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Biomedical subjects

A I Basbaum

Publications and source records attributed to A I Basbaum.

At least 181 records · Page 10Linked to original sources
PubMed1983

The peptidergic organization of the cat periaqueductal gray. II. The distribution of immunoreactive substance P and vasoactive intestinal polypeptide.

Despite the important contribution of the midbrain periaqueductal gray (PAG) to endogenous pain suppression systems, little is known about the neuroanatomical basis of its functional organization. In a previous study of the distribution of the endogenous opiate leucine-enkephalin (ENK) in the PAG (Moss, M. S., E. J. Glazer, and A. I. Basbaum (1983) J. Neurosci. 3: 603-616), we found that immunoreactive ENK-containing neurons and terminals are clustered in discrete populations. In this study we have extended our analysis of the neurochemical organization of the PAG by using immunocytochemistry to map the distribution of two non-opiate peptides that produce potent analgesia when administered at central gray levels: substance P (Sub P) and vasoactive intestinal polypeptide (VIP). Immunoreactive Sub P neurons and terminal fields are clustered in discrete populations throughout the PAG. The distribution pattern of these populations changes at different rostral-caudal levels of the PAG. For example, there is a ventral-to-dorsal shift in the location of Sub P-like immunoreactivity from the caudal to the rostral PAG. Few immunoreactive Sub P neurons are found in the nucleus raphe dorsalis although moderately dense terminal field staining is present. The staining pattern of immunoreactive VIP is totally different from that of Sub P. Regardless of the rostral-caudal level examined, VIP-containing neurons are found tightly clustered in the subependymal neuropil of the ventromedial PAG. Only a few immunoreactive VIP-containing neurons are found in the ventral PAG or nucleus raphe dorsalis. The striking differences between the distribution of Sub P- and VIP-like immunoreactivity in the PAG indicates that the neural circuitry underlying pain suppression by Sub P and VIP may also differ.

Animals↗
PubMed1983

The peptidergic organization of the cat periaqueductal gray. I. The distribution of immunoreactive enkephalin-containing neurons and terminals.

Despite the significant contribution of the periaqueductal gray (PAG) to an endogenous pain suppression system, little is known about its neurochemical organization. Previous pharmacological and physiological studies have indicated regional variations in the effectiveness with which the midbrain PAG can generate potent analgesia in response to either opiate microinjection or electrical stimulation. There is, however, no anatomical correlate of this regional variation. As a first step toward elucidating the neural circuitry underlying the PAG's contribution to endogenous pain suppression systems, we have mapped the distribution of leucine enkephalin (ENK)-like immunoreactivity in the cat PAG. Throughout the rostral-caudal extent of the PAG, ENK-containing neurons are clustered in discrete populations. ENK terminal field staining is somewhat more diffuse; however, there are several regions where terminal staining is consistently more intense. The distribution of ENK perikarya and terminals undergoes a ventral to dorsal shift from caudal to rostral PAG. Conceivably, the clustered distribution of ENK cells and terminals contributes to the differential effectiveness of various PAG regions in generating analgesia. The ventral-dorsal shift of ENK immunoreactivity may (1) correspond to a somatotopic organization within the PAG or (2) mirror the topographic relationship of the PAG's interactions with other components of the endogenous analgesia system. In addition, the changing pattern of ENK immunoreactivity may also reflect the involvement of the PAG and of endogenous opiates in systems other than those of pain control.

Animals↗
PubMed1981

Afferent connections of the rostral medulla of the cat: a neural substrate for midbrain-medullary interactions in the modulation of pain.

In order to study the organization of the rostral medulla of the cat and its contribution to pain control mechanisms, we have examined the afferent connections of the midline nucleus raphe magnus (NRM), the laterally located nucleus reticularis magnocellularis (Rmc), and the nucleus reticularis gigantocellularis (Rgc) located dorsal to Rmc. Iontophoretic injections of HRP were made into the three regions; the distribution of retrogradely labeled neurons in brainstem and spinal cord was then mapped. While significant differences characterize the source of afferents to Rgc and NRM/Rmc, there is little to distinguish that between NRM and Rmc. The predominant spinal projection is to Rgc; fewer labeled neurons were recorded after injections into Rmc. In contrast, no significant direct spinal projection to NRM was found. All three regions receive input from widespread areas within the medullary and pontine reticular formation. The most pronounced differences in the distribution of retrogradely labeled neurons were found in the midbrain. The major projection to both NRM and Rmc derives from the periaqueductal gray (PAG) and from the adjacent nucleus cuneiformis. Labeled cells are concentrated in the dorsal and lateral PAG; few are found in the ventrolateral PAG. In contrast, Rgc receives few afferents from the PAG; however, after Rgc injections, many cells were recorded in the deep layers of the contralateral tectum. None of the injection sites produced significant labeling of the catecholamine-rich dorsolateral pontine tegmentum or of the nucleus raphe dorsalis. The demonstration of significant PAG projections to NRM/Rmc provides anatomical evidence for the hypothesis that opiate and stimulation-produced analgesia involves connections from PAG to neurons of NRM and Rmc which, in turn, inhibit spinal nociceptors.

Afferent Pathways↗
PubMed1981

Immunohistochemical localization of leucine-enkephalin in the spinal cord of the cat: enkephalin-containing marginal neurons and pain modulation.

This study examined the spinal cord distribution of the endogenous opioid peptide leucine-enkephalin in the cat using immunohistochemical techniques. The distribution of nerve processes was studied in untreated cats; colchicine was administered to study the distribution and morphology of spinal enkephalin-containing perikarya. Enkephalin immunoreactive processes were greatest in laminae I and II (marginal layer and substantia gelatinosa) of the superficial dorsal horn. In many sections, the outer substantia gelatinosa (SG), lamina IIa, was discernibly less immunoreactive than I or IIb. Laminae III and IV were relatively devoid of staining. Laminae V and VII had moderate enkephalin-immunoreactivity, lamina VI somewhat less. Enkephalin immunoreactivity in lamina X, around the central canal, was very dense. Enkephalin-containing beaded varicosities coursed throughout the ventral horn. Although previous studies in the rat emphasized the enkephalin-somata of the SG, we found that in the cat the majority of superficial dorsal horn enkephalin-somata are in the marginal layer. These enkephalin-containing marginal cells were morphologically similar to a population of marginal neurons which project to the brainstem and/or the thalamus. Some light staining small SG neurons were also identified; many were located at the lamina I-II border. Considerably more cells were found ventral to the SG, in lamina III, and at the IV-V border. These latter cells had dendrites coursing dorsally, toward the SG. Numerous immunoreactive cells were found in lamina VIII, in a band across the intermediate gray. These cells fused medially with cells of lamina X. Enkephalin cells were also found in the sacral autonomic nucleus and encircling the central cervical nucleus, Clarke's column, and stilling's nucleus. Although surrounded by labeled cells, the latter regions were devoid of enkephalin-immunoreactive processes. Many of these spinal enkephalin neurons are morphologically similar to and distributed in regions known to contain projection neurons. Thus it is suggested that many spinal enkephalin neurons, generally thought to be local circuit neurons, project rostrally, to other spinal levels and perhaps to brainstem and/or thalamus.

Animals↗
PubMed1981

Enkephalin-immunoreactive perikarya in the cat raphe dorsalis.

The serotonin-containing nucleus raphe dorsalis (RD) of the cat contains numerous leucine-enkephalin immunoreactive cells, throughout its rostral-caudal extent. The distribution of the enkephalin neurons closely parallels the cytoarchitectural boundaries of the RD, as described in previous Nissl preparations. Enkephalin perikarya are most numerous along the midline of the RD, but also extend ventrally, into the dorsal portion of the nucleus centralis superior, and laterally, into the 'wings' of the rostral RD, at the level of the IV nucleus. The possible contribution of these enkephalin cells to endogenous pain control systems is discussed.

Animals↗
PubMed1981

Serotonin neurons in nucleus raphe dorsalis and paragigantocellularis of the cat contain enkephalin.

1. The nucleus raphe dorsalis (RD) and paragiganto-cellularis (PGL) of the cat contain both 5-HT and leucine-enkephalin (ENK) immunoreactive perikarya. 2. Using a sequential immunoperoxidase-immunofluorescence technique for the localization of ENK and 5-HT, respectively, it was demonstrated that some PGL and RD neurons contain both the indoleamine and the peptide. 3. The double labeled neurons in the DR were characteristically small, round cells predominantly located on the midline of the nucleus, dorsal to the medial longitudinal fasciculus. Numerous large 5-HT containing perikarya were also found in the DR, but these cells did not contain ENK immunoreactivity.

Animals↗
PubMed1980

Leucine enkephalin: localization in and axoplasmic transport by sacral parasympathetic preganglionic neurons.

Nerve processes and cell bodies containing leucine enkephalin were demonstrated in the sacral autonomic nucleus of the cat by immunocytochemical methods. Enkephalinergic preganglionic perikarya were seen only when axonal transport was blocked either by colchicine or by ventral root ligation. Ligation of the sacral ventral roots also produced damming of enkephalin immunoreactivity proximal to the S2 ligature. These data indicate that parasympathetic preganglionic neurons synthesize and transport enkephalin or enkephalin-like immunoreactive compounds to the periphery.

Animals↗
PubMed1980

Dissociation of supraspinal and spinal actions of morphine: a quantitative evaluation.

Opiate suppression of spinal withdrawal reflexes was tested in rats with lesions of several spinal funiculi to determine the relative contribution of supraspinal descending systems. The latency of tail-flick to noxious heat was used to assess "analgesia". The effect of lesions of dorsolateral funiculus (DLF), dorsal columns (DC) and ventral quadrant (VQ) were compared to that of sham operations. None of the lesions produced a change in baseline latency. Each animal was tested with varying doses of morphine sulfate over several weeks. Only DLF lesions consistently antagonized tail-flick suppression by morphine across the dose range studied (5-15 mg/kg i.p.), although VQ lesions were somewhat effective. The reduction of morphine's action was proportionally greater for lower doses. The results indicate that both spinal and supraspinal sites contribute significantly to the analgesia produced by systemic administration of opiates.

Animals↗
PubMed1979

The origin of descending pathways in the dorsolateral funiculus of the spinal cord of the cat and rat: further studies on the anatomy of pain modulation.

There is considerable evidence that the dorsolateral funiculus (DLF) of the spinal cord contains descending pathways critical for both opiate and brainstem stimulation-produced analgesia. To obtain a comprehensive map of brainstem neurons projecting to the spinal cord via the DLF, large injections of horseradish peroxidase (HRP) were made into the lumbosacral spinal cord of cat and rat. These injections were made caudal to midthoracic lesions which spared only a single DLF or ventral quadrant (VQ); thus only those neurons whose axons descended in the spared funiculus would be labelled. Cells with descending axons in the VQ were concentrated in the medullary nucleus raphe pallidus and obscurus, nucleus retroambiguus and in various subregions of the reticular formation including the nucleus reticularis ventralis, gigantocellularis, magnocellularis, pontis caudalis and pontis oralis. Significant numbers of neurons were also found in medial and lateral vestibular nuclei and in several presumed catecholamine-containing neurons of the dorsolateral pons. In the rat, but not in the cat, considerable numbers of cells are present in the mesencephalic reticular formation just lateral to the periaqueductal gray. In both species, some cells were found in the paraventricular nucleus of the hypothalamus. Brainstem cells projecting in the DLF were concentrated in the nucleus raphe magnus and in the adjacent nucleus reticularis magnocellularis, ipsilateral to the spared funiculus. Significant numbers of cells were found in the dorsolateral pons, differing somewhat in their distribution from those projecting in the VQ. DLF-projecting cells were also present in the ipsilateral Edinger-Westphal nucleus and periaqueductal grey contralateral red nucleus of the midbrain and in the ipsilateral hypothalamus. Smaller projections from other sites are described. These results are discussed in terms of the differential contribution of several brainstem neuronal groups, including the serotonergic nucleus, raphe magnus, the ventromedial reticular formation of the medulla, and various catecholamine-containing neurons of the dorsolateral pontine tegmentum to the analgesia produced by opiates and electrical brain stimulation.

Animals↗
PubMed1979

The posterior pretectal nucleus: evidence for a direct projection to the inferior olive of the cat.

In our horseradish peroxidase (HRP) study of the afferents to the medullary raphe nuclei in the cat, HRP uptake by damaged axons en route to the inferior olive (IO) was thought to be responsible for retrograde labelling of specific midbrain nuclei. To control for such indirect labelling, HRP was injected iontophoretically into the inferior olive. The location of retrogradely labelled neurons was related to the specific locus of HRP injection within the IO. Injection of HRP into the caudal dorsal accessory olive resulted in dense neuronal labelling in the ipsilateral caudal pole of the posterior pretectal nucleus (PPN). There was no labelling of the nucleus of Darkschevitch (Dk), interstitial nucleus of Cajal (ICA) or Edinger-Westphal nucleus (EW). In contrast, an injection focussed more rostrally, into the rostral, dorsal accessory, the medial accessory and the principal olive, produced dense labelling of Dk, ICA and EW; there was much less PPN labelling. It is concluded that labelling of Dk and PPN after HRP injections rostral to the IO, is due, at least in part, to uptake of HRP by damaged medial longitudinal fasciculus axons en route to the inferior olive. The direct PPN-inferior olivary projection provides a potential disynaptic retino-cerebellar connection, which may be involved in rapidly timed eye-body coordinate movements.

Animals↗
PubMed1979

Intradendritic recordings from hippocampal neurons.

Dendritic activity in guinea pig hippocampal CA1 and CA3 pyramidal neurons was examined by using an in vitro preparation. Histologically confirmed intradendritic recordings showed that dendrites had an average input resistance of 47.0 M omega and average membrane time constant of 33.3 msec. Active spike responses could be evoked by intracellular injection of outward current or by the activation of synaptic inputs. The predominant activity was burst firing. A typical intracellularly recorded dendritic burst consisted o spikes on a slowly increasing depolarizing potential. The spike components of the burst were of two distinct types: low threshold, fast spikes; and high threshold, slow spikes. Tetrodotoxin (1 microgram/ml) blocked the fast spikes, but slow spikes could still be evoked with direct intracellular stimulation. In contrast to dendritic responses, direct depolarization of CA1 somata did not give rise to burst generation. Orthodromic stimuli evoked large-amplitude excitatory postsynaptic potentials, followed by inhibitory postsynaptic potentials in dendrites of CA1 and CA3 neurons. In two instances, simultaneous recordings were obtained from coupled pairs of elements that were presumed to be soma and dendrite of the same CA3 pyramidal neuron. Depolarization of either element led to burst generation at that site, and the underlying slow depolarization appeared to evoke a burst at the other site. This potential postsynaptic amplifying mecahnism was not ordinarily functional because even suprathreshold orthodromic activation did not normally evoke bursting in dendrites.

Action Potentials↗
PubMed1978

Endogenous pain control mechanisms: review and hypothesis.

The anatomy, physiology, and pharmacology of an intrinsic neural network that monitors and modulates the activity of pain-transmitting neurons is reviewed. This system can be activated by opiate administration or by electrical stimulation of discrete brainstem sites. Evidence is presented that its pain-suppressing action is mediated in part by endogenous opiatelike compounds (endorphins). This pain suppression system is organized at three levels of the neuraxis: midbrain, medulla, and spinal cord. Activation of neurons in the midbrain periaqueductal gray matter (by electrical stimulation, opiates, and possibly psychological factors) excites neurons of the rostral medulla, some of which contain serotonin. The medullary neurons, in turn, project to and specifically inhibit the firing of trigeminal and spinal pain-transmission neurons. As part of a negative feedback loop, the output of the pain transmission neurons, i.e., pain itself, is an important factor in activating the pain-suppression system. A neural model which incorporates the experimental findings is proposed, and the clinical implications of the model are discussed.

Analgesia↗