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E R Perl

Publications and source records attributed to E R Perl.

At least 37 records · Page 2Linked to original sources
PubMed1994

Differential L-glutamate responsiveness among superficial dorsal horn neurons.

1. Intracellular recordings were made from 128 superficial dorsal horn (laminae I and II) neurons in slice preparations of the lumbosacral spinal cord obtained from young hamsters. Stimulation of the segmental dorsal root evoked postsynaptic potentials in all neurons. The average transmembrane resting potential was -61 +/- 1 mV (mean +/- SE; n = 123). The mean action potential amplitude was 75 +/- 1 mV (n = 105) with a duration at half peak of 1.1 +/- 0.1 ms (n = 102). The mean input resistance of these neurons was 72 +/- 4 M omega (n = 125). These values are comparable to those reported in other studies on neurons of this region using penetrating microelectrodes. 2. Bath application of N-methyl-D-aspartate (NMDA; 50 microM) depolarized 67 of 71 (94%) of the tested neurons. Superfusion with the non-NMDA amino acid agonists DL-alpha-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid (AMPA; 20 microM) and kainate (KA; 50 microM) depolarized all tested neurons by > 10 mV. On the other hand, only 13 of 67 (19%) tested neurons were depolarized > 4 mV by superfusion solutions containing 3 mM L-glutamate (Glu). L-Aspartate at 3 mM depolarized three out of seven neurons by > 4 mV and appeared to be equally as effective as Glu. 3. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM) substantially attenuated the AMPA- and KA-induced depolarizations and partially attenuated the NMDA-induced depolarizations. The NMDA antagonist 3 [(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP; 50 microM) reversibly blocked the NMDA-induced depolarization in all tested neurons. Glu-induced depolarization was unaffected by CNQX but was attenuated by CPP in three of three tested neurons. These observations indicate that some of the Glu-induced depolarization was mediated by NMDA receptors. 4. CNQX reversibly attenuated excitatory postsynaptic potentials (EPSPs) produced by primary afferent activity in A delta- and C-fibers whereas CPP suppressed only the late EPSP components. Therefore in the neurons sampled, synaptic responses evoked from primary afferent fibers appear to be mediated by both non-NMDA and NMDA receptors. 5. The glutamate uptake inhibitors, L-trans-pyrrolidine-2,4-dicarboxylate (L-trans PDC; 50 microM; n = 6) and threo-3-hydroxy-D-aspartate (1 mM; n = 1) did not have a consistent effect upon Glu action background discharge, RN or Vm in Glu-unresponsive neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury.

The mechanisms by which peripheral nerve injuries sometimes lead to causalgia, aberrant burning pain peripheral to the site of nerve damage, are uncertain, although the sympathetic nervous system is known to be involved. Whether such syndromes could be the result of the development of responsiveness by some cutaneous pain receptors (C-fiber nociceptors) to sympathetic efferent activity as a consequence of the nerve injury was tested in an animal model. After nerve damage but not in its absence, sympathetic stimulation and norepinephrine were excitatory for a subset of skin C-fiber nociceptors and enhanced the responsiveness of these nociceptors to tissue-damaging stimulation. These effects were demonstratable within days after nerve lesions, occurred at the cutaneous receptive terminal region, were manifest in sensory fibers that had not degenerated after the injury, and were mediated by alpha 2-adrenergic-like receptors.

Animals↗
PubMed1990

Species-specific expression of cholecystokinin messenger RNA in rodent dorsal root ganglia.

The expression of cholecystokinin (CCK) messenger RNA (mRNA) was examined in dorsal root ganglia of rat and guinea pig using in situ hybridization histochemistry and RNA (Northern) blot hybridization with synthetic oligodeoxyribonucleotide (oligomer) probes. In guinea pig, CCK mRNA was detected in small and medium-sized neuronal perikarya comprising approximately 10-15% of the total dorsal root ganglia cell population. In contrast, in neurons of rat dorsal root ganglia, CCK mRNA was not detectable. Northern blot analyses revealed a single CCK mRNA species of expected size (0.8 kb) in guinea pig, but not rat, dorsal root ganglia. A 0.8 kb CCK mRNA was, however, detected in cortex of both rat and guinea pig. These data suggest that CCK is normally not synthesized in neurons of rat dorsal root ganglia and that there are species differences in CCK gene expression in mammalian sensory ganglia.

Animals↗
PubMed1990

Contributions of arachidonic acid derivatives and substance P to the sensitization of cutaneous nociceptors.

1. The role of presumed chemical mediators of inflammation in the heat-induced sensitization of cutaneous C-polymodal nociceptors (CPNs) was examined in a rabbit ear preparation maintained in vitro by intra-arterial perfusion with a solution free of protein and cellular elements. 2. In this preparation, CPNs consistently showed enhanced responsiveness after repeated exposure of their receptive fields to noxious levels of heat. The average magnitude of sensitization was quantitatively similar to that observed in vivo, suggesting that blood-born factors are not essential for development of sensitization. 3. Sensitization in one-half of randomly selected CPNs was blocked or reduced when the perfusate contained a cyclooxygenase inhibitor, indomethacin or dipyrone, or the dual cyclooxygenase/lipoxygenase inhibitor, BW755C, even though initial responsiveness to heat and pressure was unaltered. These observations suggest that arachidonic acid breakdown products, possibly prostaglandins, are intermediaries in the sensitization of some, but not all, C-fiber nociceptors of the skin. In addition, heat-induced sensitization for some C-fiber cutaneous nociceptors is the result of processes that are at least partially independent of those involved in excitation. 4. Substance P (SP) or the putative SP antagonists, [D-Pro2, D-Trp7.9]-SP or [D-Pro2, D-Phe7, D-Trip9]-SP, produced no significant effect on heat-responsiveness or sensitization, although ongoing activity may have marginally increased over control levels after repeated heat stimulations. We conclude that SP in an in vitro preparation is not involved in the enhancement of cutaneous C-fiber nociceptor responsiveness after repeated thermal insults.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1989

Synaptic ultrastructure of functionally and morphologically characterized neurons of the superficial spinal dorsal horn of cat.

Recordings of neuronal unitary discharges evoked by primary afferent input were made in the superficial part of the spinal cord's dorsal horn, the marginal zone and substantia gelatinosa (also known as laminae I and II), using fine micropipette electrodes filled with HRP. After physiological characterization with respect to primary afferent input, HRP was injected intracellularly iontophoretically into the recorded neuron. Following histochemical processing, the neurons so delineated were studied at the light and electron microscopic levels. No clear relationship between function and either general cellular configuration or synaptic ultrastructure appeared in these analyses, although the concentration of dendritic distribution could be related to the nature of primary afferent excitation. Nocireceptive cells had dendrites mostly branching and ending in lamina I and IIo, while the dendrites of innocuous mechanoreceptive cells arborized principally in lamina II and III. Glomerular synaptic complexes (large, complex arrays of axonic and dendritic profiles with synaptic interconnections) were found to contact a few neurons of both the nocireceptive and mechanoreceptive classes. All neurons received large numbers of simple axonic contacts (small axonic boutons with only 1 or 2 synaptic contacts with a single postsynaptic profile). A degree of specificity in the presynaptic articulations appeared to be reflected by the observations that (1) nocireceptive neurons were never found to receive synaptic contacts from boutons which resembled the known ultrastructure of peripheral innocuous mechanoreceptors, and (2) mechanoreceptive neurons were never seen to receive synaptic contacts from boutons which resembled the known ultrastructure of primary afferent nocireceptors. The axons of the labeled neurons of both nocireceptive and mechanoreceptive classes terminated in simple axonic synapses. All classes of neurons participated in dendrodendritic contacts; however, only some mechanoreceptive neurons had dendrites containing vesicles that were presynaptic to other profiles. No nocireceptive neurons, regardless of gross configuration, were found to have vesicles in their dendrites, but 3 nocireceptive neurons received synapses from presynaptic dendritic profiles.

Afferent Pathways↗
PubMed1988

Reorganization of primary afferent nerve terminals in the spinal dorsal horn of the primate caudal to anterolateral chordotomy.

A primate model has been used to explore the possibility that anterolateral chordotomy may produce intraspinal sprouting or rearrangement of primary afferent nerve terminations that could account for delayed postoperative recovery of sensory function. Monkeys were trained to limit the duration of an electrical stimulus, and the vigor and frequency of their escape responses were used to differentiate painful from nonpainful levels of stimulation. Behavioral testing after chordotomy revealed: 1) contralateral hypalgesia in all animals, with sensory recovery in half of the group, and 2) bilateral decreases in reflexive force in all animals, with reflex recovery in the majority of monkeys. At the terminal experiment, dorsal rootlets caudal to the spinal lesion were labeled bilaterally with HRP, and the distribution of labeled synaptic complexes was determined within the dorsal horn. When compared to controls, animals undergoing chordotomy showed a loss of terminals in the superficial dorsal horn and an increase of synaptic enlargements in deeper layers. These effects were bilateral, but were most pronounced on the side contralateral to chordotomy. Animals with diffuse spinal lesions showed a completely different change in the distribution of primary afferent terminals. Animals with sensory recovery demonstrated a more normal terminal distribution pattern than persistently hypalgesic monkeys, but there was considerable variability in the data, and analysis by different statistical tests yielded varying results.

Afferent Pathways↗
PubMed1988

In situ hybridization using 32P labelled oligodeoxyribonucleotides for the cellular localisation of mRNA in neuronal and endocrine tissue. An analysis of procedural variables.

Methodological variables for in situ hybridization using 32P labelled oligodeoxyribonucleotides (oligomers) have been examined. Four different oligomers directed against proglucagon messenger RNA (mRNA) and two different oligomers against prosomatostatin mRNA have been used. Specific hybridization was obtained in adult rat brain, stomach and pancreas and in neonatal rat ileum. Tissue was perfusion fixed with 4% paraformaldehyde 0.2% glutaraldehyde and hybridization was carried out in 50% formamide for 72 h at 42 degrees C. Using hybridization conditions of lower stringency (33% formamide) labelling was also obtained in guinea pig tissue. Other variables which affected hybridization signal intensity were the inclusion of a prehybridization dehydration stage, the probe concentration, the inclusion of ammonium acetate in the posthybridization dehydrating ethanols and in the autoradiographic emulsion, and the exposure time. The localisation of proglucagon mRNA in rat pancreas using a 20mer was used as a model tissue for testing these methodological variables and the results were found generally also to apply to the other probes and tissues tested. The methods described provide single cell resolution and show that 32P labelled oligomers may be used to localise neuropeptide and endocrine mRNAs in different types of tissue and in different mammalian species.

Animals↗
PubMed1988

Comparison of primary afferent and glutamate excitation of neurons in the mammalian spinal dorsal horn.

The actions of L-glutamate and agonists, agents blocking their membrane receptors and dorsal root afferent volleys, were compared on intracellularly recorded neuronal activity in an in vitro horizontal slice preparation of the hamster spinal dorsal horn. Bath-applied L-glutamate or L-aspartate (less than or equal to 1 mM) rapidly depolarized and excited less than a third of the dorsal horn neurons sampled. Bathing solutions containing low Ca2+ eliminated synaptic transmission in the slices but failed to block the excitatory effects of L-glutamate for the majority of the neurons tested. N-Acetylaspartylglutamate had no effect on dorsal horn neurons at concentrations up to 1 mM. Neurons excited by L-glutamate were most commonly located in the superficial dorsal horn (laminae I and II). Neurons insensitive to L-glutamate were more broadly distributed, with a number being located in laminae III-V. Kynurenic acid, 2-amino-4-phosphonobutyric acid, and 2,3-piperidine dicarboxylic acid selectively antagonized rapid, short-lasting synaptic components of the dorsal cord potentials. Kynurenic acid reversibly antagonized intracellularly recorded L-glutamate-induced excitation, spontaneous synaptic potentials, and fast synaptic potentials evoked by dorsal root volleys. Compounds with strong antagonist actions at the NMDA receptor, 2-amino-5-phosphonovaleric acid and D-alpha-aminoadipic acid, were much less effective in suppressing the effects of L-glutamate or in blocking synaptic potentials. We conclude that a subset of spinal neurons directly excited by dorsal root fibers have excitatory membrane receptors activated by L-glutamate. This conclusion is consistent with the concept that L-glutamate or a substance binding to the receptors it activates is released from the central terminals of some primary afferent fibers and mediates fast synaptic transmission from them to certain spinal neurons in the dorsal horn.

Afferent Pathways↗
PubMed1986

Central projections of identified, unmyelinated (C) afferent fibers innervating mammalian skin.

Unmyelinated (C) fibers are the most numerous sensory elements of mammalian peripheral nerve and comprise many of those responsible for initiating pain and temperature reactions; however, direct evidence has been lacking as to where and how these fibers terminate in the central nervous system. A plant lectin (Phaseolus vulgaris leukoagglutinin) was applied intracellularly by iontophoresis as an immunocytochemical marker. This permitted visualization of the central terminations of cutaneous C sensory fibers that had been identified by the nature of stimuli that excited them. The central branch of C-fiber units arborized and terminated mainly in the superficial layers of the spinal dorsal horn in defined patterns that related to their functional attributes. Thus, the superficial dorsal horn seems to act as a processing station for signals from fine sensory fibers.

Animals↗
PubMed1985

Selective excitation of neurons in the mammalian spinal dorsal horn by aspartate and glutamate in vitro: correlation with location and excitatory input.

The electrical activity of mammalian dorsal horn neurons was recorded with pipette microelectrodes in an in vitro spinal cord slice preparation with dorsal roots intact. Addition of relatively low concentrations of aspartate or glutamate to the superfusion solution or through the recording pipette with small iontophoretic currents excited only a subset of neurons. The majority of these excited neurons were located in the superficial dorsal horn (Rexed's laminae I and II) and a preponderance were excited by the C-fiber components of dorsal root volleys. These findings are consistent with the idea that aspartate or glutamate may function as a synaptic mediator for some neurons terminating in the superficial dorsal horn.

Animals↗
PubMed1985

Functional and morphological features of neurons in the midline region of the caudal spinal cord of the cat.

Neurons surrounding and dorsal to the central canal in caudal segments of the cat spinal cord were functionally and morphologically characterized. From electrophysiologically obtained responses these neurons were categorized into 3 functional groups based on excitation by somatic afferent stimulation. Eighteen of 36 units were activated by both low threshold and high threshold primary afferent inputs. Of the remaining 18 units, 9 responded only to innocuous intensities of stimulation and the other 9 were excited selectively by noxious peripheral stimulation. Neurons intracellularly marked with horseradish peroxidase formed a heterogeneous population with respect to perikaryal size, dendritic orientation and dendritic extent, and no evident correlations between functional categories and morphological features were observed in light microscopic analyses. Neurons immediately surrounding the central canal were functionally similar to neurons located in the dorsally adjacent gray matter.

Animals↗
PubMed1985

Sensory receptors with unmyelinated (C) fibers innervating the skin of the rabbit's ear.

The cutaneous receptive properties of unmyelinated (C) fibers of the rabbit's great auricular nerve were determined by single-unit recordings. The majority of C-fiber units could be excited by cutaneous stimulation, and such sensory units fell into three major categories on the basis of responses to mechanical and thermal stimulation of their cutaneous receptive fields: low-threshold mechanoreceptors, nociceptors, or specific thermoreceptors. The majority of afferent elements were nociceptive, and all nociceptors responded to strong mechanical stimulation. Three types of nociceptors could be distinguished by their responses to thermal stimuli. Polymodal nociceptors responded to heat with thresholds of 40-55 degrees C and typically displayed enhanced responses or sensitization after noxious heating of their receptive fields. High-threshold mechanoreceptors failed to respond promptly to heat before noxious cutaneous stimulation which, however, elicited subsequent back-ground activity or sensitivity to heat. A third type of nociceptor responded to cold but not to heat. Low-threshold mechanoreceptors were identified by their brisk responses to very gentle, slowly moving mechanical stimulation of their receptive fields, and were readily distinguished from any element classified as nociceptive by their lower mechanical thresholds. Rapid innocuous warming or cooling excited some of the low-threshold mechanoreceptors. Specific thermoreceptors, both warming and cooling types, were rare, insensitive to mechanical stimulation, and responded to very slight changes in temperature. In contrast to the sensitization to heat, which was characteristic of most nociceptors, specific warming receptors displayed depressed thermal responses after noxious heating of their receptive fields. These results provide further evidence of the similarity of C-fiber receptors innervating hairy skin of different species. Some differences from past reports and additional features are described.

Afferent Pathways↗
PubMed1985

Regeneration of cutaneous afferent unmyelinated (C) fibers after transection.

The cutaneous receptive properties of C-fiber units were studied 1-8 mo after transection and repair of the rabbit's great auricular nerve. The proportions of C-fiber units that could be excited by the cutaneous stimuli known to excite normal C-fiber afferent elements of the same nerve increased with time of recovery and approached the normal range within 5 mo after transection. No evidence was obtained that suggests that any specific receptor type regenerated more rapidly than others. No differences were established between the cutaneous receptive properties of normal and regenerated low-threshold mechanoreceptors or specific thermoreceptors. However, the properties of regenerated polymodal nociceptors were different from those of normal polymodal nociceptors. Mechanical thresholds for regenerated polymodal nociceptors were greater than normal at 2 mo after transection but not later, and nearly 20% of regenerated polymodal units had heat thresholds lower than normal. It is argued that the abnormal properties of some regenerated polymodal nociceptors could explain, in part, the elevated thresholds to noxious mechanical stimulation and the thermal hyperalgesia reported during recovery from nerve transection in man.

Afferent Pathways↗
PubMed1985

Failure of sympathetic stimulation to affect responsiveness of rabbit polymodal nociceptors.

The responses of polymodal nociceptors with unmyelinated (C) fibers of the rabbit's great auricular nerve were examined with and without intermittent stimulation of the ipsilateral cervical sympathetic trunk. The receptive field of each polymodal nociceptor was heated twice in a stepwise manner from 30 to 50 or 55 degrees C in 5 degree C steps. For each unit, one heating trial was a control trial and the other was accompanied by sympathetic stimulation. The order of the control and sympathetic stimulation trials and the maximum testing temperature were varied systematically among the units examined. The initial responses of polymodal nociceptors in the first heating trial in the presence of sympathetic stimulation were similar to the responses of units whose first heating was a control trial. Units whose receptive fields were tested to a maximum temperature of 50 degrees C in the first trial displayed enhanced responses to heat in their second trial (sensitization), while units tested initially to 55 degrees C responded less briskly during their second heating trial (depression). However, the occurrence of sympathetic stimulation in the second heating trials had no apparent effect on the responses to heat of sensitized or depressed elements. Alterations in the numbers of impulses, instantaneous frequency, or pattern of impulse activity of individual units could not be attributed to sympathetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Is ATP a central synaptic mediator for certain primary afferent fibers from mammalian skin?

The possibility that ATP acts as a synaptic mediator at the central terminals of primary afferent fibers was examined by applying it iontophoretically to neurons of the outer layers of the cat spinal cord in vivo. ATP proved to be selectively excitatory for a limited subset of spinal neurons. Those units consistently excited by ATP iontophoresis with very small currents (2-15 nA) responded to gentle mechanical stimulation of the skin and usually evidenced excitatory input from unmyelinated primary afferent fibers. Most units excited by ATP were specifically mechanoreceptive; a few neurons receiving excitatory input from both low-threshold mechanoreceptors and nociceptors also responded to ATP. Selectively nocireceptive neurons were unresponsive. Generally, the mechanoreceptive neurons excited by ATP were located in the deeper substantia gelatinosa or in the immediately adjacent nucleus proprius of the dorsal horn. The results suggest the presence of a purinergic excitatory receptor on central neurons receiving excitatory projection from tactile mechanoreceptors with fine-diameter afferent fibers and are consistent with the possibility that an ATP-like agent may mediate central synaptic excitation for this set of sense organs.

Adenosine Triphosphate↗
PubMed1984

Morphology and synaptic relationships of physiologically identified low-threshold dorsal root axons stained with intra-axonal horseradish peroxidase in the cat and monkey.

The arborizations and synaptic relationships of intra-axonally stained horseradish peroxidase- (HRP) labeled primary afferent fibers to the dorsal horn of the cat and monkey spinal cord have been studied by light and electron microscopic methods. The light microscopic arborizations of the afferent fiber types (hair follicle afferents, pacinian corpuscle afferents, type I and type II slowly adapting afferents) are similar to those described by Brown and his colleagues (1) in the cat. The synaptic profiles formed by labeled afferents contain rounded synaptic vesicles. In serial thin sections, it was found that single dorsal root axons may make hundreds or thousands of synapses with neuronal structures of the dorsal horn. The vast majority of synaptic contacts are on the dendritic trees of dorsal horn neurons. The synapses made by these low-threshold afferent axons are almost all in the deeper laminae (III-VI) of the dorsal horn. The hair follicle afferent axons and the pacinian corpuscle afferents have numerous vesicle-containing structures that synapse on them to form either axoaxonal synapses or dendroaxonal synapses. The slowly adapting afferent axons are less often found to be postsynaptic to axons or dendrites. It is concluded that different physiological classes of primary afferent axons have different morphological characteristics, both at the light and electron microscopic level.

Afferent Pathways↗