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Biomedical subjects

A D Craig

Publications and source records attributed to A D Craig.

At least 55 records · Page 3Linked to original sources
PubMed1995

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.

Animals↗
PubMed1994

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.

Adult↗
PubMed1994

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.

Animals↗
PubMed1993

Propriospinal input to thoracolumbar sympathetic nuclei from cervical and lumbar lamina I neurons in the cat and the monkey.

The possibility that specific thermoreceptive and nociceptive influences on sympathetic outflow are conveyed directly to spinal sympathetic regions by lamina I neurons was investigated anatomically with the immunofluorescent PHA-L technique in the cat and the cynomolgus monkey. Iontophoretic injections made with physiological guidance were restricted to lamina I or to laminae I-II in the cervical (C6-8) or lumbar (L6-7) enlargement. Bilateral (symmetric) terminal arborizations were observed (with an ipsilateral predominance) in the intermediolateral, intermediomedial, and intervening regions of the thoracolumbar intermediate zone. In serial horizontal sections, patches of terminal labeling appeared at regular longitudinal intervals in the intermediolateral region. Longitudinally coursing fibers that had multiple varicosities and gave off small terminal branches were observed in the intermediolateral and the intermediomedial regions. Mediolateral strips of labeling that extended from labeling in the intermediolateral region to labeling in the intermediomedial region occurred at fairly regular longitudinal intervals. Because the longitudinal distribution of these terminations corresponds very well with the characteristic (ladder-like) longitudinal pattern of organization of the neuropil of the thoracolumbar sympathetic nuclei, i.e., the principal part of the intermediolateral cell column, the central autonomic n., and the intervening n. intercalatus, it is inferred that these lamina I terminations occur within these nuclei. After cervical injections, the labeling was most dense in the upper thoracic T2-4 spinal cord segments in both the cat and the monkey; labeling was also present in the T10-12 segments. After lumbar injections, labeling in the cat was located in the L4 segment; labeling in the monkey was present in the T4-6 and T10-12 segments. The labeling obtained was much more dense in the monkey than in the cat. These observations reveal a spinal lamina I projection that could provide a direct pathway for the somatosympathetic reflex effects of thermal and noxious stimuli. Considered together with reports that lamina I and the sympathetic nuclei both receive descending input from certain key autonomic regions, this result emphasizes the importance of lamina I for homeostasis, in addition to its probable roles in behavioral arousal, affect, and sensation. These observations thus support the proposed concept that lamina I processes and distributes in a functionally specific manner the sensory input relevant to the physiological status of the tissues and organs of the entire organism.

Animals↗
PubMed1992

Distribution of c-fos expression in brainstem neurons associated with conditioning and pseudo-conditioning of the rabbit nictitating membrane reflex.

Experiments were performed to test the hypothesis that there is a characteristic distribution of neuronal c-fos expression associated with the classical conditioning of the rabbit nictitating membrane reflex (NMR). Rabbits were divided into two groups: a conditioning group that received paired tone and airpuff stimuli in a traditional delay NMR conditioning paradigm and a pseudo-conditioning group in which the same number of tone and airpuff stimuli were applied but without being paired. Labeling was present in similar brainstem nuclei in both groups of animals. The labeled sites included trigeminal and auditory nuclei in the classical pathway for the nictitating membrane reflex as well as other nuclei such as the raphe nuclei and those in the ventrolateral medulla (VLM). However, there were quantitative differences in the labeling between the two groups. There were significantly more labeled nuclear profiles in the trigeminal nucleus of the pseudoconditioned rabbits, but more labeled nuclear profiles in the raphe nuclei in the conditioned animals. Interestingly, the ratio of the labeling in the raphe versus the VLM strongly differed between the two groups.

Animals↗
PubMed1992

Lamina I spinocervical tract terminations in the medial part of the lateral cervical nucleus in the cat.

The terminations of spinocervical tract fibers in the lateral cervical nucleus (LCN) of the cat were examined with anterogradely transported Phaseolus vulgaris leucoagglutinin (PHA-L) in order to analyze their organization relative to the most medial part and the main body (the lateral two-thirds) of the LCN, which have differential projections and physiological characteristics. Iontophoretic injections of PHA-L in laminae I-V of the spinal dorsal horn yielded dense labeling in somatotopically appropriate regions of the main body of the LCN, and, as seen previously with horseradish peroxidase, additional terminations were present in the medial LCN after injections at either cervical or lumbar spinal levels. The morphological characteristics of the PHA-L labeling in these two parts of the LCN were different. Terminations in the lateral LCN consisted of dense clusters of thick fibers bearing large numbers of boutons. The terminal axons in the medial part of the LCN displayed a reticulated network of longitudinally oriented, fine fibers with well-spaced varicosities. Some of the fine fibers in the medial LCN appeared to be collaterals of thicker fibers that terminated in the lateral LCN. Injections of PHA-L that were restricted to lamina I resulted in terminal labeling only in the medial LCN. The labeling was more sparse than that observed in the medial LCN after larger dorsal horn injections but displayed the same morphological characteristics. Lamina I terminations were seen in the medial LCN after cervical or lumbar injections on both the ipsilateral and contralateral sides. The PHA-L observations were corroborated by the presence of many retrogradely labeled lamina I cells at both cervical and lumbar spinal levels, following injections of cholera toxin subunit b or rhodamine-labeled microspheres in the medial LCN. In addition, double-immunofluorescent labeling for PHA-L and substance P was performed in a few cases, since substance P immunoreactivity is present in fibers in the medial LCN and also in cell bodies in lamina I; however, very few spinocervical fibers displayed immunoreactivity for both antigens. These observations indicate that the medial part of the LCN receives input from lamina I neurons, and probably from lamina III-V neurons as well, at cervical and lumbar spinal levels. The lamina I input to the medial LCN provides a basis for the small population of nociceptive neurons that differentiate the medial LCN. The lamina I input could also be responsible for the general inhibition of lateral LCN neurons by wide-field noxious stimulation, via activation of GABAergic interneurons in the medial LCN.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1992

Electron microscopic identification of lamina I axon terminations in the nucleus submedius of the cat thalamus.

Ascending lamina I axons were labeled with Phaseolus vulgaris leucoagglutinin and the synaptic connections of their terminals in nucleus submedius (Sm) were studied in the electron microscope. The terminals were large, contained rounded synaptic vesicles, and were involved in complex synaptic aggregations with pre- and postsynaptic dendrites. It was observed that clustered large boutons from a single axon could contact a single dendritic shaft. These observations support a sensory role for lamina I input to Sm.

Animals↗
PubMed1992

Spinal and trigeminal lamina I input to the locus coeruleus anterogradely labeled with Phaseolus vulgaris leucoagglutinin (PHA-L) in the cat and the monkey.

Terminal fibers anterogradely labeled with Phaseolus vulgaris leucoagglutinin (PHA-L) were observed in the locus coeruleus in the brainstem of the cat and the cynomolgus monkey following injections in lamina I of the spinal or medullary dorsal horn. Thus, thermoreceptive- or nociceptive-specific lamina I cells that project to the locus coeruleus could directly influence arousal, vigilance, and the descending control of spinal integration.

Animals↗
PubMed1991

Spinal distribution of ascending lamina I axons anterogradely labeled with Phaseolus vulgaris leucoagglutinin (PHA-L) in the cat.

The location of the ascending axons of spinal lamina I cells was studied in cats that received injections of Phaseolus vulgaris leucoagglutinin (PHA-L) in the superficial dorsal horn of the cervical or lumbosacral enlargement. Lamina I axons that could be ascribed to the spinothalamic tract (STT) were of particular interest. The cases were divided into three sets: in seven optimal cases the injections were restricted to lamina I; in ten nominal cases the injections involved laminae I-II or laminae I-III and occasionally lamina IV; and in eight mixed cases laminae I-V were injected. Since ipsilateral propriospinal and bilateral supraspinal axons originate from laminae I and V, but only ipsilateral propriospinal axons from laminae II-IV, this categorization facilitated a comparative analysis. Ascending axons labeled immunohistochemically with avidin/Texas Red were observed in oblique transverse sections from the C1, C3/4, T6, T12, and L3/4 levels. Incidental axonal labeling occurred in the ipsilateral dorsal columns because of passing primary afferent fiber uptake and, in nominal and mixed cases with involvement of laminae III-IV, in the superficial dorsolateral funiculus at the location of the spinocervical tract. Ipsilateral ascending lamina I axons in optimal cases were located in Lissauer's tract and in the white matter adjacent to the dorsal horn. Since these appeared to terminate in lamina I, and few remained at C1, they were ascribed to propriospinal projections. Contralateral ascending lamina I axons in optimal and nominal cases were distributed throughout the dorsal and ventral portions of the lateral funiculus (LF), but, despite considerable variability between animals in their location and dispersion, they were consistently concentrated in the middle of the LF (i.e., at the level of the central canal). This concentration was observed in a slightly more ventral location at C1, and a similar but weaker concentration of lamina I axons was located slightly more dorsally in C1 on the ipsilateral side. These supraspinal lamina I projections were ascribed to the spinomesencephalic tract (SMT) and to the STT. In mixed cases, additional ascending axons ascribed to lamina V cells were labeled in the ventrolateral and ventral funiculi. Many labeled axons were found in this region following a large injection of biocytin into lumbosacral laminae V-VIII in a supplementary case. These results thus together support previous descriptions of a dorsoventral distribution of STT axons according to laminar origin, but they contradict recent reports that lamina I axons ascend in the dorsolateral funiculus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Morphine enhances the activity of thermoreceptive cold-specific lamina I spinothalamic neurons in the cat.

The possibility that morphine might differentially affect spinal neurons responsive to small-diameter thermoreceptive-specific afferents was tested. Systemic morphine enhanced a portion or all of the stimulus-response function of 7 of 9 lamina I spinothalamic tract cells specifically sensitive to cold applied to the glabrous hindpaw in the cat. This result contrasts strongly with the predominant inhibition of nociceptive lamina I neurons by morphine.

Analysis of Variance↗
PubMed1989

Cells of origin of spinothalamic tract projections to the medial and lateral thalamus in the cat.

The double fluorescent retrograde labeling method was used to examine the distribution of spinothalamic tract (STT) cells that project to the medial and lateral thalamus in the cat. Injections of one fluorescent tracer (Fast Blue or Diamidino Yellow) were made throughout the lateral thalamus and injections of the other tracer were made in the medial thalamus at sites extrapolated from recording track coordinates. Survival times were successively extended (up to 5 weeks) in order to maximize labeling in both the cervical and lumbosacral spinal cord. On average, over 2,000 labeled contralateral STT cells were counted in serial sections from segments C5-7 and L5-S2. Numerical variability of the order of a factor of two was attributable to inherent differences between individual animals. The total number of cells labeled with fluorescent tracers was comparable to the number labeled with horseradish peroxidase in control cases, although there were significant differences between the laminar distributions of labeling produced by the two methods. Injections made anterior to the thalamus to control for labeling due to leakage or passing fibers did not produce substantial spinal labeling. The laminar distribution of fluorescent dye-labeled STT cells was consistent; about half (47%) were located in lamina I, 8% were in lamina V, 5% in lamina VI, 20% in lamina VII, and 20% in lamina VIII. The proportions of STT cells in laminae I and V were higher in cervical segments (57% and 12%, respectively) than in lumbosacral segments (38% and 6%). The dominant contribution of lamina I cells to the STT thus revealed by the fluorescent tracers is striking. The proportions of STT cells labeled from the medial and the lateral thalamus varied with segmental and laminar location and with injection placement. The majority (62%) of STT cells in most cases projected only to the medial thalamus, 25% projected only to the lateral thalamus, and 13% projected to both. The STT cell populations in laminae I, VII, and VIII each displayed this common projection pattern. In contrast, cells in laminae V and VI projected predominantly to the lateral thalamus. Twice as many STT cells in lamina I (19%) projected to both the medial and the lateral thalamus as from other laminae. A greater proportion of laminae V-VIII STT cells in segments L5-6 projected to the lateral thalamus, and in S1-2, more projected to the medial thalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

Amidines↗
PubMed1989

Significant differences in the retrograde labeling of spinothalamic tract cells by horseradish peroxidase and the fluorescent tracers fast blue and diamidino yellow.

The laminar distributions of spinothalamic tract cells retrogradely labeled by the fluorescent tracers Fast Blue and Diamidino Yellow and by free or lectin-coupled horseradish peroxidase have been found to be significantly different. The total numbers of cells labeled by each method are similar, but nearly twice as many lamina I cells are labeled by the fluorescent tracers and more lamina V cells are labeled by peroxidase. Injection site spread and spurious labeling due to leakage or fibers of passage do not account for these differences. These results indicate that both horseradish peroxidase and fluorescent tracers may be selectively transported and, thus, that the cautious use of both methods should be recommended for analyses of afferent populations.

Amidines↗
PubMed1988

The projection of the medial and posterior articular nerves of the cat's knee to the spinal cord.

We studied the spinal projections of the medial and posterior articular nerves (MAN and PAN) of the knee joint in the cat with the aid of the transganglionic transport of horseradish peroxidase. The afferent fibers of the MAN entered the spinal cord via the lumbar dorsal roots L5 and L6 and those of the PAN entered via the dorsal roots L6 and L7. Within the dorsal root ganglia, most labeled neurons had small to medium diameters. A relatively higher number of medium-size cell bodies were labeled from the PAN than from the MAN. In the spinal cord labeled MAN afferent fibers and terminations were most dense in the L5 and L6 segments, and those of the PAN were most dense in L6 and L7, that is, in the respective segments of entry. Labeled afferent fibers from both nerves projected rostrally at least as far as L1 and caudally as far as S2. Labeled fibers were found in Lissauer's tract as well as in the dorsal column immediately adjacent to the dorsal horn. In the spinal gray matter, both nerves had two main projection fields, one in the cap of the dorsal horn in lamina I, the other in the deep dorsal horn in laminae V-VI and the dorsal part of lamina VII. Both nerves, but particularly the PAN, projected to the medial portion of Clarke's column. No projection was found to laminae II, III, and IV of the dorsal horn or to the ventral horn. Since these findings parallel observations on hindlimb muscle afferent fibers, the present data support the existence of a common pattern for the central distribution of deep somatic afferent fibers.

Afferent Pathways↗
PubMed1988

Spinal and supraspinal terminations of primary afferent fibers from the gastrocnemius-soleus muscle in the cat.

The central distribution of the terminations of primary afferent fibers from the gastrocnemius-soleus muscle in the cat was examined with the method of transganglionic transport of horseradish peroxidase. At the segmental level, the main projection areas were found to be laminae I and V-VII; in the rostrocaudal direction, the terminations extended from the third sacral segment to nucleus Z. A 40% solution of horseradish peroxidase in 2% dimethylsulfoxide was applied to the central cut ends of the muscle nerves in an open pool for several hours and subsequently was removed. A capsule of tracer solution applied during the survival period of the animals was found to result in additional labeling due to peripheral leakage. The tissue sections were processed with tetramethylbenzidine. Termination fields were consistently observed ipsilaterally in: lamina I from the L4 through S3 segments, being most dense in L6 and S1; lateral lamina V in L6 and S1-3; medial laminae VI-VII from L5 through S3; medial Clarke's column from L1 through L4; the ventral aspect of the gracile nucleus; and, nucleus Z. Little or no labeling was found in laminae II-IV in experiments in which peripheral leakage of tracer solution was prevented. The distribution of reaction product in laminae VI-VII and Clarke's column corresponds to the projections of large-diameter afferent fibers from the gastrocnemius-soleus muscle. The projections to laminae I and V, which are attributed to small-diameter sensory fibers, indicate involvement of these laminae in sensory modalities mediated by slowly conducting muscle afferent fibers, e.g. deep nociception. This pattern contrasts strongly with the central projections of cutaneous fibers, which terminate heavily in laminae II-IV, but resembles the central distribution of fibers from tooth pulp and viscera.

Afferent Pathways↗
PubMed1987

Organization of anterogradely labeled spinocervical tract terminations in the lateral cervical nucleus of the cat.

The anterograde transport of horseradish peroxidase following injections into the cervical, thoracic, or lumbosacral spinal cord was used to examine the organization of spinocervical tract terminations in the lateral cervical nucleus (LCN) of the cat. A somatotopic organization of the labeling originating from different spinal levels was observed in the mediolateral dimension. Cervical labeling generally occurred in the ventromedial portion and lumbosacral labeling in the dorsolateral portion of the LCN. Thoracic labeling occurred both in the middle and the most lateral edge of the nucleus. In all cases, labeling was distributed over most of the rostrocaudal extent of the LCN. In addition, distinct patches of labeling were present in the medialmost portion of the nucleus, regardless of the spinal level injected. These observations corroborate the topographical organization of the LCN described previously on the basis of physiological and retrograde labeling data, and support the identification of the medialmost part of the LCN as a distinct portion of the nucleus. Terminal labeling in the LCN always occurred in multiple, longitudinally distributed fields. The afferent input to each terminal field coursed in separate, loose bundles of fibers that descended from the superficial dorsolateral funiculus. Large injections resulted in more extensive, overlapping terminal fields. These observations indicate that collateral projections result in several discrete representations of a given portion of the skin over the longitudinal extent of the LCN, but that topographical relationships are longitudinally maintained. It is suggested that these multiple terminal fields are the anatomical correlate of the functionally selective convergence of spinocervical tract terminations, that has previously been postulated on physiological grounds to explain the generation of LCN receptive fields with homogenous receptor input within a somatotopic framework.

Animals↗
PubMed1985

The distribution and topographical organization in the thalamus of anterogradely-transported horseradish peroxidase after spinal injections in cat and raccoon.

The distribution of anterogradely-transported horseradish peroxidase (HRP) was examined in the rostral mesencephalon and thalamus of cats and raccoons that had received injections of HRP in the cervical and/or lumbosacral enlargements of the spinal cord. Labeling was consistently observed in a large number of loci. All regions previously identified as targets of spinomesencephalic or spinothalamic fibers were included. Evidence of topographical organization was obtained in several regions. Adjacent fields of labeling were often separable on the basis of the distribution, appearance and topographical organization of the labeling. Subject to the methodological constraints imposed by the possibilities of transneuronal and/or collateral labeling, we conclude that a wide variety of loci in the thalamus receive direct spinal input. The organization of these projections suggests that each terminal region may be associated with different aspects of spinal cord function.

Animals↗
PubMed1985

Spinothalamic lumbosacral lamina I cells responsive to skin and muscle stimulation in the cat.

The response characteristics of lamina I neurones recorded extracellularly in the lumbosacral enlargement of chloralose-anaesthetized cats were examined with peripheral nerve electrical stimulation, adequate mechanical and thermal stimulation of hind-limb skin, and algesic mechanical and chemical stimulation of musculotendinous structures, particularly the gastrocnemius-soleus (g.s.) muscle. Antidromic activation from an electrode array that spanned the contralateral thalamus was used to identify lamina I spinothalamic tract (lam.I-s.t.t.) neurones. Recordings were made from a total of 218 lumbosacral lam.I-s.t.t. neurones. Their mean central conduction latency was 90.1 ms (range 20-300 ms), corresponding to a mean conduction velocity of 3.7 m/s (range 1.1-16.7). Neurones responsive only to peripheral A delta fibre stimulation had significantly shorter central conduction latencies (mean = 62.8 ms) than those with both A delta and C fibre input (mean = 81.9 ms) and those with only C fibre input (mean = 134.6 ms). Of these 218 neurones, 103 (47%) projected only to medial thalamus, 41 (19%) only to lateral thalamus, and 56 (26%) to both; 18 (8%) were classified as mid-thalamic projecting cells. About 10% of all cells had ongoing activity when first isolated. Ninety-three lam.I-s.t.t. neurones responded to stimulation of the sciatic nerve. The response characteristics of forty-seven of these were examined with the complete set of stimuli used. Twenty-four non-s.t.t. lamina I neurones were also characterized for comparison. Twenty-eight of the lam.I-s.t.t. neurones tested with the complete set of stimuli responded specifically to either cutaneous noxious (n = 19), cutaneous innocuous cold (n = 6) or algesic musculo-tendinous (n = 3) stimulation. Thirteen neurones responded to cutaneous noxious stimulation, and, in addition, to cold stimulation (n = 6), to deep stimulation (n = 4), or to both (n = 3). Six cells did not respond to any of the natural stimuli employed. All of the cold-specific and many of the multireceptive cold-sensitive neurones had ongoing discharge. The average central conduction latencies of cold-sensitive neurones (65.5 ms) and unresponsive neurones (48.7 ms) were shorter than that of nociceptive neurones (91.2 ms). Two response categories had distinct thalamic projection patterns. The majority of cold-specific neurones projected only to medial thalamus. Almost all multireceptive cold-sensitive neurones projected to both medial and lateral thalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗