The functional anatomy of lamina I and its role in post-stroke central pain.
Explore the source record for details and available documents.
Afferent Pathways↗
Biomedical subjects
A D Craig
Publications and source records attributed to A D Craig.
Thermosensory activation of insular cortex.
Temperature sensation is regarded as a submodality of touch, but evidence suggests involvement of insular cortex rather than parietal somatosensory cortices. Using positron emission tomography (PET), we found contralateral activity correlated with graded cooling stimuli only in the dorsal margin of the middle/posterior insula in humans. This corresponds to the thermoreceptive- and nociceptive-specific lamina I spinothalamocortical pathway in monkeys, and can be considered an enteroceptive area within limbic sensory cortex. Because lesions at this site can produce the post-stroke central pain syndrome, this finding supports the proposal that central pain results from loss of the normal inhibition of pain by cold. Notably, perceived thermal intensity was well correlated with activation in the right (ipsilateral) anterior insular and orbitofrontal cortices.
Adult↗
Cytoarchitectonic and immunohistochemical characterization of a specific pain and temperature relay, the posterior portion of the ventral medial nucleus, in the human thalamus.
Previous studies in the macaque monkey have identified a thalamic nucleus, the posterior portion of the ventral medial nucleus (VMpo), as a dedicated lamina I spinothalamocortical relay for pain and temperature sensation. The dense plexus of calbindin-immunoreactive fibres that characterizes VMpo in primates enables its homologue to be identified in the human thalamus by immunohistochemical labelling for calbindin. We have now analysed in detail the cytoarchitectonic characteristics of VMpo and its relationship with immunoreactivity for calbindin, substance P and calcitonin gene-related peptide (CGRP) in the human thalamus. The area in the posterolateral thalamus in which dense calbindin-immunoreactive fibre terminations are present coincides nearly completely with a distinct region that contains small to medium-sized cells with round or oval shapes that are aggregated in clusters separated by cell sparse areas. This region, which we identify as VMpo, is located posteromedial to the ventral posterior lateral (VPL) and ventral posterior medial (VPM) nuclei, ventral to the anterior pulvinar and centre médian nuclei, lateral to the limitans and parafascicular nuclei and dorsal to the medial geniculate nucleus. Calbindin-immunoreactive fibres enter VMpo from the spinal lemniscus and form large patches of dense terminal-like staining over clusters of VMpo neurons. A few of these clusters also display terminal-like substance P labelling. Small bursts of CGRP staining are intercalated between the calbindin-labelled clusters, but there is little or no overlap between these two markers. CGRP immunoreactivity is also present over small, non-clustered neurons in the calbindin-negative area that separates VMpo from the VPL and VPM nuclei, which we denote as the posterior nucleus (Po). These observations provide a concise description of VMpo in the human thalamus. Further, they suggest that the lamina I spinothalamic tract fibres (represented by calbindin and probably also substance P immunoreactivity) and vagal-solitary-parabrachial afferents (represented by CGRP immunoreactivity) form closely related, but separate, termination fields that can be considered to represent different aspects of enteroceptive information regarding the physiological status of the tissues and organs of the body. The location of VMpo and the adjacent Po fits with clinical descriptions of the thalamic area from which pain, temperature and visceral sensations can be evoked by microstimulation, and where nociceptive and thermoreceptive neurons have been recorded in humans. It also corresponds to the area in which infarcts cause analgesia and thermoanaesthesia and can lead to the paradoxical development of central pain.
Afferent Pathways↗
NK-1 receptor immunoreactivity in distinct morphological types of lamina I neurons of the primate spinal cord.
In cat and monkey, lamina I cells can be classified into three basic morphological types (fusiform, pyramidal, and multipolar), and recent intracellular labeling evidence in the cat indicates that fusiform and multipolar lamina I cells are two different types of nociceptive cells, whereas pyramidal cells are innocuous thermoreceptive-specific. Because earlier observations indicated that only nociceptive dorsal horn neurons respond to substance P (SP), we examined which morphological types of lamina I neurons express receptors for SP (NK-1r). We categorized NK-1r-immunoreactive (IR) lamina I neurons in serial horizontal sections from the cervical and lumbar enlargements of four monkeys. Consistent results were obtained by two independent teams of observers. Nearly all NK-1r-IR cells were fusiform (42%) or multipolar (43%), but only 6% were pyramidal (with 9% unclassified). We obtained similar findings in three monkeys in which we used double-labeling immunocytochemistry to identify NK-1r-IR and spinothalamic lamina I neurons retrogradely labeled with cholera toxin subunit b from the thalamus; most NK-1r-IR lamina I spinothalamic neurons were fusiform (48%) or multipolar (33%), and only 10% were pyramidal. In contrast, most (approximately 75%) pyramidal and some (approximately 25%) fusiform and multipolar lamina I spinothalamic neurons did not display NK-1r immunoreactivity. These data indicate that most fusiform and multipolar lamina I neurons in the monkey can express NK-1r, consistent with the idea that both types are nociceptive, whereas only a small proportion of lamina I pyramidal cells express this receptor, consistent with the previous finding that they are non-nociceptive. However, these findings also indicate that not all nociceptive lamina I neurons express receptors for SP.
Animals↗
A distinct thermoreceptive subregion of lamina I in nucleus caudalis of the owl monkey.
An immunohistochemically distinct zone was identified in the superficial aspect of trigeminal nucleus caudalis of the New World owl monkey that is not immunoreactive for substance P or serotonin, in stark contrast to the dense staining present in the surrounding laminae I and II. Thionin-stained sections in different planes showed that this is a subregion of lamina I containing clusters of neurons that appear to have pyramidal or polygonal somata. Extracellular microelectrode recordings in this region revealed clusters of thermoreceptive-specific (COLD) cells with nasal or labial receptive fields, whereas nociceptive neurons were found in the adjacent portions of lamina I. Anterograde tracer injections in this region produced trigeminothalamic terminal labeling in the site homologous to the lamina I spino-thalamo-cortical relay nucleus identified previously in the Old World macaque monkey and in humans. Retrograde tracer injections involving this thalamic site, where recordings of trigeminal COLD-like neurons were obtained, produced clusters of retrogradely labeled trigeminothalamic neurons in this immunohistochemically distinct subregion of lamina I, nearly all of which are pyramidal neurons. We conclude that the nocturnal owl monkey has a specialized perinasal thermoreceptive trigeminothalamic sensory pathway that is probably of behavioral significance during olfactory sniffing. In addition, these observations corroborate other findings that have indicated that lamina I COLD cells are pyramidal neurons and are not physiologically modulated by substance P or serotonin, in contrast to nociceptive neurons.
Afferent Pathways↗
Behavioral thermosensitivity after lesions of thalamic target areas of a thermosensory spinothalamic pathway in the cat.
The ability of 17 cats to discriminate floor temperatures 2-4 degrees C below the ambient temperature was tested before and after unilateral electrolytic thalamic lesions. The lesions were made contralateral to the paws showing better performance in the temperature discrimination task. They were aimed at one or more of the three main target areas of thermoreceptive-specific lamina I spinothalamic neurons [i.e., the nucleus submedius, the dorsomedial aspect of the ventral posterior medial nucleus, and the ventral aspect of the basal ventral medial nucleus (vVMb)], following microelectrode mapping of somatosensory thalamus. The thermosensory consequences of each lesion were measured in postoperative testing, beginning 6-8 days after the final preoperative test session. A mild but definite thermosensory deficiency was found in five cats, in which the response behavior on the contralateral side was reduced below the 69% criterion level for several sessions. Histological analysis indicated that these cats differed only by the inclusion in the lesion of all or part of vVMb. Consequently this area appears to be important for cats' thermosensory behavior. Nevertheless even large lesions of virtually all of the thermoreceptive lamina I spinothalamic projection areas produced only this mild thermosensory deficit in stark contrast with the massive defect observed previously after spinal lesions of the middle of the lateral funiculus, where lamina I axons ascend. Accordingly such spinal lesions were added at the C(4) level, on the same side as the thalamic lesions, in six cats 3 mo after the thalamic surgery. These lesions caused severe contralateral defects (i.e., chance level performance). Thus the present findings are taken to indicate that contralateral ascending projections to vVMb in the thalamus participate in cats' thermosensory discrimination but that ascending projections to the brain stem must play an important role in their behavioral thermosensitivity.
Animals↗
Nociceptive and thermoreceptive lamina I neurons are anatomically distinct.
Pain and temperature stimuli activate neurons of lamina I within the dorsal horn of the spinal cord, and although these neurons can be classified into three basic morphological types and three major physiological classes, earlier studies did not establish a structure/function correlation between their morphology and their physiological responses. We recorded and intracellularly labeled 38 cat lamina I neurons. All 12 fusiform cells were nociceptive-specific, responsive only to pinch and/or heat. All 11 pyramidal cells were thermoreceptive-specific, responsive only to innocuous cooling. Of ten multipolar cells, six were polymodal, responsive to heat, pinch and cold, and four were nociceptive-specific. Five unclassified cells had features consistent with this pattern. These results support the view that central pain and temperature pathways contain anatomically discrete sets of modality-selective neurons.
Animals↗
Control of size and excitability of mechanosensory receptive fields in dorsal column nuclei by homolateral dorsal horn neurons.
Both accidental and experimental lesions of the spinal cord suggest that neuronal processes occurring in the spinal cord modify the relay of information through the dorsal column-lemniscal pathway. How such interactions might occur has not been adequately explained. To address this issue, the receptive fields of mechanosensory neurons of the dorsal column nuclei were studied before and after manipulation of the spinal dorsal horn. After either a cervical or lumbar laminectomy and exposure of the dorsal column nuclei in anesthetized cats, the representation of the hindlimb or of the forelimb was defined by multiunit recordings in both the dorsal column nuclei and in the ipsilateral spinal cord. Next, a single cell was isolated in the dorsal column nuclei, and its receptive field carefully defined. Each cell could be activated by light mechanical stimuli from a well-defined cutaneous receptive field. Generally the adequate stimulus was movement of a few hairs or rapid skin indentation. Subsequently a pipette containing either lidocaine or cobalt chloride was lowered into the ipsilateral dorsal horn at the site in the somatosensory representation in the spinal cord corresponding to the receptive field of the neuron isolated in the dorsal column nuclei. Injection of several hundred nanoliters of either lidocaine or cobalt chloride into the dorsal horn produced an enlargement of the receptive field of the neuron being studied in the dorsal column nuclei. The experiment was repeated 16 times, and receptive field enlargements of 147-563% were observed in 15 cases. These data suggest that the dorsal horn exerts a tonic inhibitory control on the mechanosensory signals relayed through the dorsal column-lemniscal pathway. Because published data from other laboratories have shown that receptive field size is controlled by signals arising from the skin, we infer that the control of neuronal excitability, receptive field size and location for lemniscal neurons is determined by tonic afferent activity that is relayed through a synapse in the dorsal horn. This influence of dorsal horn neurons on the relay of mechanosensory information through the lemniscal pathways must modify our traditional views concerning the relative independence of these two systems.
Animals↗
Morphology and distribution of spinothalamic lamina I neurons in the monkey.
Lamina I spinothalamic tract (STT) neurons were identified by retrograde labeling with cholera toxin subunit b (CTb) in monkeys. On the basis of the criteria of somatal shape and dendritic orientation in horizontal sections used in prior work in the cat, three distinct morphological types were recognized: fusiform (F) cells with spindle-shaped somata and two main longitudinal dendritic arbors; pyramidal (P) cells with triangular somata and three main dendrites oriented primarily longitudinally; and multipolar (M) cells with polygonal somata and four or more dendrites directed longitudinally and mediolaterally. Some cells had transitional shapes, but cells with indeterminate shapes and a few with small round, unipolar, or eccentric somata were grouped as unclassified (U). Greater variation appeared in the monkey than had been seen in the cat, and more subtypes were noted. The overall proportions of these cell types were: 47% F, 27% P, 22% M, and 5% U. Differential longitudinal distributions were found over the length of the spinal cord (from the second cervical through the first coccygeal segments). Pyramidal and multipolar cells together predominated in the enlargements, whereas fusiform cells predominated in thoracic segments. We conclude that three distinct morphological types of lamina I STT cells are present in the monkey as in the cat. Considered with other recent findings, the present results support the possibility that these three cell types may correspond to distinct physiological classes of nociceptive and thermoreceptive lamina I STT cells.
Animals↗
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.
Animals↗
Functional imaging of an illusion of pain.
Touching warm and cool bars that are spatially interlaced produces a painful burning sensation resembling that caused by intense, noxious cold. We demonstrated previously that this thermal grill illusion can be explained as an unmasking phenomenon that reveals the central inhibition of pain by thermosensory integration. In order to localize this unmasking in the human brain, we have used positron emission tomography (PET) to compare the cortical activation patterns evoked by the thermal grill and by cool, warm, noxious cold and noxious heat stimuli. The thermal grill illusion produces activation in the anterior cingulate cortex, whereas its component warm and cool stimuli do not. This area is also activated by noxious heat or cold. Thus, increased activity in the anterior cingulate cortex appears to be selectively associated with the perception of thermal pain. Disruption of thermosensory and pain integration may account for the central pain syndrome that can occur after stroke damage.
Adult↗
Fine structural organization of spinothalamic and trigeminothalamic lamina I terminations in the nucleus submedius of the cat.
We examined lamina I trigemino- and spinothalamic tract (TSTT) terminals labeled with Phaseolus vulgaris leucoagglutinin in the nucleus submedius (Sm), a nociceptive relay in the cat's thalamus. Volume-rendered (three-dimensional) reconstructions of ten lamina I TSTT terminals identified with light and electron microscopy were built from serial ultrathin sections by computer, which enabled the overall structures of the terminal complexes to be characterized in detail. Two fundamentally different terminations were observed: compact clusters of numerous boutons, which predominate in the dense focus of a lamina I terminal field in the Sm, and boutons-of-passage, which are present throughout the terminal field and predominate in its periphery. Reconstructions of cluster terminations reveal that all boutons of each cluster make synaptic contact with protrusions and branch points on a single dendrite and involve presynaptic dendrites (PSDs) in triadic arrangements, providing a basis for the secure relay of sensory information. In contrast, reconstructions show that boutons-of-passage are generally characterized by simple contacts with PSDs, indicating an ascending inhibitory lamina I influence. These different synaptic arrangements are consistent with physiological evidence indicating that the morphologically distinct nociceptive-specific and thermoreceptive-(cold)-specific lamina I TSTT neurons terminate differently within the Sm. Thus, a suitable structural substrate exists in the cat's Sm for the inhibitory effect of cold on nociception, a behavioral and physiological phenomenon of fundamental significance. We conclude that the Sm is more than a simple relay for nociception, and that it may be an integrative comparator of ascending modality-selective information that arrives from neurons in lamina I.
Animals↗
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.
Amidines↗
Association of spinal lamina I projections with brainstem catecholamine neurons in the monkey.
In addition to giving primary projections to the parabrachial and periaqueductal gray regions, ascending lamina I projections course through and terminate in brainstem regions known to contain catecholaminergic cells. For this reason, double-labeling experiments were designed for analysis with light and electron microscopy. The lamina I projections in the Cynomolgus monkey were anterogradely labeled with Phaseolus vulgaris leucoagglutinin (PHA-L) and catecholamine-containing neurons were labeled immunocytochemically for tyrosine hydroxylase (TH). Light level double-labeling experiments revealed that the terminations of the lamina I ascending projections through the medulla and pons strongly overlap with the localization of catecholamine cells in: the entire rostrocaudal extent of the ventrolateral medulla (A1 caudally, C1 rostrally); the solitary nucleus and the dorsomedial medullary reticular formation (A2 caudally, C2 rostrally); the ventrolateral pons (A5); the locus coeruleus (A6); and the subcoerulear region, the Kölliker-Fuse nucleus, and the medial and lateral parabrachial nuclei (A7). At the light microscopic level, close appositions between PHA-L-labeled lamina I terminal varicosities and TH-positive dendrites and somata were observed, particularly in the A1, A5 and the A7 cell groups on the contralateral side. At the electron microscopic level, examples of lamina I terminals were found synapsing on cells of the ventrolateral catecholamine cell groups in preliminary studies. The afferent input relayed by these lamina I projections could provide information about pain, temperature, and metabolic state as described previously. Lamina I input could impact interactions of the catecholamine system with higher brain centers modulating complex autonomic, endocrine, sensory, motor, limbic and cortical functions such as memory and learning. Nociceptive lamina I input to catecholamine cell regions with projections back to the spinal cord could form a feedback loop for control of spinal sensory, autonomic and motor activity.
Animals↗
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.
Animals↗
An ascending general homeostatic afferent pathway originating in lamina I.
Explore the source record for details and available documents.
Afferent Pathways↗
Cooling-specific spinothalamic neurons in the monkey.
1. Little is known concerning the processing of innocuous thermoreceptive information in the CNS of the monkey. The aim of the present study was to confirm the prediction, based on recent studies in cat and monkey, that there must be a prominent spinothalamic (STT) projection of cooling-specific spinal cord lamina I neurons to the posterior part of the ventral medial nucleus (VMpo) of the monkey thalamus. 2. Experiments were performed on four cynomolgus monkeys anesthetized with pentobarbital sodium. A detailed mapping of somatosensory thalamus was performed in each animal, and VMpo was identified by recordings from clusters of thermoreceptive-specific and nociceptive-specific (NS) neurons. Stimulating electrodes were then implanted in VMpo. Tungsten microelectrodes were used to record the responses of neurons in the superficial dorsal horn of the lumbosacral spinal cord. 3. Many spontaneously active lamina I neurons were found that were inhibited by radiant warming and that responded to innocuous cooling of the hindpaw. These cooling-specific (COLD) neurons were excited by small temperature drops below skin temperature and increased their discharge with decreasing skin temperature. They were not excited by thermally neutral mechanical stimuli applied to the receptive fields. In passing, we also characterized with natural stimulation a few NS neurons reponsive to pinch and/ or noxious heat, multimodal (HPC) neurons responsive to noxious heat, pinch, and cold stimuli, and wide-dynamic-range neurons responsive to both innocuous and noxius cutaneous stimuli that were encountered in lamina I. 4. Twenty lamina I COLD cells were identified as STT neurons by antidromic activation from the contralateral VMpo. The mean conduction latency for these units was 26.1 ms, which corresponds to a mean conduction velocity of approximately 8.0 m/s. They were not antidromically activated from an electrode in the region of the ventral posterior nucleus in the thalamus. In addition, we antidromically activated from VMpo four NS units and three HPC cells. 5. These findings demonstrate for the first time the existence of a prominent direct projection of specific COLD lamina I STT cells to thalamus in the monkey. This is consistent with clinical inferences in humans and with prior results in cats. This result confirms that the dense lamina I STT projection to VMpo demonstrated in anatomic studies includes COLD cells, and it supports the role of VMpo as a thalamic relay nucleus for pain- and temperature-related information.
Animals↗
Distribution of brainstem projections from spinal lamina I neurons in the cat and the monkey.
The distribution of terminal projections in the brainstem from lamina I neurons in the spinal dorsal horn was investigated with the anterograde tracer Phaseolus vulgaris-leucoagglutinin in the cat and the cynomolgus monkey. Iontophoretic injections made with physiological guidance were restricted to lamina I or to laminae I-III in the cervical (C6-8) or lumbar (L6-7) enlargement. The distribution of terminal labeling was essentially identical in the cat and the monkey, although consistently of greater intensity in the monkey. Terminations were observed in the solitary nucleus, the dorsomedial medullary reticular formation, the entire rostrocaudal extent of the ventrolateral medulla, the locus coeruleus, the subcoerulear region and the Kölliker-Fuse nucleus, the lateral and medial portions of the parabrachial nucleus, the cuneiform nucleus, the ventrolateral and lateral portions of the periaqueductal gray, and the intercollicular nucleus. Lamina I terminations were generally bilateral in the medulla but more dense contralaterally in the pons and mesencephalon. The density and laterality of labeling in the medulla varied between cases independently from that in the pons and mesencephalon, suggesting that the lamina I projections to these regions may originate from different subsets of neurons. A clear topographic organization was observed only in the lateral column of the periaqueductal gray, where lumbar lamina I terminations were found caudal to cervical terminations. These observations indicate that spinal lamina I neurons project to a variety of brainstem sites involved in autonomic (cardiovascular, respiratory) and homeostatic processing and the control of behavioral state. These projections provide an afferent substrate for spino-bulbo-spinal somatoautonomic reflex arcs activated by nociceptive, thermoreceptive activity and for a spino-bulbo-hypothalamic relay of such activity by cells in the caudal ventrolateral medulla. These observations support the general concept that lamina I projections distribute modality-selective sensory information relevant to the physiological status and maintenance of the tissues and organs of the entire organism.
Animals↗