PubMed Health⌕ Search

Biomedical subjects

A D Craig

Publications and source records attributed to A D Craig.

At least 19 recordsLinked to original sources
PubMed2005

Vagal-evoked activity in the parafascicular nucleus of the primate thalamus.

The physiological effects of ascending vagal afferent activity in the primate forebrain have not been established, and because vagus nerve stimulation (VNS) is useful clinically for treatment of epilepsy and depression, these actions need to be identified. We used a roving microelectrode to record vagal-evoked potentials in the thalamus of the macaque monkey. In addition to the anticipated activation in the gustatory/visceral thalamic relay nucleus, we found an unexpectedly larger and earlier response focus with multi-unit discharges in the adjacent parafascicular nucleus. These data reveal a potent vagal input to this intralaminar nucleus, which is normally considered to be involved in motor control. This finding indicates that a role for this vagal activation site in the anti-epileptic effects of VNS needs to be considered.

Animals↗
PubMed2004

Distribution of trigeminothalamic and spinothalamic lamina I terminations in the macaque monkey.

Thalamic terminations from trigeminal, cervical, and lumbosacral lamina I neurons were investigated with Phaseolus vulgaris leucoagglutinin (PHA-L) and labeled dextrans. Iontophoretic injections guided by physiological recordings were restricted to lamina I or laminae I-II. PHA-L-labeled trigemino- and spinothalamic (TSTT) terminations were identified immunohistochemically. TRITC- and FITC-labeled dextrans were injected at different levels to confirm topography. Terminations consistently occurred in two main locations: a distinguishable portion of posterolateral thalamus identified cytoarchitectonically as the posterior part of the ventral medial nucleus (VMpo) and a portion of posteromedial thalamus designated as the ventral caudal part of the medial dorsal nucleus (MDvc). In addition, isolated fibers bearing boutons of passage were observed in the ventral posterior medial and lateral (VPM and VPL) nuclei, and spinal terminations occurred in the ventral posterior inferior nucleus (VPI). Isolated terminations occasionally occurred in other sites (e.g., suprageniculate, zona incerta, hypothalamic paraventricular n.). Terminations in MDvc occurred in concise foci that were weakly organized topographically (posteroanterior = rostrocaudal). Terminations in VMpo consisted of dense clusters of ramified terminal arbors bearing multiple large boutons that were well organized topographically (anteroposterior = rostrocaudal). Terminations in VMpo colocalized with a field of calbindin-immunoreactive terminal fibers; double-labeled terminals were documented at high magnification. This propitious marker was especially useful at anterior levels, where VMpo can easily be misidentified as VPM. These findings demonstrate phylogenetically novel primate lamina I TSTT projections important for sensory and motivational aspects of pain, temperature, itch, muscle ache, sensual touch, and other interoceptive feelings from the body.

Animals↗
PubMed2004

Lamina I, but not lamina V, spinothalamic neurons exhibit responses that correspond with burning pain.

Single-unit recordings from monkey spinothalamic tract (STT) neurons reveal that the responses of polymodal nociceptive lamina I STT neurons correspond with the profile of burning pain elicited in human subjects by repeated brief-contact heat. In contrast, lamina V wide-dynamic-range (WDR) neurons show a significantly different response pattern. This finding indicates that burning pain is signaled by modality-selective lamina I neurons and not convergent lamina V WDR neurons.

Animals↗
PubMed2003

Synaptology of trigemino- and spinothalamic lamina I terminations in the posterior ventral medial nucleus of the macaque.

We used the electron microscope to examine lamina I trigemino- and spinothalamic (TSTT) terminations in the posterior part of the ventral medial nucleus (VMpo) of the macaque thalamus. Lamina I terminations were identified by anterograde labeling with biotinylated dextran, and 109 boutons on 38 terminal fibers were closely studied in series of ultrathin sections. Five unlabeled terminal boutons of similar appearance were also examined in detail. Three-dimensional, volume-rendered computer models were reconstructed from complete series of serial sections for 29 boutons on 10 labeled terminal fibers and one unlabeled terminal fiber. In addition, postembedding immunogold staining for GABA was obtained in alternate sections through 23 boutons. Lamina I TSTT terminations in VMpo generally have several large boutons (mean length = 2.16 microm, mean width = 1.29 microm) that are densely packed with vesicles and make asymmetric synaptic contacts on low-order dendrites of VMpo neurons (mean diameter 1.45 microm). They are closely associated with GABAergic presynaptic dendrites (PSDs), and nearly all form classic triadic arrangements (28 of 29 reconstructed boutons). Consecutive boutons on individual terminal fibers make multiple contacts with a single postsynaptic dendrite and can show evidence of progressive complexity. Dendritic appendages that enwrap and invaginate the terminal bouton constitute additional anatomic evidence for secure, high-fidelity synaptic transfer. These observations provide direct ultrastructural evidence supporting the hypothesis that VMpo is a lamina I TSTT thalamocortical relay nucleus in primates that subserves pain, temperature, itch, and other sensations related to the physiological condition of the body.

Animals↗
PubMed2003

A new view of pain as a homeostatic emotion.

Pain is conventionally viewed as a pattern of convergent activity within the somatosensory system that represents the exteroceptive sense of touch. Accumulating functional, anatomical and imaging findings indicate that pain is generated by specific sensory channels that ascend in a central homeostatic afferent pathway. Phylogenetically new thalamocortical projections in primates provide a sensory image of the physiological condition of the body and, in addition, direct activation of limbic motor cortex. These findings indicate that the human feeling of pain is both a distinct sensation and a motivation - that is, a specific emotion that reflects homeostatic behavioral drive, similar to temperature, itch, hunger and thirst.

Animals↗
PubMed2003

Interoception: the sense of the physiological condition of the body.

Converging evidence indicates that primates have a distinct cortical image of homeostatic afferent activity that reflects all aspects of the physiological condition of all tissues of the body. This interoceptive system, associated with autonomic motor control, is distinct from the exteroceptive system (cutaneous mechanoreception and proprioception) that guides somatic motor activity. The primary interoceptive representation in the dorsal posterior insula engenders distinct highly resolved feelings from the body that include pain, temperature, itch, sensual touch, muscular and visceral sensations, vasomotor activity, hunger, thirst, and 'air hunger'. In humans, a meta-representation of the primary interoceptive activity is engendered in the right anterior insula, which seems to provide the basis for the subjective image of the material self as a feeling (sentient) entity, that is, emotional awareness.

Afferent Pathways↗
PubMed2003

Distribution of trigeminothalamic and spinothalamic lamina I terminations in the cat.

The distribution in the thalamus of terminal projections from lamina I neurons of the trigeminal, cervical, and lumbosacral dorsal horn was investigated with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in the cat. Iontophoretic injections were guided by single- and multi-unit physiological recordings. The injections in particular cases were essentially restricted to lamina I, whereas in others they spread across laminae I-III or laminae I-V. The trigemino- and spinothalamic (TSTT) terminations were identified immunohistochemically. In all cases, regardless of the level of the injections, terminal fibers were consistently distributed in three main locations: the submedial nucleus; the ventral aspect of the basal ventral medial nucleus and ventral posterior nuclei; and, the dorsomedial aspect of the ventral posterior medial nucleus. The terminal fields in the submedial nucleus and the ventral aspect of the ventral posterior group were topographically organized. Terminations along the ventral aspect of the ventral posterior group extended posterolaterally into the caudal part of the posterior nucleus and anteromedially into the ventromedial part of the ventral lateral nucleus. In several cases with trigeminal lamina I injections, a terminal labeling patch was observed within the core of the ventral posterior medial nucleus. In cases with spinal lamina I injections, terminations were also consistently found in the lateral habenula, the parafascicular nucleus, and the nucleus reuniens. Isolated terminal fibers were occasionally seen in the zona incerta, the dorsomedial hypothalamus, and other locations. These anatomical observations extend prior studies of TSTT projections and identify lamina I projection targets that are important for nociceptive, thermoreceptive, and homeostatic processing in the cat. The findings are consistent with evidence from physiological (single-unit and antidromic mapping) and behavioral studies. The novel identification of spinal lamina I input to the lateral habenula could be significant for homeostatic behaviors.

Animals↗
PubMed2002

Association of spinothalamic lamina I neurons and their ascending axons with calbindin-immunoreactivity in monkey and human.

The calbindin-immunoreactivity of spinothalamic (STT) lamina I neurons and their ascending axons was examined in two experiments. In the first experiment, lamina I STT neurons in macaque monkeys were double-labeled for calbindin and for retrogradely transported WGA*HRP following large (n=2) or small (n=1) injections that included the posterior thalamus. Most, but not all (78%) of the contralateral retrogradely labeled lamina I STT cells were positive for calbindin. Calbindin-immunoreactivity was not selectively associated with any particular anatomical type of lamina I STT cell; 82% of the fusiform cells, 78% of the pyramidal cells and 67% of the multipolar cells were double-labeled. In the second experiment, oblique transverse sections from upper cervical spinal segments of three macaque monkeys, one squirrel monkey and five humans were stained for calbindin-immunoreactivity. In each case, a distinct bundle of fibers was densely stained in the middle of the lateral funiculus. This matches the location of anterogradely labeled ascending lamina I axons observed in prior work in cats and monkeys, and it matches the location of the classically described 'lateral spinothalamic tract' in humans. This bundle had variable shape across cases, an observation that might have clinical significance. These findings support the view that lamina I STT neurons are involved in spinal cordotomies that reduce pain, temperature and itch sensations.

Animals↗
PubMed2002

How do you feel? Interoception: the sense of the physiological condition of the body.

As humans, we perceive feelings from our bodies that relate our state of well-being, our energy and stress levels, our mood and disposition. How do we have these feelings? What neural processes do they represent? Recent functional anatomical work has detailed an afferent neural system in primates and in humans that represents all aspects of the physiological condition of the physical body. This system constitutes a representation of 'the material me', and might provide a foundation for subjective feelings, emotion and self-awareness.

Afferent Pathways↗
PubMed2002

Responses of spinothalamic lamina I neurons to maintained noxious mechanical stimulation in the cat.

Noxious mechanical stimuli that are maintained for minutes produce a continuous sensation of pain in humans that augments during the stimulus. It has recently been shown with systematic force-controlled stimuli that, while all mechanically responsive nociceptors adapt to these stimuli, the basis for such pain can be ascribed to A-fiber rather than C-fiber nociceptors, based on distinctions in their respective response profiles and stimulus-response functions. The present experiments investigated whether similar distinctions could be made in subsets of nociceptive lamina I spinothalamic tract (STT) neurons using similar maintained stimuli. Twenty-eight lamina I STT neurons in the lumbosacral dorsal horn of barbiturate-anesthetized cats were tested with noxious mechanical stimuli applied with a probe of 0.1 mm(2) contact area at forces of 25, 50, and 100 g for 2 min. The neurons were classified as nociceptive-specific (NS, n = 14) or polymodal nociceptive (HPC, n = 14) based on their responses to quantitative thermal stimuli. The NS neurons had greater responses and showed less adaptation than the HPC neurons in response to these stimuli, and they encoded stimulus intensity better. Comparison of the normalized response profiles of all 28 nociceptive lamina I STT neurons, independent of cell classification, revealed 2 subgroups that differed significantly: "Maintained" cells with responses that remained above 50% of the initial peak rate during stimulation and "Adapting" cells with responses that quickly declined to <50%. The Maintained neurons encoded the intensity of the mechanical stimuli better than the Adapting neurons, based on ratiometric functions. A k-means cluster analysis of all 28 cells distinguished the identical two subgroups. These categories corresponded closely to the NS and HPC categories: Maintained cells were mostly NS neurons (10 NS, 3 HPC), and Adapting cells were mostly HPC neurons (4 NS, 11 HPC). Thus the present data are consistent with the distinctions between A-fiber and C-fiber nociceptors observed previously, because A-fiber nociceptors are the predominant input to NS lamina I STT neurons and C-fiber nociceptors are the predominant input to HPC neurons. These findings support the view that NS, but perhaps not HPC, lamina I STT neurons have a role in the pain caused by maintained mechanical stimuli and contribute to the sensations of "first" pain and "sharpness." Nonetheless, none of the units studied showed increasing responses during the stimuli, suggesting a role for other ascending neurons or forebrain integration in the augmenting pain produced by maintained mechanical stimulation.

Animals↗
PubMed2002

Responses of spinothalamic lamina I neurons to repeated brief contact heat stimulation in the cat.

It was recently shown that repeated heat stimulation, using brief contacts (<1 s) with a preheated thermode at sufficiently short interstimulus intervals (ISIs <5 s) and high temperatures (> or =51 degrees C), will elicit in humans a sensation of rapidly augmenting "second" (burning) pain with only a weak "first" (sharp) pain sensation. Most strikingly, at short intertrial intervals (ITIs >5 s) such summation will reset, or begin again at baseline. In the present experiments, the responses of nociceptive lamina I spinothalamic (STT) neurons in the lumbosacral dorsal horn of barbiturate-anesthetized cats were examined using this repeated brief contact heat paradigm. The neurons were classified as nociceptive-specific (NS, n = 8) or polymodal nociceptive (HPC, n = 8) based on their responses to quantitative thermal stimuli; all had receptive fields on the glabrous ventral hindpaw. A pneumatic piston was used to apply a thermode preheated to 34, 46, 49, 53, or 58 degrees C with a contact dwell time of approximately 0.7 s to the ventral hindpaw repeatedly (15 times) at ISIs of 2, 3, and 5 s, with 3-5 min between trials. The mean responses of the 16 nociceptive lamina I STT cells showed rapid temporal summation that was directly dependent on temperature and inversely dependent on ISI, with the greatest increases occurring between the 3rd and 10th contacts. The temporal profiles of this family of curves correspond with the psychophysical data on human sensation. Further analysis showed that this summation was due to the HPC cells, which all showed strong summation; in contrast, the NS cells showed little, if any. The HPC responses to the repeated heat stimuli lagged each contact by approximately 1 s, consistent with the strong, monosynaptic C-fiber input that is characteristic of HPC cells and also with the dependence of second pain on C-fiber nociceptors. HPC cells also displayed the reset phenomenon at short ITIs, again in correspondence with the psychophysical data. The summation and the reset displayed by HPC cells were not related to skin temperature. Thus the results presented in this study, together with those in the preceding article, demonstrate a double dissociation indicating that NS and HPC lamina I STT cells can subserve the qualitatively distinct sensations of first (sharp) and second (burning) pain, respectively. These findings support the concept that the lamina I STT projection comprises several discrete sensory channels that are integrated in the forebrain to generate distinct sensations.

Action Potentials↗
PubMed2002

Activation of spinobulbar lamina I neurons by static muscle contraction.

Spinal lamina I neurons are selectively activated by small-diameter somatic afferents, and they project to brain stem sites that are critical for homeostatic control. Because small-diameter afferent activity evoked by contraction of skeletal muscle reflexly elicits exercise-related cardiorespiratory activation, we tested whether spinobulbar lamina I cells respond to muscle contraction. Spinobulbar lamina I neurons were identified in chloralose-anesthetized cats by antidromic activation from the ipsilateral caudal ventrolateral medulla. Static contractions of the ipsilateral triceps surae muscle were evoked by tibial nerve stimulation using parameters that avoid afferent activation, and arterial blood pressure responses were recorded. Recordings were maintained from 13 of 17 L(7) lamina I spinobulbar neurons during static muscle contraction, and 5 of these neurons were excited. Three were selectively activated only by muscle afferents and did not have a cutaneous receptive field. Spinobulbar lamina I neurons activated by muscle contraction provide an ascending link for the reflex cardiorespiratory adjustments that accompany muscular work. This study provides an important first step in elucidating an ascending afferent pathway for somato-autonomic reflexes.

Animals↗
PubMed2001

Spinothalamic lamina I neurones selectively responsive to cutaneous warming in cats.

1. In order to further characterize the role of lamina I as the source of central ascending neural pathways for thermoreception and thermoregulation, experiments were performed on anaesthetized cats to determine the quantitative response characteristics of warming-specific lumbosacral spinothalamic lamina I neurones. 2. We identified 10 neurones out of 474 that were selectively excited by cutaneous warming (Warm cells). Their thresholds were all in the range 35-37 degrees C at a baseline of 34.5 degrees C, and their discharge linearly encoded the temperature of graded, innocuous warming stimuli with a sensitivity of 2.1 Hz x degrees C(-1). 3. The stimulus-response function of the Warm cells plateaued at temperatures that were in the noxious heat range. 4. The Warm cells were distinguished from other classes of spinothalamic lamina I neurones by their peripheral inputs, central conduction velocities and level of ongoing activity. 5. The discharge of Warm cells compares well with the known human psychophysics of warm sensibility, and these neurones are likely to be crucial to discriminative thermoreception. Additionally, a role in thermoregulation, a defining feature of mammalian homeostasis, is suggested.

Afferent Pathways↗
PubMed2001

Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch.

We found a class of lamina I spinothalamic tract (STT) neurons selectively excited by iontophoretic histamine. The responses of this class of neurons parallel the pure itching sensation this stimulus elicits in humans, and match the responses of peripheral C-fibers that have similar selectivity. These neurons have distinct central conduction velocities and thalamic projections, indicating that they constitute a unique subset of STT neurons. These findings can explain why a lesion of the lateral STT disrupts itch along with pain and temperature sensations. Our findings provide strong evidence that itch is subserved by specific neural elements both peripherally and centrally.

Animals↗
PubMed2001

Differential projections of thermoreceptive and nociceptive lamina I trigeminothalamic and spinothalamic neurons in the cat.

The projections of 40 trigeminothalamic or spinothalamic (TSTT) lamina I neurons were mapped using antidromic activation from a mobile electrode array in barbiturate anesthetized cats. Single units were identified as projection cells from the initial array position and characterized with natural cutaneous stimuli as nociceptive-specific (NS, n = 9), polymodal nociceptive (HPC, n = 8), or thermoreceptive-specific (COOL, n = 22; WARM, n = 1) cells. Thresholds for antidromic activation were measured from each electrode in the mediolateral array at vertical steps of 250 microm over a 7-mm dorsoventral extent in two to eight (median = 6.0) anteroposterior planes. Histological reconstructions showed that the maps encompassed all three of the main lamina I projection targets observed in prior anatomical work, i.e., the ventral aspect of the ventroposterior complex (vVP), the dorsomedial aspect of the ventroposterior medial nucleus (dmVPM), and the submedial nucleus (Sm). The antidromic activation foci were localized to these sites (and occasional projections to other sites were also observed, such as the parafascicular nucleus and zona incerta). The projections of thermoreceptive and nociceptive cells differed. The projections of the thermoreceptive-specific cells were 20/23 to dmVPM, 21/23 to vVP, and 17/23 to Sm, whereas the projections of the NS cells were 1/9 to dmVPM, 9/9 to vVP, and 9/9 to Sm and the projections of the HPC cells were 0/8 to dmVPM, 7/8 to vVP, and 6/8 to Sm. Thus nearly all thermoreceptive cells projected to dmVPM, but almost no nociceptive cells did. Further, thermoreceptive cells projected medially within vVP (including the basal ventral medial nucleus), while nociceptive cells projected both medially and more laterally, and the ascending axons of thermoreceptive cells were concentrated in the medial mesencephalon, while the axons of nociceptive cells ascended in the lateral mesencephalon. These findings provide evidence for anatomical differences between these physiological classes of lamina I cells, and they corroborate prior anatomical localization of the lamina I TSTT projection targets in the cat. These results support evidence indicating that the ventral aspect of the basal ventral medial nucleus is important for thermosensory behavior in cats, consistent with the view that this region is a primordial homologue of the posterior ventral medial nucleus in primates.

Afferent Pathways↗
PubMed2001

Quantitative response characteristics of thermoreceptive and nociceptive lamina I spinothalamic neurons in the cat.

The physiological characteristics of antidromically identified lamina I spinothalamic (STT) neurons in the lumbosacral spinal cord were examined using quantitative thermal and mechanical stimuli in barbiturate-anesthetized cats. Cells belonging to the three main recognized classes were included based on categorization with natural cutaneous stimulation of the hindpaw: nociceptive-specific (NS), polymodal nociceptive (HPC), or thermoreceptive-specific (COOL) cells. The mean central conduction latencies of these classes differed significantly; NS = 130.8 +/- 55.5 (SD) ms (n = 100), HPC = 72.1 +/- 28.0 ms (n = 128), and COOL = 58.6 +/- 25.3 ms (n = 136), which correspond to conduction velocities of 2.5, 4.6, and 5.6 m/s. Based on recordings made prior to any noxious stimulation, the mean spontaneous discharge rates of these classes also differed: NS = 0.5 +/- 0.7 imp/s (n = 47), HPC = 0.9 +/- 0.7 imp/s (n = 59), and COOL = 3.3 +/- 2.6 imp/s (n = 107). Standard, quantitative, thermal stimulus sequences applied with a Peltier thermode were used to characterize the stimulus-response functions of 76 COOL cells, 47 HPC cells, and 37 NS cells. The COOL cells showed a very linear output from 34 degrees C down to approximately 15 degrees C and a maintained plateau thereafter. The HPC cells showed a fairly linear but accelerating response to cold below a median threshold of approximately 24 degrees C and down to 9 degrees C (measured at the skin-thermode interface with a thermode temperature of 2 degrees C). The HPC cells and the NS cells both showed rapidly increasing, sigmoidal response functions to noxious heat with a fairly linear response between 45 and 53 degrees C, but they had significantly different thresholds; half of the HPC cells were activated at ~45.5 degrees C and half of the NS cells at approximately 43 degrees C. The 20 HPC lamina I STT cells and 10 NS cells tested with quantitative pinch stimuli showed fairly linear responses above a threshold of approximately 130 g/mm(2) for HPC cells and a threshold of approximately 100 g/mm(2) for NS cells. All of these response functions compare well (across species) with the available data on the characteristics of thermoreceptive and nociceptive primary afferent fibers and the appropriate psychophysics in humans. Together these results support the concept that these classes of lamina I STT cells provide discrete sensory channels for the sensations of temperature and pain.

Animals↗