of carrageenan into the hindpaw. The goals of this work included: a demonstration of changes in neural responses that parallel the development of hyperalgesia and allodynia in the inflamed area; a description of changes in response to stimulation of uninflamed areas that might help explain secondary hyperalgesia; investigation of the question of whether a specific joint pain system exists; and exploration of how altered joint input might dominate cortical responses atthe expense of other somatic inputs. I will elaborate on the first three of these from the perspective of experiments on primate spinothalamic tract neurons in my laboratory.

Glycine and GABA A antagonists reduce the inhibition of primate spinothalamic tract neurons produced by stimulation in periaqueductal gray

Amino acids are demonstrated to be important neurotransmitters mediating the inhibitory transmission from nucleus raphe magnus to spinal nociceptive dorsal horn neurons. In this study, the role of glycine and GABA in the inhibitory processes evoked by stimulation in periaqueductal gray (PAG) of responses of primate spinothalamic tract (STT) neurons to cutaneous mechanical and thermal stimuli was investigated by examining the effects of strychnine and bicuculline, antagonists of glycine and GABA A receptors, respectively, introduced into the dorsal horn through a microdialysis fiber. The inhibitory effects of iontophoretic application of glycine and GABA A agonists on STT cell activity evoked by noxious mechanical stimulation of the skin were selectively blocked by their specific antagonist, strychnine or bicuculline, infused into the dorsal horn. Similarly, intra-spinal application of strychnine or bicuculline resulted in a significant reduction in the PAG stimulation-induced inhibition of responses of STT cells to cutaneous stimuli. This reduction was mainly on the PAG-induced inhibition of the responses to noxious mechanical stimuli. Our results suggest that glycinergic and GABAergic inhibitory interneurons in the spinal cord dorsal horn synapsing on STT cells are activated during stimulation in PAG and contribute to descending antinociceptive actions.

The Thermal Grill Illusion: Unmasking the Burn of Cold Pain

In Thunberg's thermal grill illusion, first demonstrated in 1896, a sensation of strong, often painful heat is elicited by touching interlaced warm and cool bars to the skin. Neurophysiological recordings from two classes of ascending spinothalamic tract neurons that are sensitive to innocuous or noxious cold showed differential responses to the grill. On the basis of these results, a simple model of central disinhibition, or unmasking, predicted a quantitative correspondence between grill-evoked pain and cold-evoked pain, which was verified psychophysically. This integration of pain and temperature can explain the thermal grill illusion and the burning sensation of cold pain and may also provide a basis for the cold-evoked, burning pain of the classic thalamic pain syndrome.

Medial lemniscal and spinal projections to the macaque thalamus: an electron microscopic study of differing GABAergic circuitry serving thalamic somatosensory mechanisms

The synaptic relationships formed by medial lemniscal (ML) or spinothalamic tract (STT) axon terminals with neurons of the somatosensory ventroposterolateral thalamic nucleus of the macaque monkey have been examined quantitatively by electron microscopy. ML and STT axons were labeled by the anterograde axon transport of WGA-HRP following injection of the tracer into the contralateral dorsal column nuclei, or the dorsal horn of the spinal cord, respectively. Thalamic tissue was histochemically reacted for the presence of HRP. Serial thin sections were stained with a gold-labeled antibody to GABA, to determine which neuronal elements exhibited GABA immunoreactivity (GABA-ir). Serially sectioned thalamic structures were recorded in electron micrographs and reconstructed in three dimensions by computer. Individual ML axon terminals form multiple synaptic contacts with segments of the proximal dendritic trees of thalamocortical relay neurons and also synapse upon the dendritic appendages of GABA-ir interneurons (local circuit neurons). These GABA-ir dendritic appendages contain synaptic vesicles and are presynaptic (presynaptic dendrites) to the same segments of relay neuron dendrites that receive ML contacts. When analyzed in serial sections and reconstructed by computer, the ML terminals form triadic relationships (ML, GABA appendage, and relay neuron dendrite) or more complex glomerular arrangements involving multiple appendages, all of which then contact the relay neuron dendritic segment. In contrast, multiple STT terminals make synaptic contacts along segments of projection neuron dendrites and are usually the only type of profile to contact that segment of dendrite. More than 85% of the spinal afferents form simple axodendritic synapses with relay cells and do not contact GABA-ir appendages. The thalamic synaptic relationships of ML terminals are fundamentally different from those formed by the STT. Because STT neurons predominatly transmit information about noxious stimuli, the simple axodendritic circuitry of the majority of these spinal afferents suggests that the transmission of noxious information is probably not subject to GABAergic modulation by thalamic interneurons, in contrast to the GABAergic processing of non-noxious information carried by the ML afferents. The differences in the GABAergic circuits of the thalamus that mediate ML and STT afferent information are believed to underlie differential somatosensory processing in the forebrain. We suggest that changes in thalamic GABAergic dendritic appendages and GABA receptors following CNS injury may play a role in the genesis of some central pain states.

Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. II. Responses to innocuous and noxious mechanical and thermal stimuli.

1. The goal of this study was to gather data that would increase our understanding of nociceptive processing by spinothalamic tract (STT) neurons that receive inputs from the hand and arm. Fifty neurons in the cervical enlargement of urethan-anesthetized rats were antidromically activated from the contralateral posterior thalamus. A stimulating electrode was moved systematically within an anterior-posterior plane in the thalamus until a point was located where the smallest amount of current antidromically activated the neuron. The antidromic thresholds at each of these lowest threshold points was < or = 30 microA; the mean antidromic threshold was 15.4 +/- 1.0 (SE) microA. Lowest threshold points were found primarily in the posterior thalamic group (Po), zona incerta, and in or near the supraoptic decussation. 2. The recording sites of 47 neurons were marked and recovered. Recording sites were located in the superficial dorsal horn (SDH, n = 15), deep dorsal horn (DDH, n = 31), and ventral horn (n = 1). Recording sites were located across the mediolateral extent of the SDH. Within the DDH, recording sites were concentrated laterally in nucleus proprius and dorsally in the lateral reticulated area. The locations of the recording points confirm previous anatomic descriptions of STT neurons in the cervical enlargement. 3. Cutaneous excitatory receptive fields were restricted to the ipsilateral forepaw or forelimb in 67% (10/15) of the neurons recorded in the SDH and 42% (13/31) of the neurons recorded in the DDH. Neurons having larger, more complex receptive fields were also commonly encountered. Thirty-three percent (5/15) of the neurons recorded in the SDH and 58% (18/31) recorded in the DDH had receptive fields that were often discontinuous and included areas of the ipsilateral shoulder, thorax, and head, including the face. 4. Innocuous and noxious mechanical stimuli were applied to the receptive field of each neuron. Fifty percent (25/50) responded to innocuous mechanical stimuli but responded at higher frequencies to noxious stimuli (wide dynamic range, WDR). Forty-four percent (22/50) responded only to noxious stimuli (high threshold, HT). Six percent (3/50) responded preferentially to innocuous stimuli (low threshold, LT). WDR and HT neurons were recorded in both the SDH and DDH, including nucleus proprius, an area not typically associated with nociceptive transmission at other levels of the cord. Sixty percent (9/15) of the units recorded in the SDH were classified as WDR neurons; the other 40% (6/15) were classified HT. Forty-eight percent (15/31) of the units recorded in the DDH were classified as WDR neurons and 42% (13/31) as HT.(ABSTRACT TRUNCATED AT 400 WORDS)

Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. I. Locations of antidromically identified axons in the thalamus and hypothalamus

1. Seventy-seven neurons in the cervical enlargement of rats anesthetized with urethan were initially antidromically activated using currents < or = 30 microA from the contralateral posterior thalamus. A goal of these experiments was to determine the course of physiologically characterized spinal axons within the diencephalon. Therefore, in 38 cases, additional antidromic mapping was done throughout the mediolateral extent of the diencephalon at multiple anterior-posterior planes. 2. Electrolytic lesions marking the recording sites were recovered for 71 neurons. Thirty-one were located in the superficial dorsal horn (SDH); 39 were in nucleus proprius or the lateral reticulated area of the deep dorsal horn (DDH), and one was in the ventral horn. 3. Eight of 38 (21%) neurons that were tested for more anterior projections could only be antidromically activated with currents < or = 30 microA from sites in the contralateral posterior thalamus. Such neurons are referred to as spinothalamic tract (STT) neurons. Lesions marking the lowest threshold points for antidromic activation were located in or near the posterior thalamic group (Po). At more anterior levels, considerably higher currents were required for antidromic activation or it was not possible to activate the neurons with currents up to 500 microA. Four of these neurons were physiologically characterized and each responded preferentially to noxious mechanical stimuli (wide dynamic range, WDR). Each of the three neurons that were tested responded to noxious heat stimuli. These findings confirm anatomic studies that have shown that a number of STT axons terminate in Po and suggest that such axons that originate in the cervical enlargement carry nociceptive input from the upper extremity. 4. In 15 cases, electrode penetrations were made systematically throughout much of the contralateral ventrobasal complex (VbC). In 17 cases, penetrations were made throughout the intralaminar nuclei contralaterally, including the central lateral nucleus (CL). Surprisingly, only one of the examined axons was antidromically activated with low currents from CL and one from VbC, although both of these nuclei are known to receive sizeable inputs from the STT. 5. Many of the axons (27 of the 38 tested, 71%) that were initially antidromically activated from the contralateral posterior thalamus could also be antidromically activated with low currents (< or = 30 microA) and at increased latencies from sites located anteriorly in the contralateral hypothalamus. Such neurons are referred to as spinothalamic tract/spinohypothalamic tract (STT/SHT) neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of trans-ACPD, a metabotropic excitatory amino acid receptor agonist, on the responses of primate spinothalamic tract neurons

The responses of primate spinothalamic tract (STT) neurons to innocuous and noxious mechanical stimuli applied to the skin can be enhanced for more than an hour following prolonged noxious stimulation. This increased responsiveness is thought to reflect sensitization of dorsal horn neurons and may help account for secondary hyperalgesia and mechanical allodynia. The proposal that central sensitization is due to the activation of second messenger systems was tested in this study by examining the effect of trans-ACPD ( trans- d,l-1-amino-1, 3-cyclopentanedicarboxylic acid), an agonist of metabotropic excitatory amino acid (EAA) receptors, introduced into the dorsal horn by microdialysis. A low dose of trans-ACPD resulted in an increase in the responses of STT cells to an innocuous mechanical stimulus (BRUSH), but no increase in the responses to noxious mechanical and thermal stimuli or in the excitation produced by iontophoretically applied EAAs. A high dose of trans-ACPD caused a transient increase in background activity, but no change in the responsiveness of spinothalamic cells to any of the test stimuli. It is concluded that low doses of trans-ACPD can selectively enhance transmission through interneuronal pathways mediating tactile inputs to spinothalamic cells.

Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. III. Locations of antidromically identified axons in the cervical cord white matter

1. Fifty-five neurons in the cervical enlargement (C6-C8) of urethan-anesthetized rats were antidromically activated from the contralateral posterior diencephalon. In all cases, antidromic thresholds were < or = 30 microA. The locations of the axons of these neurons within the white matter of segments C2-C6 were determined by tracking systematically using a second antidromic stimulating electrode. 2. The recording locations of 51 neurons were marked and recovered. Twenty neurons were recorded in the superficial dorsal horn (SDH) and 31 were in the deep dorsal horn (DDH). Eighty-three lowest threshold points for antidromic activation within the white matter of segments C2-C6 were determined for these 51 neurons. The mean antidromic threshold at these points was 9.5 +/- 0.5 (SE) microA. For 26 neurons, the lowest threshold point for antidromic activation was determined at one segmental level. We also attempted to determine whether individual axons maintained their position as they ascended through the cervical cord white matter. In 25 cases, lowest threshold points were determined at two or more segmental levels. 3. In segments C5-C6, 88% (7/8) of the lowest threshold points of the examined axons were located in the contralateral ventral funiculus, indicating that the majority of examined axons crossed the midline within one or two segments. 4. In segments C3-C4, 32% (14/44) of all examined axons were found in the dorsal lateral funiculus (DLF) and 66% (29/44) were within the ventral quadrant [ventral lateral funiculus (VLF) and ventral funiculus (VF)]. Sixty-nine percent (11/16) of the axons of neurons recorded in the SDH were located in the contralateral DLF and 31% (5/16) were located in the ventral quadrant (VQ). In contrast, only 11% (3/28) of the axons of neurons recorded in the DDH were located in the contralateral DLF and 86% (24/28) were located in the VQ. Therefore, in segments C3-C4, the locations of axons differed significantly. Those from neurons recorded in the SDH were located primarily in the DLF and those from neurons recorded in the DDH were located principally in the VQ. 5. In segment C2, 74% (23/31) of all examined axons were found in the DLF, 23% (7/31) were in the VQ, and 3% (1/31) were in the dorsal horn. Thus, the percentage of all examined axons in the DLF in C2 was approximately 2.5 times greater than it was in C3-C4.(ABSTRACT TRUNCATED AT 400 WORDS)

Neurogenesis of spinothalamic and spinocerebellar tract neurons in the lumbar spinal cord of the rat

The temporal and spatial neurogenic patterns of spinothalamic and spinocerebellar neurons were determined in spinal cord segment L1 of the rat. Neurogenic patterns were demonstrated with [ 3H]thymidine administered to fetal rats during the period when neurons with supraspinal projections are known to be generated, i.e. on one of embryonic (E) days E13, E14, or E15. The animals were allowed to survive 50 to 100 days postpartum, then neurons with spinothalamic and spinocerebellar projections were retrogradely filled with fluorescent axonal tracers, Fluoro-Gold or True blue, which were pressure injected into the dorsal thalamus and cerebellum in various combinations in the same and in separate animals. Neurons labeled with each retrograde tracer and [ 3H]thymidine and neurons labeled with retrograde tracers alone were counted in spinal cord segment L1 in each of the animals. Spinothalamic and spinocerebellar neurons were found to be separate and distinct populations. Statistical analysis of the data showed that spinothalamic and spinocerebellar neurons also have distinctly different patterns of neurogenesis which suggest early determination in each cell line. The temporal neurogenic pattern followed a projection-distance gradient, such that spinothalamic neurons, which have longer axons than spinocerebellar neurons, completed neurogenesis prior to spinocerebellar neurons in each region of the spinal gray.

Effects of systemic morphine on lamina I spinothalamic tract neurons in the cat

Lamina I spinothalamic tract (STT) neurons are an integral component of the central representation of pain and temperature and thus their sensitivity to various analgesics needs to be examined. In the present study, the effects of successive, cumulative doses (0.125–2.0 mg/kg) of intravenous morphine sulfate on the quantitative stimulus-response properties of nociceptive lamina I STT cells have been tested in the intact, barbiturate-anesthetized cat. Both nociceptive-specific ( n = 7) and multireceptive (heat, pinch and cold sensitive; n = 7) lamina I STT cells were inhibited in a dose-dependent manner. Parallel dose-dependent effects on responses to noxious heat and pinch were generally observed that reduced ongoing discharge levels and the slopes of the stimulus-response functions. However, non-STT lamina I cells ( n = 5) differed significantly; the responses of one multireceptive (heat, pinch and cold-sensitive) cell and the responses to pinch of 3 of 4 wide dynamic range cells were not inhibited. In addition, two-thirds of the nociceptive lamina I STT cells showed enhanced responses at the lowest dose of morphine (0.125 mg/kg). These results contrast with the varied effects of morphine reported for superficial dorsal horn cells with uncharacterized projections and they support the role of lamina I STT cells in pain. Furthermore, these observations are consistent with previous findings indicating that lamina I STT neurons are a distinct subpopulation of lamina I cells. These results support previous evidence that opiatergic modulation of sensory activity in lamina I is functionally organized.