Search PubMed⌕ Search

Biomedical subjects

A I Basbaum

Publications and source records attributed to A I Basbaum.

At least 163 records · Page 9Linked to original sources
PubMed1986

Immunoreactive glutamic acid decarboxylase in the trigeminal nucleus caudalis of the cat: a light- and electron-microscopic analysis.

This study used antisera directed against glutamic acid decarboxylase (GAD), the biosynthetic enzyme for gamma-aminobutyric acid (GABA), to examine the light- and electron-microscopic distribution of presumed GABA-ergic synapses in the medullary homologue of the cat spinal dorsal horn, the trigeminal nucleus caudalis. At the light-microscopic level, immunoreactive terminals were concentrated in the superficial dorsal horn, laminae I and II. Colchicine was generally ineffective in revealing the distribution of cell bodies. However, in two successful cases, the majority of labeled cells were found in the magnocellular layer, ventral to the substantia gelatinosa, a region that had a lower density of immunoreactive terminals. Other labeled neurons were scattered in laminae I and II. A variety of synaptic arrangements were found at the electron-microscopic level. These derived from two types of labeled terminals. One contained both small round vesicles and large dense-cored vesicles. The second contained small round and pleomorphic vesicles. Some immunoreactive GAD terminals contained a few flat vesicles. Labeled terminals predominantly formed axodendritic synapses, via symmetrical contacts. Several axoaxonic arrangements were also observed. In most cases, the GAD terminal (which did not contain dense-cored vesicles) was presynaptic to another vesicle-containing profile, including the scalloped central terminal thought to derive from primary afferents. Another population of labeled GAD terminals was found postsynaptic to unlabeled vesicle-containing profiles, including central terminals. These data indicate that inhibitory GABA-ergic controls in the trigeminal nucleus caudalis involve both presynaptic and postsynaptic mechanisms and are probably mediated via direct contacts onto ascending projection neurons, as well as via synaptic contacts onto nociceptive primary afferent fibers. The transmission of nociceptive messages by neurons of the spinal cord dorsal horn and trigeminal nucleus caudalis is subject to a variety of segmental and supraspinal controls. Pharmacological and electrophysiological studies have implicated the biogenic amines serotonin and norepinephrine, and the endogenous opioid peptides enkephalin and dynorphin, in those controls (Basbaum and Fields, 1978, 1984; Basbaum et al., 1983; Basbaum, 1985).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Immunoreactive dynorphin B in sacral primary afferent fibers of the cat.

Immunocytochemical analysis of the distribution of dynorphin B terminals in the sacral spinal cord of the cat revealed a pattern of staining very similar to that produced with antisera directed against the primary afferent derived, putative neurotransmitter, vasoactive intestinal polypeptide. Labeled axons and terminals were concentrated in lamina I and V and there was dense fiber staining in the tract of Lissauer. Of particular interest was the presence of immunoreactive axons in attached dorsal rootlets. To specifically focus on the possibility that some of the sacral primary afferent fibers are dynorphin-immunoreactive, we first tried to increase perikaryal labeling in the sacral dorsal root ganglia by topical treatment with colchicine. This did not produce immunoreactive labeling of cell bodies in the ganglia. Unilateral multiple dorsal rhizotomy (L5 to coccygeal 1), however, significantly decreased the staining of dynorphin-immunoreactive axons and terminals in the tract of Lissauer and in the dorsal horn of sacral segments ipsilateral to the deafferentation. No changes were detected in the lumbar cord. Finally, radioimmunoassay of caudal lumbar and sacral dorsal root ganglia was performed. Measurable immunoreactivity was found in all ganglia assayed, but, consistent with the histochemical analysis, sacral ganglia contained the highest concentration of immunoreactive dynorphin B. These data indicate that a significant component of the sacral spinal cord dynorphin terminal immunoreactivity derives from primary afferent fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Clinical response to regional intravenous guanethidine in patients with rheumatoid arthritis.

A novel therapy for rheumatoid arthritis, regional sympathetic blockade using guanethidine, was investigated in 24 patients with active disease. In a randomized double blind short-term (14 days) study, we evaluated the effect of therapy on subjective responses, change in pain, stiffness, and morning stiffness and no objective responses, change in pinch strength, grip strength, and joint tenderness. Compared to placebo, guanethidine produced a decrease in pain (p less than 0.025) and an increase in pinch strength (less than 0.025) over the 2-week duration of the study. The therapeutic effect of guanethidine may be mediated by an interruption of the proinflammatory effects of the sympathetic nervous system.

Anti-Inflammatory Agents↗
PubMed1986

Contribution of sensory afferents and sympathetic efferents to joint injury in experimental arthritis.

We used pharmacological and surgical methods to determine the contribution of several neural components to joint injury in rats with adjuvant-induced arthritis. Both neonatal administration of capsaicin, which eliminates small-diameter afferents, and peripheral sympathectomy, which depletes catecholamines, attenuated joint injury. In contrast, the arthritis was more severe in spontaneously hypertensive rats, which have increased sympathetic tone. To address the contribution of the central vs peripheral afferent terminal selectively, a group of rats underwent unilateral dorsal rhizotomy. These rats developed a more severe arthritis in the deafferented limb. The increase in arthritis severity produced by dorsal rhizotomy could be reduced by prior sympathectomy or, less effectively, by prior treatment with capsaicin. The latter observation suggests that large-diameter afferents that are cut during dorsal rhizotomy also influence inflammation. Finally, intracerebroventricular injection of morphine attenuated the severity of arthritis, possibly through activation of bulbospinal sympathoinhibitory circuits. Taken together, these data indicate that no one class of nerve fiber is wholly responsible for the neurogenic component of inflammation in experimental arthritis but that large- and small-diameter afferents, sympathetic efferents, and CNS circuits that modulate those fiber systems all influence the severity of joint injury in arthritic rats.

Animals↗
PubMed1985

Multiple opioid peptides and the modulation of pain: immunohistochemical analysis of dynorphin and enkephalin in the trigeminal nucleus caudalis and spinal cord of the cat.

Using immunocytochemistry, we have identified important differences in the distribution of immunoreactive dynorphin and enkephalin cells and terminals in the trigeminal nucleus caudalis and in the spinal dorsal horn of the cat. Dynorphin immunoreactive processes are more closely associated with those regions of cord that process nociceptive information, specifically laminae I and V. Enkephalin neurons and terminals are more widespread. Based on the staining pattern with an antiserum to the octapeptide-metenkephalin-arg-gly-leu, we suggest that the dense enkephalin terminal immunoreactivity in the inner part of the substantia gelatinosa derives from cells in lamina III. There are also significant differences in the anatomical relationship of the two opioid peptides with the organization of parasympathetic autonomic preganglionic neurons. The functional significance of these observations must await physiological analysis; nevertheless, it is almost certain that differences will be found and that these will be important in understanding the mechanisms through which exogenous opiates and a variety of descending control systems exert their effects on spinal cord neurons.

Animals↗
PubMed1985

Identification of Aplysia neurons containing immunoreactive FMRFamide.

Electrophysiological and immunocytochemical techniques were used in the abdominal ganglion of Aplysia to identify neurons containing immunoreactive FMRFamide. Large numbers of neurons were immunoreactive for FMRFamide, including R2, L2, L3, L4, L5, L6, 2 cells tentatively identified as L12 and L13, and a previously unidentified cluster on the ventral surface of the right lower quadrant. There was also heavy labelling of fibers, often with beaded varicosities, throughout the neuropil, the cell layers, and the sheath overlying the ganglion. This data provides further evidence that FMRFamide is an important neurotransmitter in Aplysia. The demonstration of immunoreactive FMRFamide in the giant cholinergic neurons R2 and LP1(1) suggests that these well-studied and experimentally convenient cells use acetylcholine and an FMRFamide-like peptide as cotransmitters.

Animals↗
PubMed1985

The contribution of neurogenic inflammation in experimental arthritis.

The release of the peptide neurotransmitter substance P from the peripheral terminals of nociceptive afferent neurons and the release of catecholamines from postganglionic sympathetic efferent neurons produce physiologic changes associated with acute inflammation. The contribution of these neurogenic mechanisms to inflammatory diseases has not been determined. Activation of central neural circuits elicits similar physiologic changes, and lesions of the peripheral and central nervous system are associated with alteration in activity of inflammatory diseases. We have evaluated the contribution of neurogenic inflammation to the severity of joint injury in experimentally induced arthritis in the rat. The finding of a greater density of substance P-containing nociceptive afferents in a joint that develops more severe arthritis (ankle) suggests a role of substance P in joint injury. Direct evidence that the proinflammatory factor released from these nociceptors is substance P is provided by the finding that the injection of substance P into a joint which normally develops less severe arthritis (knee) increases the severity of arthritis in that joint. A contribution of catecholamines to the severity of joint injury was suggested by the finding that both guanethidine-induced sympathectomy and reserpine-induced depletion of catecholamines attenuated the severity of joint injury. Finally, a contribution of central neural circuits to inflammatory processes was studied in a model in which activation of nociceptive afferents elicited swelling and tenderness at a remote site. This reflex neurogenic inflammation was inhibited by intracerebroventricular injections of morphine, which also attenuated the severity of arthritis. These studies provide evidence that elements of the peripheral afferent and sympathetic efferent neurons and of descending supraspinal, opioid-mediated, circuits in the central nervous system modulate the severity of joint injury in experimental arthritis in the rat.

Animals↗
PubMed1985

Hypothesis: the nervous system may contribute to the pathophysiology of rheumatoid arthritis.

No current theory of the mechanisms involved in the pathophysiology of rheumatoid arthritis (RA) explains its important clinical features. We hypothesize that neural mechanisms are involved in this pathophysiology and they explain at least 3 clinical features: specific high risk joints are more likely to develop arthritis; specific high risk joints have more severe arthritis; and RA is bilaterally symmetric. If our hypothesis is correct, it will provide a rationale for the development of new therapies for what is now an inadequately treated disease.

Arthritis, Rheumatoid↗
PubMed1985

Reflex neurogenic inflammation. I. Contribution of the peripheral nervous system to spatially remote inflammatory responses that follow injury.

Recent studies of the mechanism of neurogenic inflammation have focused on the contribution of neuropeptides released from peripheral terminals of primary afferent sensory neurons. In this study we addressed the contribution of humoral and neural factors to the hyperalgesia and swelling that are produced contralateral to an injured hindpaw, a phenomenon which we refer to as reflex neurogenic inflammation. The contralateral inflammatory response develops gradually, over a period of hours, and shows no tachyphylaxis with repeated application of the same stimulus. Denervation of either limb significantly attenuated the contralateral responses. Selective lesions of small-diameter, presumed nociceptive afferent fibers with capsaicin, or of sympathetic postganglionic efferents by immunosympathectomy, also reduced swelling and hyperalgesia of the uninjured paw. Interruption of venous circulation to the injured limb by vein ligation did not alter the response in the contralateral paw. Taken together, these data suggest that reflex neurogenic inflammation is neurally mediated, via connections across the spinal cord.

Animals↗
PubMed1984

Immunoreactive pro-enkephalin and prodynorphin products are differentially distributed within the nucleus of the solitary tract of the rat.

In this study we examined the distribution of two different endogenous opioid peptides in the nucleus of the solitary tract of the rat medulla. As a marker for immunoreactive enkephalin, we used an antiserum directed against one of the proenkephalin products, methionine enkephalin-arg-gly-leu (m-Enk). To identify immunoreactive dynorphin we used an antiserum directed against the prodynorphin product, dynorphin B (Dyn B). The PAP method was used on both colchicine and normal animals. Caudal to the obex, within the commissural nucleus, there is extensive overlap of both immunoreactive m-Enk and Dyn B terminals and cells. While the cells are morphologically similar, the immunoreactive dynorphin cells are somewhat larger. Rostral to the obex, there is a marked difference in the distribution of the two compounds. Immunoreactive m-Enk terminals are concentrated medial to the solitary tract; there is minimal staining laterally. In contrast, immunoreactive Dyn B terminals are concentrated lateral to the solitary tract. The rostral cellular distribution of the two opioid peptides follows a similar pattern. The morphology of the medially located m-Enk and laterally located Dyn B cells is also readily distinguished. The former are small, round cells with minimal dendritic labelling; the latter are larger, pyramidal neurons with prominent apical and basal dendrites. Since the medial and lateral nuclei of the solitary tract have been associated with cardiovascular and respiratory control, respectively, these data suggest that different endorphin families have different functional actions within the nucleus of the solitary tract.

Animals↗
PubMed1984

Intraneuronal substance P contributes to the severity of experimental arthritis.

There is evidence that substance P is a peptide neurotransmitter of some unmyelinated primary afferent nociceptors and that its release from the peripheral terminals of primary afferent fibers mediates neurogenic inflammation. The investigators examined whether substance P also contributes to the severity of adjuvant-induced arthritis, an inflammatory disease in rats. They found that, in the rat, joints that developed more severe arthritis (ankles) were more densely innervated by substance P-containing primary afferent neurons than were joints that developed less severe arthritis (knees). Infusion of substance P into the knee increased the severity of arthritis; injection of a substance P receptor antagonist did not. These results suggest a significant physiological difference between joints that develop mild and severe arthritis and indicate that release of intraneuronal substance P in joints contributes to the severity of the arthritis.

Animals↗
PubMed1984

Axons which take up [3H]serotonin are presynaptic to enkephalin immunoreactive neurons in cat dorsal horn.

Through combined ultrastructural localization of ENK immunoreactivity and [3H]5-HT uptake sites, it was found that 5-HT radiolabeled axons contact ENK immunoreactive cell bodies and small dendrites in the cat superficial dorsal horn. While some contacts displayed both pre- and postsynaptic specializations, the majority lacked a definitive synaptic cleft and postsynaptic density. These results suggest that 5-HT-containing axons, presumably derived from the medullary nucleus raphe magnus, directly influence spinal opiod antinociceptive activity.

Afferent Pathways↗
PubMed1984

Colocalization of immunoreactive proenkephalin and prodynorphin products in medullary neurons of the rat.

This study addressed the possible coexistence of products of the proenkephalin and prodynorphin opioid peptide precursors in single neurons of the central nervous system of the rat. Antisera directed against met-enkephalin-arg-gly-leu and against Dyn B were used in immunohistochemical preparations of sections through the rat medulla. Examination of serial three micron frozen sections stained alternately with the two different antisera revealed that the majority of labelled neurons stain with only one of the two antisera. In specific area, however, immunoreactive m-enk and Dyn B could be detected in the same neuron. This was particularly true of the caudal ventrolateral nucleus of the solitary tract, where the two peptides were colocalized in most neurons. Other areas where the two peptides coexist include the midline raphe and the nucleus reticularis paragigantocellularis. These data provide the first evidence for colocalization of different opioid peptide families in single CNS neurons.

Animals↗
PubMed1984

Radioimmunocytochemistry using a tritiated goat anti-rabbit second antibody.

Affinity-purified goat anti-rabbit immunoglobulin G (GAR) was conjugated with (3H)-propionyl succinimidate and used to localize substance P (SP), enkephalin (ENK), and serotonin immunoreactive sites in the spinal dorsal horn and medulla of the rat and cat. Autoradiographic localization was demonstrated on paraffin, frozen, Vibratome, and 2 micron plastic sections. The latter were obtained from radiolabeled Vibratome sections that were embedded in epoxy resin. The distribution of SP, ENK, and serotonin demonstrated by radioimmunocytochemistry was comparable to that observed on semiadjacent sections using peroxidase-antiperoxidase (PAP) immunocytochemistry. The autoradiograms, however, were generated using primary antibody concentrations up to five times more dilute than concentrations used for the PAP procedure. Indirect radioimmunocytochemistry using a (3H) anti-immunoglobulin G second antibody can be used to localize a variety of monoclonal and polyclonal antisera. It is quantifiable at the light microscopic level and can be potentially used with peroxidase histochemistry to double label immunoreactive structures at the ultrastructural level.

Animals↗
PubMed1983

The fine structure of the caudal periaqueductal gray of the cat: morphology and synaptic organization of normal and immunoreactive enkephalin-labeled profiles.

Although the midbrain periaqueductal gray (PAG) is thought to have a major role in an endorphin-mediated analgesia system, little is known about its neuroanatomical organization. To determine the microcircuitry within the PAG through which exogenous and endogenous opiates may act, we analyzed the synaptic organization of normal and immunoreactive enkephalin (ENK)-labeled profiles in the caudal PAG, a region of particular interest because of its effectiveness in generating analgesia. Examination of the normal fine structure of this region demonstrated that there is no characteristic synaptic morphology that distinguishes individual regions of the caudal PAG (ventromedial, ventrolateral and dorsolateral) from one another. In all 3 regions of the caudal PAG, axodendritic synapses are the predominant form of synaptic interaction making up 93-97% of all synapses counted. Axosomatic synapses are much less common, as are presumed axoaxonic and dendrodendritic synapses. In the caudal ventral PAG, the largest population of ENK-labeled axonal boutons are found presynaptic to unlabeled, centrally placed dendrites. Much less frequently, immunoreactive ENK-containing boutons are found presynaptic to neuronal perikarya or vesicle-containing profiles. Thus, these results suggest that the dendrites of neurons intrinsic to the PAG are the most probable site of opiate action in the caudal ventral PAG.

Animals↗
PubMed1983

Opioid neurons and pain modulation: an ultrastructural analysis of enkephalin in cat superficial dorsal horn.

To clarify the circuitry through which opioid compounds modulate spinal and trigeminal nociceptive transmission, we have examined the synaptic associations formed by leucine-enkephalin-containing (enkephalin) neurons in the superficial dorsal horn of the cat. As described previously, punctate enkephalin immunoreactivity is concentrated in the marginal layer (lamina I) and in both the outer and inner layers of the substantia gelatinosa (lamina IIo and IIi). In colchicine treated cats, enkephalin perikarya are most numerous in lamina I and at the border between laminae I and II. Ultrastructural analysis reveals that enkephalin cells receive a diverse afferent input. The majority of afferent inputs are presynaptic to the enkephalin dendrites; few axosomatic synapses are seen. Among these presynaptic axonal profiles are unlabeled axons which resemble primary afferent terminals, including the characteristic central axonal varicosity. Enkephalin dendrites are also postsynaptic to enkephalin immunoreactive axons. Two types of enkephalin axonal profiles appear in the superficial dorsal horn. Class I profiles are only found in lamina I. These are large profiles which form few synapses; those synapses made are axodendritic. Class II enkephalin axons are smaller and are distributed in both layers I and II. While Class II axons most commonly form axo-dendritic synapses, they also form axo-axonic synapses with flat vesicle-containing profiles; the latter are generally presynaptic to the enkephalin terminals. Serial analysis further revealed that both the enkephalin and the flat vesicle-containing profile synapse onto a common dendrite. Although enkephalin axons frequently lie adjacent to round vesicle-containing profiles, anatomical evidence that opioid axons form synapses with this type of ending was not found. An additional type of enkephalin vesicle containing-profile is found in layer IIi; its morphological features do not clearly distinguish its axonal or dendritic origin. These endings are typically postsynaptic to unlabelled central endings, and provide minimal presynaptic input to other elements in the neuropil. Like some class II axons, these labelled profiles contain vesicles which cluster at the membrane immediately adjacent to unlabelled central axons. These results indicate that spinal enkephalin neurons receive a variety of synaptic inputs. These include inputs which may derive from primary afferent axons. Enkephalin neurons, in turn, influence nociceptive transmission predominantly through postsynaptic mechanisms. Finally, while we did not observe enkephalin terminals presynaptic in an axoaxonic relationship, the possibility that enkephalin neurons modulate the excitability of fine fiber nociceptive and nonnociceptive afferents via "nonsynaptic interactions" is discussed.

Animals↗
PubMed1983

Immunoreactive vasoactive intestinal polypeptide is concentrated in the sacral spinal cord: a possible marker for pelvic visceral afferent fibers.

Previous descriptions of immunoreactive vasoactive intestinal polypeptide (VIP) in small-diameter dorsal root ganglion cells in the superficial dorsal horn implicated this 28 amino acid peptide in nociceptive transmission. In this study, we examined the distribution of immunoreactive VIP in the spinal cord and caudal medulla of cats and rats. The PAP method was used on paraffin and frozen sections of 4% paraformaldehyde-fixed tissue, using antibodies to VIP that were raised in rabbits. The distribution of immunoreactive VIP, while similar to that of substance P (SP), a putative primary afferent peptide neurotransmitter, is more restricted. VIP staining is found in sacral dorsal roots and densely in the Lissauer tract. Dorsal horn staining is concentrated in lamina I. In contrast to SP, lamina II is almost devoid of staining. Labeled VIP axons course along the lateral curvature of the dorsal horn and arborize across lamina V and around the central canal. A collateral branch of these fibers distributes to the sacral autonomic nucleus. A few fibers could be traced from the root entry zone to the contralateral central gray. VIP axons also terminate between ependymal cells of the central canal. Unlike SP, immunoreactive VIP was restricted, almost exclusively, to the sacral cord. The few fibers in the lumbar enlargement and in the coccygeal cord apparently derive from ascending and descending sacral primary afferents. In fact, the VIP pattern is almost identical to that reported for afferents from the pelvic viscera, including a discontinuous rostrocaudal distribution. Since the staining pattern is also very similar to that of A-delta high-threshold mechanoreceptors, the possibility is discussed that whereas VIP is not a general "somatic" primary afferent transmitter, it may transmit nociceptive input from the pelvic viscera.

Afferent Pathways↗