Abstract:. The primate posterior thalamus has been proposed to contribute to pain sensation, but its precise role is unclear. This is in part because spinothalamic tract (STT) neurons that project to the posterior thalamus have received little attention. In this study, antidromic mapping was used to identify individual STT neurons with axons that projected specifically to the posterior thalamus in Macaca fascicularis. Each axon was located by antidromic activation at low stimulus amplitudes (Ͻ30 A) and was then surroun… Show more
“…However, approximately one-fifth showed a very distinct temporal response in which a prolonged afterdischarge of EPSCs and action potentials outlasted the stimulus duration by several seconds (Figure 2H and I), consistent with previous findings from recordings in vivo (Woolf and Fitzgerald, 1983). Taken together, these experiments not only show feasibility of the semi-intact somatosensory preparation for the analysis of spatial and temporal responses, but also provide the first detailed analysis of the synaptic inputs received by lamina I neurons upon stimulation of the skin, thereby complementing and extending previous extracellular recordings in cat, rat and monkey (Craig et al, 2001; Craig and Andrew, 2002; Davidson et al, 2008; Jinks and Carstens, 1999; Zhang et al, 2006). …”
Section: Resultsmentioning
confidence: 52%
“…The other half appeared tuned to thermal stimuli, responding to either cold only (Figure 3D) or cold and heat (Figure 3E) as summarized (Figure 3F). Thus, our data show that the somatosensory preparation can be used to determine stimulus-response properties, and reveal for the first time that mouse spinal projection neurons in lamina I, like those in cat, rat and monkey, show modality-selective tuning (Craig et al, 2001; Davidson et al, 2008; Zhang et al, 2006). 10.7554/eLife.22866.005Figure 3.Modality tuning of projection neurons.( A ) Infrared (IR; left) and epifluorescent image (right) of lamina I projection neuron that was retrogradely labeled by injection of DiI into the lateral parabrachial nucleus.…”
The somatosensory input that gives rise to the perceptions of pain, itch, cold and heat are initially integrated in the superficial dorsal horn of the spinal cord. Here, we describe a new approach to investigate these neural circuits in mouse. This semi-intact somatosensory preparation enables recording from spinal output neurons, while precisely controlling somatosensory input, and simultaneously manipulating specific populations of spinal interneurons. Our findings suggest that spinal interneurons show distinct temporal and spatial tuning properties. We also show that modality selectivity — mechanical, heat and cold — can be assessed in both retrogradely labeled spinoparabrachial projection neurons and genetically labeled spinal interneurons. Finally, we demonstrate that interneuron connectivity can be determined via optogenetic activation of specific interneuron subtypes. This new approach may facilitate key conceptual advances in our understanding of the spinal somatosensory circuits in health and disease.DOI:
http://dx.doi.org/10.7554/eLife.22866.001
“…However, approximately one-fifth showed a very distinct temporal response in which a prolonged afterdischarge of EPSCs and action potentials outlasted the stimulus duration by several seconds (Figure 2H and I), consistent with previous findings from recordings in vivo (Woolf and Fitzgerald, 1983). Taken together, these experiments not only show feasibility of the semi-intact somatosensory preparation for the analysis of spatial and temporal responses, but also provide the first detailed analysis of the synaptic inputs received by lamina I neurons upon stimulation of the skin, thereby complementing and extending previous extracellular recordings in cat, rat and monkey (Craig et al, 2001; Craig and Andrew, 2002; Davidson et al, 2008; Jinks and Carstens, 1999; Zhang et al, 2006). …”
Section: Resultsmentioning
confidence: 52%
“…The other half appeared tuned to thermal stimuli, responding to either cold only (Figure 3D) or cold and heat (Figure 3E) as summarized (Figure 3F). Thus, our data show that the somatosensory preparation can be used to determine stimulus-response properties, and reveal for the first time that mouse spinal projection neurons in lamina I, like those in cat, rat and monkey, show modality-selective tuning (Craig et al, 2001; Davidson et al, 2008; Zhang et al, 2006). 10.7554/eLife.22866.005Figure 3.Modality tuning of projection neurons.( A ) Infrared (IR; left) and epifluorescent image (right) of lamina I projection neuron that was retrogradely labeled by injection of DiI into the lateral parabrachial nucleus.…”
The somatosensory input that gives rise to the perceptions of pain, itch, cold and heat are initially integrated in the superficial dorsal horn of the spinal cord. Here, we describe a new approach to investigate these neural circuits in mouse. This semi-intact somatosensory preparation enables recording from spinal output neurons, while precisely controlling somatosensory input, and simultaneously manipulating specific populations of spinal interneurons. Our findings suggest that spinal interneurons show distinct temporal and spatial tuning properties. We also show that modality selectivity — mechanical, heat and cold — can be assessed in both retrogradely labeled spinoparabrachial projection neurons and genetically labeled spinal interneurons. Finally, we demonstrate that interneuron connectivity can be determined via optogenetic activation of specific interneuron subtypes. This new approach may facilitate key conceptual advances in our understanding of the spinal somatosensory circuits in health and disease.DOI:
http://dx.doi.org/10.7554/eLife.22866.001
“…13,20,35 Furthermore, while many spinal cord and thalamic neurons respond to both noxious thermal and mechanical stimuli, there are those that only respond to noxious mechanical stimuli. 7,19 Thus, at the individual neuron level, nociceptive information initiated by heat vs. mechanical stimuli is partially segregated in the CNS. This separation of neural processing would be expected to play a role in perceptual differences, and result in increased inter-modality vs. intra-modality variance.…”
Many studies report that people with temporomandibular disorders (TMD) are more sensitive to experimental pain stimuli than TMD-free controls. Such differences in sensitivity are observed in remote body sites as well as in the orofacial region, suggesting a generalized upregulation of nociceptive processing in TMD cases. This large case-control study of 185 adults with TMD and 1,633 TMD-free controls measured sensitivity to painful pressure, mechanical cutaneous, and heat stimuli, using multiple testing protocols. Based on an unprecedented 36 experimental pain measures, 28 showed statistically significantly greater pain sensitivity in TMD cases than controls. The largest effects were seen for pressure pain thresholds at multiple body sites and cutaneous mechanical pain threshold. The other mechanical cutaneous pain measures and many of the heat pain measures showed significant differences, but with lesser effect sizes. Principal component analysis (PCA) of the pain measures derived from 1,633 controls identified five components labeled: (1) heat pain ratings, (2) heat pain aftersensations and tolerance, (3) mechanical cutaneous pain sensitivity, (4) pressure pain thresholds, and (5) heat pain temporal summation. These results demonstrate that, compared to TMD-free controls, chronic TMD cases are more sensitive to many experimental noxious stimuli at extra-cranial body sites, and provides for the first time the ability to directly compare the case-control effect sizes of a wide range of pain sensitivity measures.
“…The original description of VMpo was questioned by several authors (Wall, 1995; Willis et al, 2001, 2002; Ralston, 2003; Graziano and Jones, 2004; Davidson et al, 2008). Rebuttals to all criticisms have been published with detailed anatomical analyses and positive anatomical and physiological counter-evidence (Craig et al, 1995b; Craig and Blomqvist, 2002; Craig, 2004a,b, 2006, 2008, 2011).…”
Prior anterograde tracing work identified somatotopically organized lamina I trigemino- and spino-thalamic terminations in a cytoarchitectonically distinct portion of posterolateral thalamus of the macaque monkey, named the posterior part of the ventral medial nucleus (VMpo; Craig, 2004b). Microelectrode recordings from clusters of selectively thermoreceptive or nociceptive neurons were used to guide precise micro-injections of various tracers in VMpo. A prior report (Craig and Zhang, 2006) described retrograde tracing results, which confirmed the selective lamina I input to VMpo and the antero-posterior (head to foot) topography. The present report describes the results of micro-injections of anterograde tracers placed at different levels in VMpo, based on the antero-posterior topographic organization of selectively nociceptive units and clusters over nearly the entire extent of VMpo. Each injection produced dense, patchy terminal labeling in a single coherent field within a distinct granular cortical area centered in the fundus of the superior limiting sulcus. The terminations were distributed with a consistent antero-posterior topography over the posterior half of the superior limiting sulcus. These observations demonstrate a specific VMpo projection area in dorsal posterior insular cortex that provides the basis for a somatotopic representation of selectively nociceptive lamina I spinothalamic activity. These results also identify the VMpo terminal area as the posterior half of interoceptive cortex; the anterior half receives input from the vagal-responsive and gustatory neurons in the basal part of the ventral medial nucleus (VMb).
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