Spinothalamic Tract Terminals Research Articles

Alterations of Contralateral Thalamic Perfusion in Neuropathic Pain

Contralateral thalamus, the place of termination of spinothalamic tract, is affected in patients with pain. We employed single photon emission computed tomography (SPECT) to evaluate the thalamic perfusion in patients with spontaneous neuropathic pain. Ten patients with complex regional pain syndrome (CRPS) and eleven radiculopathiy patients were enrolled in this study. Regional cerebral blood flow of thalamus was assessed bilaterally by iodine-123-labelled iodoamphetamine SPECT. To standardize the inter-patient data, we set a contralateral thalamic uptake index (CTUI) for assessing thalamic asymmetry. In one study, we found elevation of CTUI in patients with symptoms of neuropathic pain for less than 12 month, whereas no change was observed in the case of a longer lasting disease. An another study demonstrated decrease of CTUI after pain treatment, even though it was unrelated to the pain intensity prior to treatment. Our SPECT study revealed that neuropathic pain altered thalamic neuronal activity. CTUIs were increased in early stage of the disease but decreased as the disease progressed to the chronic stage. These results suggest that CTUI can be used to improve management of neuropathic pain for proper evaluation of spontaneous pain.

GABA-like immunoreactivity in the thalamic nucleus submedius of the cat.

The distribution of GABAergic elements and their synaptic contacts in the nucleus submedius, a specific nociceptive relay in the medial thalamus of the cat, was studied using light and electron-microscopic postembedding immunohistochemical methods. About one-fourth of the neurons in nucleus submedius were GABA immunoreactive. These neurons were generally smaller than the unlabeled neurons and are probably local circuit neurons. Electron microscopy showed GABA immunoreactivity in two types of vesicle-containing profiles, F-terminals and presynaptic dendrites. F-terminals formed simple synapses with the dendrites of presumed thalamocortical relay cells. Presynaptic dendrites were involved in more complex synaptic arrangements that included ascending trigeminothalamic and spinothalamic tract terminals and thalamocortical relay cell dendrites. Analysis of single sections showed that about 40% of the trigeminothalamic and spinothalamic tract terminals, identified by anterograde transport of horseradish peroxidase, were presynaptic to GABAergic presynaptic dendrites. These results show that GABAergic neurons are frequent in nucleus submedius and that the GABAergic elements make synaptic connections similar to those described for other sensory relay nuclei, including the somatosensory ventroposterior nucleus. This suggests that GABAergic mechanisms play an important role in the processing of nociceptive and thermoreceptive information.

Evidence for glutamate as a neurotransmitter in spinothalamic tract terminals in the posterior region of owl monkeys

Previous studies have suggested that glutamate is a neurotransmitter in ascending somatosensory pathways to the thalamus. The present study examined with quantitative immunohistochemical methods the presence of glutamate in spinothalamic tract terminals of owl monkeys (Aotus trivirgatus). Such terminals in the posterior region, in which a nucleus was recently identified as a specific pain and temperature relay in macaques and humans, were labeled by anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase, injected into the spinal dorsal horn. Glutamate-like immunoreactivity was demonstrated with a postembedding immunogold procedure using a well-characterized glutamate antiserum. Quantitative analysis of the immunogold labeling demonstrated that the spinothalamic tract terminals contained more than twice the tissue average of glutamate-like immunoreactivity. Enrichment of glutamate-like immunoreactivity was also found in terminals of presumed cortical origin. Presynaptic dendrites, cell bodies and non-vesicle-containing dendrites displayed low levels of glutamate-like immunoreactivity. A strong positive correlation (r = 0.69; P < 0.0001) was found between the density of synaptic vesicles and the density of gold particles in spinothalamic tract terminals, in contrast to a weak negative relationship (r = -0.28; P = 0.089) present in GABAergic presynaptic dendrites. These data provide strong evidence that the gold labeling in the spinothalamic tract terminals represents transmitter labeling, implying that glutamate is a neurotransmitter for ascending nociceptive and thermoreceptive information in primates.

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.

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.

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.

The spinothalamic tract in the primate: A re-examination using wheatgerm agglutinin conjugated to horseradish peroxidase

The sites of termination of the primate spinothalamic tract have been reinvestigated using the anterograde transport of wheatgerm agglutinin conjugated to horseradish peroxidase. Monkeys which received an injection of the conjugate at the spinal cervical level (C7–C8) displayed a “patchy” pattern of labelling in the coronal plane in the ventral posterior lateral and caudal ventrolateral nucleus. In three dimensional reconstructions this labelling appeared to be rod-like in shape. A more homogeneous pattern of labelling was present in parts of the central lateral, posterior, suprageniculate, limitans, submedius, medial dorsal, paracentral, central medial, reuniens and periventricular nucleus. Lumbar injections (L2–L3) produced a similar although less intense pattern of labelling with only the ventral posterior lateral and ventrolateral nuclei displaying an obvious topological organization. Comparison of these results with previous physiological and pharmacological reports suggests several morphological-functional correlations: first, that both the discriminative and motivational/arousal aspects of spinothalamic tract function, associated with the lateral and medial thalamic nuclei, respectively, may be conveyed by direct spinothalamic tract projections. In support of this hypothesis medial spinothalamic tract termination sites receive a homogeneous input which does not have an obvious topographical organization, whereas lateral spinothalamic tract termination sites receive a “patchy” pattern of terminals which are topographically organized; second, that the patchy pattern of labelling observed in the coronal plane in the lateral thalamus corresponds to a “rodlike” pattern of labelling in three dimensions. This “rodlike” pattern of labelling has previously been observed for medial lemniscal projections to the thalamus and has been postulated to be the thalamic equivalent of cortical “columns”; third, that there appears to be a tight overlap between spinothalamic tract terminals and opiate receptor binding in some medial but not lateral thalamic nuclei. Such an overlap may be indicative of a pharmacological difference in the types of spinothalamic tract inputs which could be modulated by opiates at the thalamic level.